The present invention relates to an aqueous dispersion comprising a solid pulverulent component A and an aqueous component B, said component A comprising a UV-curable powder coating material.

The present invention relates to an aqueous dispersion of UV-curable powder coating materials which are applied to substrates and then, following partial or complete evaporation of the water and heating to form a film of the powder particles, are cured by means of high-energy radiation, preferably UV light, to give crosslinked coating films. They are particularly suitable for auto bodies made of sheet metal and/or plastic, applied by means of electrostatically assisted high-speed rotation or pneumatically, as a coating for car bodies coated with waterborne basecoat.
Liquid coating materials are presently used with preference for the coating of car bodies. Such materials give rise to numerous environmental problems owing to their solvent content. This also applies to the use of waterborne coating materials.
It is for this reason that increased efforts have been made in recent years to use powder coating materials for the coating. The result to date, however, have not been satisfactory; in particular, increased coat thicknesses are necessary in order to obtain a uniform appearance.
Further serious problems of powder coating materials for thermal curing arise from the requirement for blocking resistance on storage and storability even in summer temperatures. In order to ensure that this requirement is met, the softening point of the coating powders must be high. Because of the high softening point of the coating materials, however, the heat-activated crosslinking reaction begins prematurely during the melting of the powders on the substrate, before the film surface has achieved optimum leveling. To solve this problems, UV-curable powder coating materials are proposed in which it is possible to separate the melting operation from the crosslinking. The UV powder coating materials which have been disclosed to date are all based on substances containing acrylic or vinylic unsaturation, which owing to the high melting temperature required for good blocking resistance can also undergo thermal polymerization prior to UV irradiation. In order to guarantee blocking resistance, the binders employed for the UV powder coating materials must be absolutely solvent-free polymers, which are highly problematic to obtain owing to their tendency to undergo thermal polymerization.
A further problem with the use of powder coating materials is that they cannot be used on existing plants designed for liquid coating materials, because of the different application technology. This was the spur to the development of powder coating materials in the form of aqueous dispersions which can be processed using liquid coating technologies. Examples of the publications in this field are DE 196 13 547.8-43 and DE 195 18 392.4.
U.S. Pat. No. 4,268,542, for example, discloses a process which uses a powder coating slurry that is suitable for the coating of cars. In this process, a conventional powder coat is first applied to the bodywork, and the transparent coating slurry is applied as a second coat. This transparent coating slurry, based on acrylate resins, uses ionic thickeners which result in relatively high sensitivity of the applied coating film to moisture, especially to condensation. Furthermore, in one of the examples these contain from 0.5 to 30% of glycidyl-containing monomers. Moreover, it is necessary to operate with high stoving temperatures (more than 160xc2x0 C.).
However, the general problem of heat-activated crosslinking when the water is evaporated off and the resultant covering of powder coating material is melted is still not always solved using this technology, since crosslinking does not start at a sharply defined temperature but instead starts gradually, before the water has fully evaporated and an optimum surface has formed. Following the onset of the crosslinking reaction, water still emerging as a result of the high temperatures required is the cause of bubbles and craters.
In the text below, the terms transparent powder coating dispersion and transparent powder coating material are used synonymously.
It is an object of the present invention to provide an aqueous dispersion, comprising a solid pulverulent component A and an aqueous component B, which can be applied to car bodies by means of the conventional liquid coating technology and which is UV-curable.
We have found that this object is achieved when component A comprises a UV-curable powder coating material.
The technical advantages of the dispersion of the invention lie in the possibility of using UV powder coating materials having a markedly lower softening point than in the case of dry application, since the particles in the dispersion are unable to cake together. This lower softening temperature results in surfaces which exhibit good flow and are retained since it is not necessary to heat them to high xe2x80x9cstovingxe2x80x9d temperatures for the purpose of crosslinking. It has in fact been found, completely surprisingly, that UV curing, with a minimal residual water content of the melted film, takes place particularly quickly and completely. Accordingly, the natural equilibrium between the water content in the film and in the ambient air, which is dependent on the hydrophilicity of the crosslinking coating films, is quickly established as early as during cooling. A further important advantage is the energy saving due to the lower drying and melting temperatures.
Since the UV powder coating dispersions are self-crosslinking systems, the homogenization of binder, crosslinker and additives by means, for example, of extrusion is not absolutely necessary, in contradistinction to thermally crosslinking powder coating materials.
Suitable UV-curable powder coating materials are the binders known from the prior art. Particularly suitable are acrylate resins having lateral functional groups such as, for example, epoxy groups or hydroxyl groups, with molecular weights in the range from Mn 1000 to 10,000 with molecular weight distributions  less than 4, as are described, for example, in DE 4203278, which are subsequently reacted with acrylic acid or acrylic acid derivatives, such as acryloyl chloride, to give the corresponding acrylated acrylates (EP 650979).
Functional resins which can be employed are preferably those containing aliphatic compounds. For example, epoxy-containing binders with a glycidyl-containing monomer content of from 5 to 45% by weight, preferably from 25 to 40% by weight, are suitable.
Copolymers containing epoxy groups can be prepared either with acrylic acid, methacrylic acid or mixtures of these. It is likewise possible to use mixtures of acrylic acid, methacrylic acid and (meth)acrylic anhydride.
Particularly suitable are the acrylate resins that are described in DE 203278 and have lateral functional groups, e.g. epoxy groups or hydroxyl groups, which are preferably reacted with acrylic acid or acrylic acid derivatives, e.g. acryloyl chloride, to give the corresponding acrylated acrylates (cf. EP 650 979).
Examples of suitable epoxy-functional binders for the solid transparent powder coating material are polyacrylate resins which contain epoxy groups and are preparable by copolymerization of at least one ethylenically unsaturated monomer which contains at least one epoxy group in the molecule with at least one further ethylenically unsaturated monomer which contains no epoxy group in the molecule, at least one of the monomers being an ester of acrylic acid or methacrylic acid. Polyacrylate resins of this kind, containing epoxy groups, are known, for example, from EP-A-299 420, DE-B-22 14 650, DE-B-27 49 576, U.S. Pat. No. 4,091,048 and U.S. Pat. No. 3,781,379.
Examples of ethylenically unsaturated monomers which contain no epoxy group in the molecule are alkyl esters of acrylic and methacrylic acid containing 1 to 20 carbon atoms in the alkyl radical, especially methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate and 2-ethylhexyl methacrylate. Further examples of ethylenically unsaturated monomers which contain no epoxy groups in the molecule are acid amides, such as acrylamide and methacrylamide, maleamide (MAA), vinylaromatic compounds such as styrene, methylstyrene and vinyltoluene, nitriles, such as acrylonitrile and methacrylonitrile, vinyl halides and vinylidene halides, such as vinyl chloride and vinylidene fluoride, vinyl esters, such as vinyl acetate, and hydroxyl-containing monomers, such as hydroxyethyl acrylate and hydroxyethyl methacrylate.
The epoxy-functional monomers employed in the epoxy-functional binders are preferably glycidyl acrylate, glycidyl methacrylate, allyl esters and allyl glycidyl ether.
The polyacrylate resin containing epoxy groups typically has an epoxide equivalent weight of from 400 to 2500, preferably from 420 to 700, a number-average molecular weight (determined by gel permeation chromatography using a polystyrene standard) of from 2000 to 20,000, preferably from 1000 to 10,000, and a glass transition temperature (Tg) of from 30 to 80, preferably from 40 to 70 and, with particular preference, from 40 to 60xc2x0 C. (measured by means of Differential Scanning Calorimetry (DSC)). About 50xc2x0 C. is very particularly preferred. The molecular weight distributions lie preferably below 6, with particular preference below 3. Suitable acrylate resins are described, for example, in DE 203278. It is also possible to employ mixtures of two or more acrylate resins.
The polyacrylate resin containing epoxy groups can be prepared by polymerization in accordance with methods which are generally well known.
In addition, the functional resins may also feature aromatic compounds. The proportion of such compounds should be below 30%, preferably below 20%. They can, for example, comprise vinylaromatic compounds. An example of such is styrene.
In addition, it is possible to employ:
unsaturated polymers of a wide variety of polymer types with 0.5-3.5 double bonds per 1000 molar weight, which are obtained by polymer-analogous reaction of polymers with unsaturated substances (DE 24 36 186).
Polymethacrylates of low molecular weight (500-2500) and narrow distribution, which are obtained by anionic polymerization and are functionalized by polymer-analogous reaction with double bonds (U.S. Pat. No. 4,064,161).
Blends of solid epoxy acrylates by reaction of diepoxy resins with acrylic acid and partially crystalline solid polyester acrylates from carboxyl-terminated polyester by reaction with glycidyl acrylates (U.S. Pat. No. 4,129,488).
Unsaturated polyurethane acrylates with a melting range of 50-180xc2x0 C. (EP 410 242).
Blends comprising unsaturated polyurethane acrylates with unsaturated crystalline polyesters for improving the blocking resistance (EP 585 742).
Blends of unsaturated polyesters or polyacrylates with polyurethane vinyl ether (EP 636 669).
Functional polyacrylates formed from olefinically unsaturated monomers by reaction of functionally complementary polyacrylates (EP 650 978).
Embodiment relating to EP 650 978, in which the base polymers are prepared in a high-temperature polymerization (EP 650 985).
Double-bond-free polyacrylates are crosslinked by way of H transfer to photochemically excited, copolymeric photoinitiators of the Norrish type II (DE 44 13 436).
Double-bond-free polyacrylates comprising dihydro-dicyclopentadienol acrylate are crosslinked by way of H transfer to photochemically excited, copolymeric photoinitiators of the Norrish type II (DE 196 00 147).
Further systems for binders A:
PCT/EP 96/05769 crosslinked polymeric compounds having at least one ethylenic double bond with organic compounds containing at least one hydrogen atom having a bond energy of max. 397 kJ/mol.
PCT/EP97/07074 discloses a process for preparing radiation-crosslinkable acrylate polymers by polymer-analogous reaction of polyacrylates with substances which introduce a group which forms free radicals with actinic radiation.
Component A can comprise one or more of the substances mentioned. Their preparation can take place in accordance with the methods specified there, without the selection of component A being restricted to substances from these documents.
The photoinitiators required for UV crosslinking are generally present in components A and are in general selected from the substances known from the prior art. Polymers according to DE 44 13 436 and DE 196 00 147 are UV-curable without added photoinitiators. Particularly well-crosslinked films are obtained using components A which comprise mixtures of unsaturated polymers and polymers according to DE 44 13 436 and DE 196 00 147 having a particularly high proportion of photochemically excitable, copolymeric photoinitiators of Norrish type II, which in this case function as polymeric photoinitiators.
The component A can consist of unitary binders or of blends of different binders, in which not all of the constituents need be UV-crosslinkable. It may also be advantageous to use UV-curable binders in combination with heat-curable binders; in this case, interpenetrating networks having particularly advantageous film properties are formed.
In addition, component A can comprise crosslinkers, so that the photochemical curing may be supplemented by thermal crosslinking as well.
Suitable crosslinkers are carboxylic acids, especially saturated, straight-chain, aliphatic dicarboxylic acids having 3 to 20 carbon atoms in a molecule. Very particular preference is given to the use of 1,12-dodecanedicarboxylic acid. To modify the properties of the finished transparent powder coating materials it is possible, if desired, to employ other carboxyl-containing crosslinkers. As examples of these, mention may be made of saturated branched or unsaturated straight-chain dicarboxylic and polycarboxylic acids and also polymers having carboxyl groups.
Also suitable, furthermore, are transparent powder coating materials which comprise an epoxy-functional crosslinker and an acid-functional binder.
A further example comprises tris(alkoxycarbonylamino)-triazines in accordance with U.S. Pat. No. 4,939,213, U.S. Pat. No. 5,084,541 and EP 0 624 577.
These documents relate to tris(alkoxycarbonylamino)-triazines of the formula
in which R denotes methyl, butyl or ethylhexyl groups. It is likewise possible to employ derivatives of said compounds.
In accordance with the invention, preference is given to the methyl/butyl mixed esters. These have the advantage over the pure methyl esters of improved solubility in polymer melts relative to butyl/ethylhexyl mixed esters. In accordance with the invention, preference is also given to the pure butyl esters.
The tris(alkoxycarbonylamino)triazines and their derivatives can also, in accordance with the invention, be employed in a mixture with conventional crosslinking agents (component C). Particularly suitable in this case are blocked polyisocyanates which differ from the tris(alkoxycarbonylamino)triazines. It is also possible to employ amino resins, examples being melamine resins.
In principle it is possible to employ any amino resin suitable for transparent topcoats, or a mixture of such amino resins.
Resins of this kind are well known to the skilled worker and are offered by numerous companies as commercial products. Amino resins are condensation products of aldehydes, especially formaldehyde, with, for example, urea, melamine, guanamine and benzoguanamine. The amino resins contain alcohol groups, preferably methylol groups, some or all of which are generally etherified with alcohols. Otherwise, it is also possible to use any other suitable crosslinking agent known from the prior art, examples being blocked polyfunctional isocyanates.
Examples of suitable acid-functional binders are acidic polyacrylate resins, which are preparable by copolymerizing at least one ethylenically unsaturated monomer containing at least one acid group in the molecule with at least one further ethylenically unsaturated monomer which contains no acid group in the molecule.
The binder which contains epoxy groups and the crosslinker which contains epoxy groups, respectively, and the carboxyl-containing binder and the carboxyl-containing crosslinker, respectively, are typically employed in amounts such that there are from 0.5 to 1.5, preferably from 0.75 to 1.25, equivalents of carboxyl groups per equivalent of epoxy groups. The amount of carboxyl groups present can be determined by titration with an alcoholic KOH solution.
In accordance with the invention, the binder can comprise vinylaromatic compounds, especially styrene. In order to limit the danger of cracking, however, the amount is preferably not more than 35% by weight. From 10 to 25% by weight are preferred.
The solid powder coating materials comprise, if desired, one or more suitable catalysts for the epoxy resin curing. Suitable catalysts are phosphonium salts of organic or inorganic acids, quaternary ammonium compounds, amines, and imidazole and imidazole derivatives. The catalysts are generally employed in proportions of from 0.001% by weight to about 2% by weight, based on the overall weight of the epoxy resin and of the crosslinking agent.
Examples of suitable phosphonium catalysts are ethyltriphenylphosphonium iodide, ethyltriphenylphosphonium chloride, ethyltriphenylphosphonium thiocyanate, ethyltriphenylphosphonium acetate/acetic acid complex, tetrabutylphosphonium iodide, tetrabutylphosphonium bromide and tetrabutylphosphonium acetate/acetic acid complex. These and other suitable phosphonium catalysts are described, for example, in U.S. Pat. No. 3,477,990 and U.S. Pat. No. 3,341,580.
Examples of suitable imidazole catalysts are 2-styrylimidazole, 1-benzyl-2-methylimidazole, 2-methylimidazole imidazole and 2-butylimidazole. These and other imidazole catalysts are described, for example, in Belgian Patent No. 756,693.
In addition, the solid powder coating materials may, if desired, comprise auxiliaries and additives. Examples of these are leveling agents, antioxidants, UV absorbers, free-radical scavengers, flow aids and degassing agents, such as benzoin, for example.
The solid powder coating materials are prepared by known methods (cf., for example, product information from the company BASF Lacke + Farben AG, xe2x80x9cPulverlackexe2x80x9d, 1990) by homogenizing and dispersing, for example by means of an extruder, screw-type kneading machine and the like. After their preparation, the powder coating materials are prepared for dispersing by grinding and, if desired, by sieving and classifying.
To prepare the dispersion, component A is dispersed in an aqueous component B. Accordingly, the continuous phase is preferably water. If desired, component B contains further components by means of which the powder coating materials of the invention are dispersed and the dispersion is stabilized. By means of further auxiliaries it is possible to produce the required performance properties. Component B may comprise ionic and/or nonionic monomeric and/or polymeric surfactants and protective colloids. Selection here takes place taking into account the technical requirements in relation to the cured films. It has been found advantageous to use polymeric substances which are chemically similar to the components A and which are able to undergo co-crosslinking with the binders present in the components A in the course of UV curing. For the dispersion of the invention, substances of this kind are, for example, based on polyacrylates. They are preferably polyacrylate protective colloids which are obtained from (meth)acrylates by copolymerization with (meth)acrylic acid and in which some of the carboxyl groups are reacted with glycidyl (meth)acrylate and some more have been neutralized with nitrogen bases.
Also particularly suitable are double-bond-free binders in accordance, for example, with DE 44 13 436 and/or DE 196 00 147, which have been polymerized with fractions of (meth)acrylic acid and then neutralized, in whole or in part, with nitrogen bases. Preference is also given in accordance with the invention to the use of binderlike dispersants which have basic groups and have been (partly) neutralized with acids. An advantage of the present invention is to be able to choose freely between both cationic and anionic stabilization forms and, for example, to be able to choose the most cost-effective method or the method which is easy to conduct chemically without having to take account of the chemistry of the crosslinking reaction. For example, the binders according to DE 44 13 436 and DE 196 00 147 are inert with respect to the majority of chemical reactions and are crosslinked only by means of high-energy radiation. Such systems can then be applied to various substrates by conventional powder slurry techniques and can be cured at elevated temperature (above the melting temperature of the resin) by UV radiation or electron beams.
Polyurethane protective colloids which are particularly suitable for the dispersion of the invention based on polyurethanes are those which are obtained from isocyanates, polyols, hydroxycarboxylic acids and hydroxy(meth)acrylates and/or hydroxyvinyl ethers and are (wholly or partly) neutralized with nitrogen bases. Said protective colloids have a good dispersing action and in many cases also a desired thickening action, and are co-crosslinked with the melted powder particles in the course of UV curing, thereby resulting in extremely weather-resistant coatings.
Also suitable, however, are commercially available substances, such as anionic and cationic soaps, nonionic surfactants based, for example, on polyoxyethylene/propylene block polymers or on polyoxyethylene-fatty acid esters. Also suitable are polyvinylpyrrolidone protective colloids and polyvinyl alcohol protective colloids which have a good stabilizing and thickening action. The selection, and, if appropriate, combination of different substances is an optimization task with which the skilled worker is familiar and which takes place in each individual case in accordance with the requirements relating to the dispersion in terms, for example, of pumpability, flow behavior, viscosity or storage conditions, or in accordance with the requirements relating to the cured coating material in respect, for example, of weather resistance, overcoatability, gloss and intercoat adhesion.
The binders can be pigmented or unpigmented or, respectively, be provided with or without dyes. Preference, however, is given to unpigmented binders for the preparation of transparent powder coating materials.
As a further essential constituent the aqueous component B of the powder coating dispersion comprises at least one nonionic thickener a). Preference is given to the use of nonionic associative thickeners a). This is so in particular when pH values of 4-7 are to be observed.
Structural features of such associative thickeners a) are:
aa) a hydrophilic structure which ensures adequate solubility in water, and
ab) hydrophobic groups, which are capable of associative interaction in the aqueous medium.
Examples of hydrophobic groups employed are long-chain alkyl radicals, such as dodecyl, hexadecyl or octadecyl radicals, or alkaryl radicals, such as octylphenyl or nonylphenyl radicals, for example.
Hydrophilic structures preferably employed are polyacrylates, cellulose ethers or, with particular preference, polyurethanes, which contain the hydrophobic groups as polymer units.
Very particular preference as hydrophilic structures is given to polyurethanes which contain polyether chains as units, preferably comprising polyethylene oxide.
In the synthesis of such polyether polyurethanes, the di- and/or polyisocyanates, preferably aliphatic diisocyanates and, with particular preference, unsubstituted or alkyl-substituted 1,6-hexamethylene diisocyanate, are used to link the hydroxyl-terminated polyether units with one another and to link the polyether units with the hydrophobic end-group units, which may, for example, be monofunctional alcohols and/or amines bearing the long-chain alkyl radicals or aralkyl radicals already mentioned.
The powder coating dispersion may additionally comprise dispersing auxiliaries. Examples include aryl polyglycol ethers and octylphenol ethoxylates (in part hydrogenated).
The dispersing auxiliaries which can be employed with preference in component B include polyurethanes, inter alia.
These can consist preferably of
1. at least one organic component having at least two reactive hydrogen atoms,
2. a monofunctional ether, and
3. a polyisocyanate.
The organic component of the polyurethane composition comprises a polyester polyol, a low molecular mass diol and/or triol, or mixtures thereof. If desired, a trifunctional hydroxyl-containing monomer can be employed.
In a second preferred embodiment the polyurethane comprises
1. at least one organic component having at least two reactive hydrogen atoms,
2. a nonionic stabilizer which is prepared by reacting
I. a monofunctional polyether with a polyisocyanate component to produce an isocyanate intermediate and
II. a component having at least one active amine group and at least two active hydroxyl groups, and
3. at least one polyisocyanate component.
The organic component preferably comprises polyether/polyester polyol, a low molecular mass diol and/or triol, or mixtures thereof.
The polyester component can be prepared by reacting at least one dicarboxylic acid and at least one alcohol component, the alcohol comprising at least two hydroxyl groups. The carboxylic acid component comprises two or more carboxyl groups.
In addition to the carboxylic acids the polyester resin can also comprise one or more low molecular mass diols or triols. In principle, any polyol can be employed.
The polyester resins or mixtures of polyester resins employed comprise preferably terminal hydroxyl groups. This is brought about by adding an excess of polyols.
For the synthesis of the polyesters it is possible to employ both monocarboxylic acids and monoalcohols. Preferably, however, the monocarboxylic acids and/or monoalcohols are present in a very small amount by weight in the polyester resin.
The polyester diol components employed with preference comprise between 20 and 80% by weight of the polyurethane resin. The amounts are preferably between 50 and 70% by weight. Very particular preference is given to from 55 to 65% by weight.
The polyurethane is prepared employing polyester polyols having a molecular weight of between 500 and 5000. Preference is given to molecular weights of between 1000 and 3500.
In addition to the polyester diols, the polyurethane resins can comprise further organic components having at least two reactive hydrogen atoms. These are preferably diols and triols, thiols and/or amines, or mixtures of these substances. The components used to synthesize the polyester component can also be employed here as separate components. In other words, dialcohols or trialcohols, such as neopentyl glycol or 1,6-hexanediol, for example, are also suitable as an additional organic component in the polyurethane.
The molecular weight of the diols and/or triols employed in the polyurethane resin is between 0 and 20% by weight. Preference is given to from 1 to 6% by weight.
The polyurethane resin additionally comprises polyisocyanates, especially diisocyanates. The isocyanates are present at between 5 and 40% by weight based on the polyurethane mass. Particular preference is given to from 10 to 30% by weight and very particular preference to from 10 to 20% by weight. To prepare the polyurethane, finally, a monofunctional polyether is employed.
In a second variant, a nonionic stabilizer is prepared by, preferably, reacting a monofunctional polyether with a diisocyanate. The resultant reaction product is then reacted with a component which comprises at least one active amine group and at least two active hydroxyl groups.
In one particular embodiment the polyurethane comprises a reaction product of:
1. a polyester polyol, which is in turn a reaction product of a carboxylic acid having at least two carboxyl groups and a component having at least two hydroxyl groups,
2. at least one low molecular mass component having at least two hydroxyl groups,
3. at least one polyisocyanate component,
4. a nonionic stabilizer prepared by reacting a monofunctional ether with a polyisocyanate and then reacting the resultant reaction product with a component which comprises at least one active amine group and at least two active hydroxyl groups.
In a fourth variant, the polyurethane comprises a reaction product of
1. a polyester polyol,
2. at least one low molecular mass diol or triol,
3. a polyisocyanate,
4. a trihydroxyl-containing monomer,
5. a monofunctional hydroxyl-containing polyether.
The polyesters are synthesized using the above-described carboxylic acid components and an excess of polyols. The excess of polyols is chosen so that preferably terminal hydroxyl groups are formed. The polyols preferably have a hydroxyl functionality of at least two.
The polyester resin consists preferably of one or more polyols, preferably comprising one diol. Diols employed with preference are alkylene glycols, such as ethylene glycol, propylene glycol, butylene glycol and neopentyl glycol, 1,6-hexanediol or other glycols, such as bisphenol A, cyclohexanedimethanol, caprolactonediol, hydroxyalkylated bisphenol, and similar compounds.
The low molecular mass diols which are preferably employed in accordance with the invention are known from the prior art. They include aliphatic diols, preferably alkylene polyols having 2 to 18 carbon atoms. Examples of such are 1,4-butanediol and cycloaliphatic diols, such as 1,2-cyclohexanediol and cyclohexanedimethanol.
Suitable organic polyisocyanates in accordance with the invention are preferably those which comprise at least two isocyanate groups. Particular preference is given to diisocyanates, e.g. p-phenylene diisocyanate, biphenyl 4,4xe2x80x2-diisocyanate, toluene diisocyanates, 3,3xe2x80x2-dimethyl-4,4xe2x80x2-biphenylene diisocyanate, 1,4-tetramethylene diisocyanate, 1,6-hexamethylene diisocyanate, 2,2,4-trimethylhexane 1,6-diisocyanate, methylenebis-(phenyl isocyanates), 1,5-naphthalene diisocyanate, bis(isocyanatoethyl fumarate), isophorone diisocyanate and methylenebis(4-cyclohexyl isocyanate).
In addition to the abovementioned diisocyanates, other multifunctional isocyanates are also used. Examples are 1,2,4-benzene triisocyanate and polymethylenepolyphenyl isocyanates.
Particular preference is given to the use of aliphatic diisocyanates, examples being 1,6-hexamethylene di-isocyanate, 1,4-butylene diisocyanate, methylene-bis(4-cyclohexyl isocyanate), isophorone diisocyanate and 2,4-toluene diisocyanate.
Relatively long-chain polyurethane resins can be obtained by chain extension with components containing diol and/or triol groups. Particular preference is given to chain extenders having at least two active hydrogen groups, examples being diols, thiols, diamines and mixtures of these substances, e.g. alkanolamines, aminoalkyl mercaptans, hydroxyalkyl mercaptans, and similar compounds.
Examples of diols employed as chain extenders are 1,6-hexanediol, cyclohexanedimethylol and 1,4-butanediol. A particularly preferred diol is neopentyl glycol.
The polyethers which can be employed are preferably mono- or difunctional polyethers. The monofunctional ones include, for example, those prepared by polymerizing ethylene oxides, propylene oxides or mixtures thereof.
The polyurethane product described can be mixed with conventional crosslinkers. These include preferably amino resins, e.g. melamine. It is also possible to employ condensation products of other amines and amides, e.g. aldehyde condensates of triazines, diazines, triazoles, guanadines, guanamines or alkyl- and aryl-substituted derivatives of such components. Some examples of such components are N,Nxe2x80x2-dimethylurea, dicyandiamide, 2-chloro-4,6-diamino-1,3,5-triazine, 6-methyl-2,4-diamino-1,3,5-triazine, 3,5-diamino-triazole, triaminopyrimidines, 2-mercapto-4,6-diamino-pyrimidine, 2,4,6-triethyltriamino-1,3,5-triazine and similar substances.
The preferred aldehyde is formaldehyde. It is also possible to employ acetaldehyde, crotonaldehyde, acrolein, benzaldehyde and furfural.
The amine-aldehyde condensation products can comprise methylol or similar alcohol groups. Examples of alcohols which can be employed are methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, benzyl alcohol and aromatic alcohols, cyclic alcohols, such as cyclohexanol, monoethers or glycols, and also substituted alcohols, e.g., 3-chloropropanol.
In addition to the abovementioned isocyanates it is also possible to employ blocked polyisocyanates as crosslinking agents. Examples of these include organic polyisocyanates such as trimethylene, tetramethylene, hexamethylene, 1,2-propylene, 1,2-butylene and 2,3-butylene diisocyanates. Further candidates for use include cycloalkane components such as 1,3-cyclopentane, 1,4-cyclohexane and 1,2-cyclohexane diisocyanates. It is also possible to use aromatic components such as phenylene, p-phenylene, 4,4xe2x80x2-diphenyl, 1,5-napthalene and 1,4-naphthalene diisocyanates. Components suitable in addition to these are aliphatic-aromatic components such as 4,4xe2x80x2-diphenylenemethane, 2,4- or 2,6-tolylene, or mixtures thereof, 4,4xe2x80x2-toluidine and 1,4-xylylene diisocyanates. Further examples are ring-substituted aromatic components such as 4,4xe2x80x2-diphenyl ether diisocyanates and chlorodiphenylene diisocyanates. Triisocyanates which can be employed are triphenyl-methane 4,4xe2x80x2,4xe2x80x3-triisocyanate, 1,3,5-triisocyanatobenzene and 2,4,6-triisocyanatotoluene. A tetraisocyanate which can be used, finally, is 4,4xe2x80x2-diphenyl-dimethylmethane 2,2xe2x80x2,5,5xe2x80x2-tetraisocyanate.
Blocking agents which can be employed include aliphatic, cycloaliphatic and aromatic alkyl monoalcohols. Examples of these include methyl, ethyl, chloroethyl, propyl, butyl, cyclohexyl, heptyl, octyl, nonyl (including 3,3,5-trimethylhexanol), decyl and lauryl alcohols. Examples of phenolic components which can be used are phenols or substituted phenols. Examples thereof are cresol, xylenol, nitrophenol, chlorophenol, ethylphenol, 1-butylphenol and 2,5-di-tert-buty-4-hydroxytoluene.
Further suitable blocking agents are tertiary hydroxylamines, e.g. diethylethanolamine, and oximes, such as methyl ethyl ketone oxime, acetone oxime and cyclohexanone oxime.
The crosslinking agents described are present in the polyurethane dispersion in amounts from 2 to 15% by weight, preferably from 4 to 8% by weight.
The polyurethane obtained can be present in the powder slurry in a proportion of from 2 to 20% by weight, preferably from 5 to 15% by weight.
One particularly preferred embodiment relates to nonionic (associative) thickeners which are able to react photochemically with themselves and/or with the other binders A, so further improving the coating properties. Photochemically active nonionic thickeners can be obtained by incorporating double bonds or groups having readily abstractable hydrogen atoms, such as dicyclopentadienyl groups and/or photoinitiator groups of the Norrish II type, especially benzophenone groups.
The aqueous dispersion of transparent powder coating material can be prepared from the components A and B by wet grinding or by stirred incorporation of the dry-ground powder coating material present in component A. Particular preference is given to wet grinding.
The present invention also provides a process for preparing an aqueous dispersion of powder coating material on the basis of the above-described component A, which in accordance with the invention is dispersed in a component B. The latter consists of an aqueous dispersion of catalysts, auxiliaries, antifoams, antioxidants, wetting agents, UV absorbers, free-radical scavengers, biocides, water retention agents, and small amounts of solvents and/or dispersing auxiliaries, preferably carboxy-functional dispersing auxiliaries.
The acrylated acrylate resins can then be dispersed with the abovementioned dispersing auxiliaries by grinding to an average particle size of a few xcexcm.
Particular preference is given to the wet grinding of a preliminary dispersion. To this end, prior to or following the substances B and further auxiliaries, the coating powders are dispersed in water using, for example, a high-speed dissolver. It is also possible first of all to add only some of substances B and auxiliaries and to meter in the remainder prior to or following subsequent dispersion and/or wet grinding. In certain cases the preliminary dispersion can be processed directly; in general, it is subjected to secondary grinding in appropriate mills, e.g., stirred ball mills, in order to establish the desired particle fineness. After the dispersing operation, the dispersion is ground, if desired, to a desired particle size spectrum and, if desired, the pH is adjusted to the level determined as a function of the system, and the resultant dispersion is filtered. A special advantage of the invention in comparison to powder coating materials is that even a very fine particle size spectrum can be processed, e.g. 1-3 xcexcm, a level at which powder coating materials can no longer be applied, with the result of a surface quality (evenness) which cannot be achieved using powders.
Following the dispersion of component A in component B, the pH is adjusted preferably to 4.0 to 7.0 and, with particular preference, to 5.5 to 6.5.
The average particle size is between 1 and 200 xcexcm, preferably below 20 xcexcm and, with particular preference, from 2 to 10 xcexcm. The solids content of the aqueous dispersion of transparent powder coating material is between 15 and 50%.
Before or after the wet grinding or the introduction of the dry powder coating material into the water, it is possible to add to the dispersion from 0.5% by weight of a defoamer mixture, an ammonium salt and/or alkali metal salt, a carboxy-functional or nonionic dispersing auxiliary, wetting agent and/or thickener mixture, and the other additives. Preferably, in accordance with the invention, defoamers, dispersing auxiliaries, wetting agents and/or thickeners are first of all dispersed in water. Then small portions of the transparent powder coating material are stirred in. After that, defoamers, dispersing auxiliaries, thickeners and wetting agents are dispersed into the mixture once again. Finally, small portions of transparent powder coating materials are stirred in again.
In accordance with the invention, the pH is preferably adjusted using amines, especially in the case of anionically stabilized dispersions. In this context the pH may initially increase, so that a strongly basic dispersion is formed. Within several hours or days, however, the pH falls again to the values indicated above.
Also possible, however, are the dispersions stabilized cationically in the manner described above, where the pH is established using acids, preferably volatile carboxylic acids.
The dispersion of transparent powder coating material according to the invention can be used as a coating over basecoats, preferably in the automotive industry. The dispersion of transparent coating material is particularly suitable for waterborne basecoats based on a polyester, polyurethane resin and an amino resin.
Suitable substrates are all surfaces to be coated that are amenable to UV curing; in other words, for example, metals, plastics, wood, ceramic, stone, textiles, fiber composites, leather, glass, glass fibers, glasswool and rockwool, mineral-bound and resin-bound building materials, such as plasterboards and cement boards, and also roof tiles, and especially auto bodies. Dispersions of transparent powder coating material according to the invention are specifically suitable as coating over basecoats, preferably in the automotive industry. They are particularly suitable as clearcoats over waterborne basecoats based on polyesters, polyurethane resins and amino resins.
The UV powder coating dispersions applied to the substrates are first of all subjected to extensive preliminary drying prior to UV curing. This preliminary drying takes place at room temperature or, in accelerated form, at elevated temperature. The elevated temperature is generally from 40 to 70xc2x0 C., preferably from 50 to 65xc2x0 C. Preliminary drying is carried out for from 2 to 10 minutes, preferably from 4 to 8 minutes. Thereafter, the temperature is raised to the melting temperature of the resin particles, and, after a smooth surface has formed, crosslinking is carried out with high-energy radiation, preferably UV light. It is also possible to dispense with the preliminary drying and to carry out drying and melting in one step in a temperature program. A great advantage of the invention can be seen in that exposure at temperatures of 90 to 120xc2x0 C. can be carried out at a level considerably below the typical stoving temperatures of from 140 to 180xc2x0 C. At the low exposure temperature, water still present in the film does not interfere with curing and causes no boil marks or craters. The equilibrium between atmospheric moisture and film, which is a function of the material, is then established within a short time, as with all coatings.
The dispersions of transparent powder coating material according to the invention can be applied using the methods known from liquid coating technology. In particular, they can be applied by means of spraying techniques. Also suitable are electrostatically assisted high-speed rotation or pneumatic application.
With the process of the invention it is possible to obtain coat thicknesses of from 10 to 60, preferably from 20 to 60 and, with particular preference, from 20 to 50 xcexcm, very preferably from 25 to 45 xcexcm. In accordance with the prior art, coatings of comparable quality could previously be achieved only by applying coat thicknesses of from 65 to 80 xcexcm when using transparent powder coating materials.

Aqueous dispersion of transparent powder coating material


The present invention is directed to a pharmaceutical composition, preferably in the form of a tablet comprising a therapeutically effective amount of a medicament in a carrier comprising a water insoluble polymer and a water-insoluble inorganic salt.

The present invention relates to a formulation of a water insoluble controlled release carrier to provide controlled release of medicaments.
Sustained or slow release compositions containing pharmaceutical medicaments or other active ingredients are designed to contain higher concentrations of the medicament and are prepared in such a manner as to effect sustained or slow release into the gastro-intestinal digestive tract of humans or animals over an extended period of time. Well absorbed oral sustained or slow release therapeutic drug dosage forms have inherent advantages over conventional, immediate release dosage forms. The advantages include less frequent dosing of a medicament and resultant patient regime compliance, a more sustained drug blood level response, therapeutic action with less ingested drug and the mitigation of side effects. By providing a slow and steady release of the medicament over time, absorbed drug concentration spikes are mitigated or eliminated by effecting a smoother and more sustained blood level response.
For this purpose, a controlled release formulation has to meet some criteria; namely it must effect an uniform and constant dissolution of the drugs and it must be effective for an extended period of time. It is also important that such a formulation be simple to make, that the manufacturing process be reproducible and that the product produced by the manufacturing process be uniform. Moreover, if different drugs are used as the active component in the sustained released formulation, it is important that the manufacturing process be easily adaptable to accommodate these various drugs.
To prepare sustained release formulations in the form of a solid oral dosage, such as tablets, various hydrophilic as well as hydrophobic polymers have been utilized. Materials such as waxes have also been used. Formulations made using many of these materials not only offer different release characteristics, but also have several disadvantages associated therewith. For example, the wax matrices are unstable towards heat which can cause sudden release of the drug from the dosage form. On the other hand, the hydrophilic matrices provide sustained release by forming a gel as a protective barrier, which has proven to be an effective method for controlling drug release. However, the swelling of hydrophilic polymers is often affected by the ionic environment of the gastrointestinal tract, which may affect the release rate. Sometimes failure of the matrix has also been observed. Because the hydrophilic matrices swell and erode over a period of time, they can not provide a constant surface area for the release of the drug and in some cases, where the solubility thereof in water is high and the concentration of the drug in the dosage form is very high, they fail to offer controlled release over a long period of time. Thus, there is a need to find a system which does not suffer from these disadvantages.
Various methods such as solvent evaporation, heat melting, direct compression as well as wet granulation have been used to prepare sustained release pharmaceuticals. The only methods which are practical for industrial manufacture of such matrices are direct compression and wet granulation.
Various hydrophobic polymers have been used for fabrication of controlled release matrices. These polymers are elastic and often have poor flow characteristics, thus making them quite unsuitable for commercial manufacture. It is also necessary that the polymer particles coalesce to form an insoluble matrix in order to control the release of the active agent; very high concentrations are often needed. Wet granulation using solutions of such polymers in organic solvents tends to be difficult because solutions containing high polymer content tend to be viscous; therefore to achieve an effective amount of polymer concentration, large amounts of organic solvent are needed. However, many organic solvents are toxic and are quite volatile and flammable, thereby exposing the chemist or other persons directly involved in the manufacture thereof to health and safety hazards. Moreover, multiple granulation procedures are often required.
Aqueous dispersions of such polymers have also been used for wet granulation. Once again multiple granulations are needed to obtain effective amounts of the polymer in the tablet. Unfortunately, high polymer concentration also creates difficulties in granulation by forming rubbery masses.
Mulye, et al. in Drug Development and Industrial Pharmacy, 20(17), 2621-2632 (1994) disclose a matrix formulation in the form of a tablet comprising a highly water soluble drug, i.e., chlorpheniramine maleate (xe2x80x9cCPMxe2x80x9d), bromopheniramine maleate, dextromethorphanxe2x80xa2HBr, procainexe2x80xa2HCl, diphenhydraminexe2x80xa2HCl, theophylline and niacinamide. These tablets contained, in addition, dicalcium phosphate dihydrate (DCPD) or Eudragit and optionally magnesium stearate. This publication discloses that Eudragit is virtually ineffective in controlling the release profile. It also showed that DCPD was more effective than the Eudragit in controlling the release of the water soluble drug, such as CPM, but that the DCPD containing matrix had a major limitation; when the drug concentration was greater than 5% by weight, the tablet disintegrated.
Mulye, et al., in Drug Development and Industrial Pharmacy, 20(17), 2633-2643 (1994) continued the study described hereinabove. In this paper, Mulye, et al. prepared a tablet containing CPM, DCPD and Eudragit. Their study showed that the addition of Eudragit did not affect the drug release profile relative to that obtained with CPM and DCPD in the absence of Eudragit. It was postulated that the hydrophobic polymer had difficulty binding with the hydrophilic surface of the drug, and it was thus ineffective in reducing the release rate. However, when a plasticizer, such as diethylphthalate was added, there was a significant decrease in release rate. These study showed that a plasticizer was required to be present with the DCPD to release the drug in a controlled manner.
However, the present inventor searched for a system wherein a plasticizer was not a necessary component. The present inventor has found such a system.
The present inventor has also overcome the inadequacies of the prior art and is able to prepare a tablet containing the drug and DCPD wherein the drug is present in a concentration greater than 5% by weight. More specifically, he has found a means of preparing a formulation matrix comprising the drug, the hydrophobic salt and a hydrophobic polymer in which the drug is present in greater than 5% by weight.
The present inventor has found that by utilizing a water insoluble inorganic salt in combination with a water insoluble polymer in a ratio within a certain range in the carrier system of the sustained release formulation, the formulation does not suffer from the disadvantages described hereinabove.
The present invention is directed to a pharmaceutical composition comprising a therapeutically effective amount of a medicament and a controlled release carrier, such carrier comprising a water insoluble polymer and a water insoluble inorganic salt, both being present in a sufficient amount to interact with the drug and form a water insoluble barrier thereover sufficient to retard the release of the medicament in aqueous medium, e.g., the gut, said polymer being present from about 1% up to about 50% by weight of the carrier and said inorganic salt being present from about 1% up to about 95% by weight of the carrier, wherein said carrier is present in an amount ranging from about 1% to about 95% by weight of the composition, and said medicament is present in greater than 5% by weight of the composition.
The present invention utilizes a combination of a water insoluble inorganic salt and a hydrophobic polymer to provide a controlled release pharmaceutical composition whereby the active ingredient or medicament is present in amounts greater than 5% by weight.
The controlled release formulation of the present invention is to be administered to mammals in need of such treatment wherein the medicament present in the formulation is administered in effective amounts. By mammals it is meant a vertebrae of the class Mammalia, that is characterized by possession of hair and mammary glands. Examples include, inter alia, dog, cat, horse, pig, goat, cow, and human beings. The preferred species of mammal to which the sustain release formulation of the present invention is to be administered is man.
The dosage form is prepared by conventional techniques, such as by using wet granulation techniques employing either an organic solvent as a granulating medium when the polymer is used in powder form or an aqueous dispersion of the polymer. This procedure offers a one step granulation procedure using minimal, and often no organic solvents, thereby reducing the exposure of the chemist thereto. This formulation technique also permits the use of significantly low concentrations of the polymer.
Thus the invention relates to a pharmaceutical formulation of a water insoluble matrix comprising an inorganic salt and a hydrophobic polymer, said matrix essentially maintaining its integrity and shape while the drug is being released. The dosage form is comprised of a medicament and a controlled release carrier comprising a water insoluble polymer and an inorganic salt in the amounts described hereinabove. The present inventor has found that the inorganic salt when used in conjunction with the water insoluble polymer in the above concentrations facilitates the formation of the pharmaceutical composition and helps maintain its integrity and stability, even when the drug is present in concentrations higher than 5% by weight. Heretofore, as described hereinabove, dicalcium phosphate dihydrate matrices alone, without the insoluble polymer, could not maintain drug integrity at drug concentrations of higher than 5% by weight; when the drug was present in concentrations greater than 5% by weight, the compositions fell apart. However, the present inventor has found that the combination of the water-insoluble organic salt and water insoluble hydrophobic polymer in the amounts described herein permits the formation of the drug formulation and stabilizes the drug formulation, even at drug concentrations greater than 5% by weight. Furthermore, the inventor found that even if the drug is highly water soluble, such as chlorpheniramine maleate, the addition of such polymers did not significantly retard the release of the drug, as did dicalcium phosphate dihydrate in the absence of such polymer, even when the concentration of the drug was less than 5% by weight. Moreover, the inventor has found that the combination in the ratios provided permits the drug to be released in a controlled release manner in an amount more effective than when dicalcium phosphate dihydrate is used alone.
The first component of the pharmaceutical composition of the present invention is the water insoluble polymer. By water insoluble, it is meant that the polymer is substantially or completely water insoluble at 25xc2x0 C. It is preferred that the polymer has a solubility in water of less than about 0.001 g/l at 25xc2x0 C. The polymer is preferably an organic polymer. Suitable water insoluble polymers are those that are pharmaceutically safe and non-toxic. Examples include methyl methacrylate polymer (EUDRAGIT), ethyl cellulose, cellulose acetate, polyvinyl acetate, polyvinyl chloride, polystyrene, and the like. The preferred polymer is methyl methacrylate copolymer.
The first component is present in the carrier in amounts ranging from about 1% to about 50% (w/w). It is preferred that the water insoluble polymer is present in at least 1% of the carrier up to about 20% (w/w) of the carrier. It is also preferred that it is present from about 1% up to about 20% and more preferably from about 1% to about 15% by weight of the pharmaceutical composition, it is even more preferred that it is present in about 3% to about 15% (w/w) and most preferably from about 4% to about 10% (w/w) of the pharmaceutical composition. Moreover, it is preferred that the weight ratio of drug to polymer is greater than about 3:1 and more preferably greater than about 5:1. It is preferred that the weight ratio ranges from about 5:1 to about 20:1 and more preferably from about 6:1 to about 15:1.
The second component of the present invention is a pharmaceutically acceptable water insoluble inorganic salt. Again, it is preferred that the solubility of the inorganic salt in water at 25xc2x0 C. is less than about 0.001 g/l. Moreover, the inorganic salt is non-toxic and pharmaceutically safe.
It is preferred that the inorganic salt is a salt of a calcium salt, magnesium salt, or zinc salt. Examples of inorganic salts suitable for the present invention are dicalcium phosphate, calcium sulfate, tricalcium phosphate, calcium carbonate, magnesium carbonate, zinc carbonate and the like. The more preferred inorganic salt is a calcium salt. The even more preferred inorganic salts are sulfate and especially phosphate salts of calcium. The most preferred inorganic salts are tricalcium phosphate, and especially dicalcium phosphate.
The inorganic salt is present from about 1% to about 95% by weight of the carrier. It is preferred that it is present in at least 50% by weight of the carrier. It is more preferred that it is present in at least 1% and preferably from about 1% to about 94% by weight of the pharmaceutical composition. It is more preferred that the inorganic salt is present in amounts ranging from about 3% to about 60% by weight of the pharmaceutical composition and even more preferably from about 5 to about 40% by weight of the pharmaceutical composition and most preferably from about 10% to about 20% by weight of the pharmaceutical composition.
Without wishing to be bound, it is believed that the inorganic salt interacts with the water insoluble polymer to form a water insoluble barrier by coating the medicament partially or completely, thereby retarding the release of the drug. To be effective, however, the drug must be present in a certain minimal level. In the present invention, the drug is present in amounts greater than at least 5% by weight. Therefore, the inorganic salt and the water insoluble polymer are present in effective amounts relative to the concentration of drug (at least 5%), i.e., both the water insoluble polymer and the inorganic salt are present in amounts effective to retard the release of the drug especially in aqueous media, e.g., in the gastrointestinal tract. As indicated hereinabove, they are present in amounts effective to form a partial or complete barrier or coating around the drug to retard the release of the drug. It is preferred that the inorganic salt is present in amounts by weight equal to or greater than the insoluble polymer. In a more preferred embodiment, it is preferred that the weight ratio of inorganic salt to polymer is at least about 1:1 and more preferably is greater than about 2.5 to 1. In an embodiment, the weight ratio is greater than about 6:1 and more preferably greater than about 9:1. It is more preferred that the weight ratio ranges from about 1:1 to about 100:1 and more preferably from about 1:1 to about 20:1 and most preferably from about 1:1 to about 15:1.
It is also preferred that the weight ratio of drug to inorganic salt is greater than about 0.5 and more preferably greater than about 0.25. It is preferred that the weight ratio ranges from about 0.1 to about 10 and more preferably from about 0.25 to about 10. Furthermore, it is also preferred that the weight ratio of drug to water insoluble polymer is in the weight ratios given hereinabove. Moreover, in the more preferred embodiments, the weight ratios of drug to water insoluble polymer and the drug to water insoluble inorganic salt are both within the ranges indicated. In the most preferred embodiment, these two ratios are within the ranges indicated and also the weight ratio of water insoluble inorganic salt to water insoluble polymer is within the range indicated hereinabove.
The active ingredient can be of any type of medication which acts locally in the mouth or acts systemically, which in the case of the latter, can be administered orally, to transmit the active medicament into the gastrointestinal tract and into the blood, fluids and tissues of the body.
Representative active medicaments include antacids, anti-inflammatory substances, coronary vasodilators, cerebral vasodilators, peripheral vasodilators, anti-infectives, psychotropics, antimanics, stimulants, anti-histamines, laxatives, decongestants, vitamins, gastro-intestinal sedatives, antidarrheal preparations, anti-anginal drugs, vasodilators, antiarrythmics, anti-hypertensive drugs, vasoconstrictors drugs used for migraine treatments, anticoagulants and antithrombotic drugs, analgesics, anti-pyretics, hypnotics, sedatives, anti-emetics, anti-nauseants, anticonvulsants, neuromuscular drugs, hyper- and hypoglycemic agents, thyroid and antithyroid preparations, diuretics, antipasmodics, uterine relaxants, mineral and nutritional additives, antiobesity drugs, anabolic drugs, erythropoietic drugs, antiasthmatics, expectorants, cough suppressants, mucolytics, antiuricemic drugs and other drugs or substances acting locally in the mouth, such as topical anagetics, local anaesthetics, etc.
Typical active ingredients include gastro-intestinal sedatives such as metoclopramide and propantheline bromide; antacids such as aluminium trisilicate, aluminium hydroxide and cimetidine; anti-inflammatory drugs such as phenylbutazone, indomethacin, naproxen, ibuprofen, flurbiprofen, diclofenac, dexamethasone, predinisone and prednisolone; coronary vasodilator drugs such as glyceryl trinitrate, isosorbide dinitrate and pentaerythritil tetranitrate; peripheral and cerebral vasodilators such as soloctidilum, vincamine, naftidorofuryl oxalate, co-dergocrine mesylate, cyclandelate, papaverine and nicotinic acid; anti-infective substances such as erythromycin stearate, cephalexin, nalidixic acid, tetracycline hydrochloride, ampicillin, flucloxacillin sodium, hexamine mandelate and hexamine hippurate; neuroleptic drugs such as flurazepam, diazepam, temazepam, amitryptyline, doxepin, lithium carbonate, lithium sulfate, chlorpromazine, thioridazine, trifluperazine, fluphenazine, piperothiazine, haloperidol, maprotilline hydrochloride, imipramine and desmethylimipramine; central nervous stimulants such as methylphenidate, ephedrine, epinephrine, isoproterenol, amphetamine sulfate and amphetamine hydrochloride; antihistamic drugs such as diphenhydramine, diphenylpyraline, chlorpheniramine and brompheniramine; anti-diarrheal drugs such as bisacodyl and magnesium hydroxide; the laxative drug, dioctyl sodium sulfoxuccinate; nutritional supplements such as ascorbic acid, alpha tocopherol, thiamine and pyridoxine; anti-spasmodic drugs such as dicyclomine and diphenoxylate; drugs affecting the rhythm of the heart, such as verapamil, nifedipine, diltiazem, procainamide, disopyramide, bretylium toxylate, quinidine sulfate and quinidine gluconate; drugs used in the treatment of hypertension such as propranolol hydrochloride, guanethidine mono-sulphate, methyldopa, oxprenolol hydrochloride, captopril and hydralazine; drugs used in the treatment of migraine such as ergotamine; drugs affecting coagulability of blood suchas epsilon aminocaproic acid and protamine sulfate; anagesic drugs such as acetylsalicyclic acid, acetaminophen, codeine phosphate, codeine sulfate, oxydodone, dihydrocodeine tartrate, oxycodeinone, morphine, heroin, nalbuphine, butorphanol tartrate, pentazocine hydrochloride, cyclazacine, pethidine, buprenorphine, scopolamine and mefanamic acid; anti-epileptic drugs such as phenytoin sodium and sodium valproate; neuromuscular drugs such as dantrolene sodium; substances used in the treatment of diabetes such as tolbutamide, disbenase glucagon and insulin; drugs used in the treatment of thyroid gland dysfunction such as triodothyronine, thyroxine and propylthiouracil; diuretic drugs such as furosemide, chlorthalidone, hydrochlorthiazide, spironolactone and trimterene; the uterine relaxant drug ritodrine; appetite suppressants such as fenfluramine hydrochloride, phentermine and diethylproprion hydrochloride; anti-asthmatic and bronchodilator drugs such as aminophyline, theophyline, salbutamol, orciprenaline sulphate and terbutaline sulphate; expectorant drugs such as fuaiphenesin; cough suppressants such as dextromethorphan and noscapine; mucolytic drugs such as carbocisteine; anti-septics such as cetylpyridinium chloride, tyrothricin and chlorhexidine; decongestant drugs such as phenylpropanolamine and pseudoephedrine; hypnotic drugs such as dichloralphenazone and nitrazepam; anti-nauseant drugs such as promethazine theoclate; haemopoietic drugs such as ferrous sulphate, folic acid and calcium gluconate; uricosuric drugs such as sulphinpyrazone, allopurinol and probenecid.
Vitamins include such vitamins as vitamin A, vitamin D, vitamin B (d-xcex1-tocopherol acetate, etc.), vitamin B1 (dibenzoylthiamine, fursultiamine hydrochloride, etc.), vitamin B1 (dibenzoylthiamin, fursultiamine hydrochloride, etc.), vitamin B2 (riboflavin butyrate, etc.), vitamin B6 (pyridoxine hydrochloride, etc.), vitamin C (ascorbic acid, sodium L-ascorbate, etc.), vitamin B12 (hydroxocobalamin acetate, etc.); minerals such as calcium, megnesium, and iron.
In addition, the drug may be a pharmaceutically acceptable salt of any of the active ingredients enumerated hereinabove.
A lubricant may additionally be and is preferably present in the pharmaceutical formulations of the present invention especially when in the form of a tablet. xe2x80x9cLubricantxe2x80x9d, as used herein, refers to a material which can reduce the friction between the die walls and the punch faces which occurs during the compression and ejection of a tablet. The lubricant prevents sticking of the tablet material to the punch faces and the die walls. As used herein, the term xe2x80x9clubricantxe2x80x9d includes anti-adherents.
Tablet sticking during formation and/or ejection may pose serious production problems such as reduced efficiency, irregularly formed tablets and non-uniform distribution of the medicament in the formulation. To avoid this problem, the present invention contemplates utilizing a lubricating effective amount of the lubricant. Preferably, the lubricant is present in amounts ranging from about 0.1% to about 5% by weight and more preferably from about .5% to about 2% by weight of the pharmaceutical composition, e.g., tablet. Examples of lubricants include stearate salts, e.g., alkaline earth and transition metal salts, such as calcium, magnesium and zinc stearates; stearic acid; polyethylene oxide; talc; hydrogenated vegetable oil; and vegetable oil derivatives, and the like. In addition, the pharmaceutical composition, e.g., tablet, may contain a combination of more than one type of lubricant. Other lubricants that also can be used include silica, silicones, high molecular weight polyalkylene glycol, e.g., high molecular weight polyethylene glycol, monoesters of propylene glycol, and saturated fatty acids containing about 8-22 carbon atoms and preferably 16-20 carbon atoms. The preferred lubricants are the stearate salts, especially magnesium and calcium stearate and stearic acid.
Excipients, such as plasticizers, for example, diethylphthalate (DEP), dibutyl sebacate, triethyl citrate, triacetin, vegetable and mineral oils, polyethylene glycol, and the like, may optionally be present. They enhance tableting characteristics and modify the release of the drug in the gastrointestinal tract when administered to the mammal, and they are present in amounts effective to modify the release in the gastrointestinal tract. The present inventor has noted that, in some cases, the combination of the water-insoluble salt and the water insoluble polymer caused the rate of release of the drug to be slower than desired. In such cases, an excipient, e.g., plasticizer, filler or the like is added to increase the rate of release of the drug. Thus, in one embodiment, a plasticizer may be present in amounts effective to increase the rate of release. Preferably, the plasticizer, when present, is present in the pharmaceutical formulations of the present invention in amounts ranging from about 0.01% to about 25%, and more preferably from about 0.1% to about 10% and most preferably from about 1% to about 5% by weight of the carrier.
Fillers, such as maltodextrin, sugar, lactose, and microcrystalline cellulose may also be present. They are preferably present in amounts ranging from about 2% to about 70% by weight of the carrier, and more preferably from about 10% to about 50% of the carrier and most preferably from about 20% to about 40% by weight of the carrier.
One of ordinary skill in the art understands that excipients, e.g., fillers or plasticizers, have several functions in the pharmaceutical composition. For example, they may be added to enhance tableting characteristics or increase the bulk of the pharmaceutical composition. It is within the purview of one of ordinary skill in the art to determine how much excipient is to be added and the objective that he wishes to accomplishing by adding the same. The amounts given hereinabove for the plasticizer and the fillers are to be understood as preferred embodiment.
Other optional ingredients that are also typically used in pharmaceuticals may also be present, such as coloring agents, preservatives (e.g., methyl parabens), artificial sweeteners, flavorants, anti-oxidants, and the like. Artificial sweeteners include, but are not limited to, saccharin sodium, aspartame, dipotassium glycyrrhizinate, stevia, thaumatin and the like. Flavorants include, but are not limited to, lemon, lime, orange and menthol. The colorants include, but are not limited to, various food colors, e.g., FDandC colors, such as FDandC Yellow No. 6, FDandC Red No. 2, FDandC Blue No. 2, food lakes and the like. Examples of anti-oxidants include ascorbic acid, sodium metabisulphite and the like. These optional ingredients, if present, preferably are present in amounts ranging from about 0.1% to about 5% by weight of the tablet and most preferably less than about 3% (w/w) of the tablet.
The formulations of the present invention are preferably uncoated, but may be coated if desired with one of the many readily available coating systems. However, the combination of the water insoluble polymer and the salt is present in the carrier, and the combination is not present in the coating.
Coating the pharmaceutical composition of the present invention in a unit dosage form, e.g., tablets, serves to mask the taste of the pharmaceutical composition of the present invention. It also makes the unit dosage form of the pharmaceutical composition of the present invention, e.g., tablet, easier to swallow and, in some cases, improves the appearance of the dosage form. The pharmaceutical compositions, e.g., tablet, can be sugar coated and are coated according to the procedures well known in the art. Alternatively, the unit dosage forms of the pharmaceutical composition of the present invention, e.g., tablets, can be coated with any one of numerous polymeric film coating agents frequently employed by formulation chemists. Representative examples of such film coating agents include hydroxypropyl methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, methyl cellulose, ethyl cellulose, acrylic resins, providone, polyvinyl diethylaminoacetate, cellulose acetate phthalate, polyvinyl acetate phthalate, acrylic latex emulsions, ethyl cellulose latex emulsions, and the like. If the coating material is present, it is present in less than about 5% by weight of the tablet, and more preferably about 2-3% w/w.
A procedure for preparing the formulation of the present invention is by the wet granulation process in which all of the components, i.e., medicament, inorganic salt, polymer, and any additional excipient and other optional ingredient(s), except the lubricant, are mixed with a sufficient amount of a granulating solvent to form a substantially uniform blend in a suitable blender, such as a planetary mixer. The granulating vehicle is one that is inert to the components and has a low boiling point, i.e., preferably less than about 120xc2x0 C. It is preferably a solvent such as an alcohol containing 1-4 carbon atoms, e.g., isopropyl alcohol or ethanol or water or acetone and the like. An aqueous dispersion can also be utilized, especially if the polymeric sustained release material is a methyl methacrylate copolymer, as described above. In a preferred embodiment, the type of granulating vehicle used is dependent upon the identity of the sustained release polymer. It is preferred that when the sustained release material is a copolymer of methyl methacrylate or ethyl acrylate, the granulating vehicle is an alcohol such as isopropyl alcohol or an aqueous latex dispersion of said copolymer.
The substantially uniformly blended mixture may next optionally be milled, e.g., passed through a screen, sieve, etc. to reduce the size of the particles thereof. The screen or sieve, and the like is preferably less than about 140 mesh, and more preferably less than about 100 mesh, and even more preferably, less than about 40 mesh, and most preferably less than about 25 mesh.
Next, the blend is dried. In this step, the solvent is removed from the blend by physical means known to the skilled artisan, e.g., by evaporation or filtration. The resulting granules are again milled, e.g., passed through a screen or sieve to further reduce the size of the particles to the desired size. Then the lubricant is added, and the granules are mixed to provide a uniform and homogenous blend, and then the resulting mixture is compressed to form a tablet. In a preferred variation, the blend can be simultaneously granulated in the granulation vehicle and dried, such as by using a fluid bed granulation process.
When the mixture is homogeneous with respect to the drug, a unit dosage form of the mixture is prepared. The following procedure describes the preparation of a tablet, but once the mixture is homogenous, it can be used to prepare any suitable dosage form used in the pharmaceutical arts by conventional methods. The methodology for preparing a tablet containing the pharmaceutical composition of the present invention is exemplary and it is to be understood that the present invention should not be so limited.
In preparing a tablet, the homogenous mixture is compressed into a tablet form using a tablet machine typically utilized in the pharmaceutical arts. More specifically, the mixture is fed to the die of a tablet press and sufficient pressure is applied to form a solid tablet. Such pressure can vary, and typically ranges from about 1,000 psi to about 6,000 psi and preferably about 2,000 psi force.
After the tablet is formed, the tablet is coated with materials normally used in pharmaceuticals, if desired. If coated, the coating is prepared by techniques known in the art.
As a result of the process described herein, a tablet product is obtained which has the desired hardness and friability typically found for pharmaceutical tablets. The hardness is preferably 5-25 Kp and more preferably 8-20 Kp. In addition, the tablet has an excellent drug release profile. More specifically, it has a predetermined controlled and sustained action and a regular delayed pattern so that the drug is available over a period of up to 36 hours or longer, depending upon the precise tablet size, the identity of the active ingredient, hardness and the particular carrier composition and the needs of the patient. Furthermore, the release profile of each formulation is substantially uniform. Finally, the tablets prepared in accordance with the present invention are hard and dense, have low friability and provide controlled and sustained release over an extended period.
Besides a tablet, the uniformly blended mixture of active ingredient, water insoluble polymer, water insoluble inorganic salt, and any other additional components, can be made into a pellet, capsule, granule, pill or a dragee using conventional techniques known in the art.
The term unit dosage form as employed herein refers to physically discrete units suitable as unitary dosages to human subjects and other mammals, each unit containing a predetermined quantity of medicament calculated to produce the desired effect, in association with the other ingredients of the formulation disclosed herein.
In the formulations described hereinabove, the percent of the components are calculated on a dry weight basis, without reference to any water or other components present.
Unless indicated to the contrary, all percentages are weight percentages relative to the tablet.
Moreover, the terms xe2x80x9cdrugxe2x80x9d and xe2x80x9cmedicamentxe2x80x9d are used interchangeable. Furthermore, the terms xe2x80x9csustained releasexe2x80x9d and xe2x80x9ccontrolled releasexe2x80x9d are being used interchangeably.
As used herein, the singular shall refer to the plural and vice versa.

Controlled release oral dosage for suitable for oral administration


A tamper resistant mixture adjustment screw arrangement for a carburetor. The arrangement includes a carburetor body having at least one air/fuel adjustment screw threaded therein. The adjustment screw has a threaded shank and a head portion. The head portion is defined by a smooth top surface and an undulant, uneven side surface capable of being engaged and mated by an adjusting tool having a complementary undulant, uneven side surface capable of being engaged and mated by an adjusting tool having a complementary undulant, uneven surface for initially adjusting the air/fuel mixture in the carburetor. A blocking curb extends from the carburetor body to a level which at least substantially corresponds to a projecting extent of each adjustment screw and being closely spaced to the screw head to prevent the screw from being turned by commonly available tools, but to permit the screw to be adjusted by the adjusting tool.

This invention relates to carburetors and, more particularly, to a tamper resistant mixture adjustment screw arrangement for a carburetor.
Environmental protection statutes and regulations are beginning to place limits on the combustion products of small power tools, such as gasoline powered lawn mowers, edgers, chain saws, and line trimmers. Such powered tools usually employ a diaphragm carburetor to control the air/fuel mixture fed to the two-cycle gasoline engine. Fuel is fed to an engine intake path by a fuel pump. The fuel pressure is regulated at a fixed pressure by a fuel pressure regulator. The fuel pressure regulator is equipped with a fuel chamber that stores fuel sent from the fuel pump. A diaphragm that forms one of the fuel chamber walls and a control valve that is interlocked to the motion of the diaphragm opens and closes the fuel chamber inlet. Thus, in any position, fuel is properly supplied to the engine. Fuel travels to the intake path from the fuel chamber through either a main fuel path or an idle fuel path.
A manual fuel mixture adjustment screw is provided for independently controlling the effective areas of the main and idle fuel paths. The adjustment screw includes a needle-shaped valve that can be advanced into or withdrawn from the fuel path.
The carburetor mixture adjustment screws are semi-fixed positionally to limit the amount of adjustment the operator can achieve for exhaust emissions requirements. The carburetor mixture needles can still be adjusted but the angular range is limited, usually by a cap or similar design preventing full rotational movement. Such an arrangement is disclosed and described in U.S. Pat. No. 5,603,869.
During the manufacturing of the end product the carburetor is adjusted to achieve peek performance and obtain acceptable exhaust emissions output. The 2-cycle engine is tested and the carburetor mixture needles are adjusted by the manufacturer to obtain a specific performance specification during the assembly process. After these performance objectives are achieved, the adjustor installs the limiter caps onto the mixture needles. Frequently, during the installation process of the limiter caps, the carburetor adjustment changes. When this occurs the final set point of the carburetor can either be unacceptable for performance or for exhaust emission standards.
Carburetor mixture needles on 2-cycle hand held products are very sensitive because the needle tip and jet diameters are very small. This is because the engine displacement size is small compared to those of larger engines used on automobiles, motorcycles, and the like. With the small engine displacement the fuel requirements is proportionally smaller which is what determines the effective jet size.
Depending on the 2-cycle engine design and the end product application, the carburetor can be equipped with either 2 mixture needles or a single mixture needle. With the two-mixture needle design both a low speed (idle) and a high speed (wide open throttle) fuel richness can be adjusted. On a single mixture needle design, only the high-speed mixture can be adjusted. This is acceptable on products that do not require strict performance at a low speed and can tolerate a fixed fuel flow rate.
The problem of carburetor adjustment changing when the limiter caps are installed are caused by several environmental factors. One factor is the amount of physical pressure required to install the cap onto the mixture needle. Several limiter cap designs rely on an interference fit between the mixture needle and the limiter cap to retain the cap on the needle. The force required to press the cap on the needle often moves the needle, and can even bend the needle.
Another factor that can affect the mixture needle is side pressure which tends to load the needle off center. The side load is created by the limiter cap design. Several carburetor designs rely on two mixture needles with close proximity to each other. On the two needle carburetor designs, the limiter caps have physical stops that are designed to contact the other mixture needle cap. This close proximity and tight design clearances of the two limiter caps can create a side load that will physically move the needles off their natural center to change the flow rate through the jet.
Further, another factor is the surrounding construction. Products like chain saws have housings and grommets designed with close proximity to the carburetor mixture needles. Grommets are used to keep dirt and debris out of the carburetor housing, which can cause damage to the product. These grommets can also apply a side load to the needles causing them to skew from their natural center.
Still further, another factor that can affect the mixture needle is vibration caused by the 2-cycle engine. This vibration creates a resonate vibration on the needle and will change the flow characteristics of the needle tip and jet nozzle. The length of the needle and additional mass of the limiter caps increases the vibration affect to the flow.
Another problem with the limiter cap application on carburetor mixture needles is the span of adjustment available. Government regulations has mandated that the limits of adjustment must be inspected and fall within the required emissions limits. The consistent reduction in allowable exhaust emissions has forced manufacturers to decrease the amount of allowable consumer adjustment to a point where any adjustment is impractical and provides no real benefit to the consumer.
These tight government regulations have also caused problems with the manufacturing of these products and the adjustment parameters are so stringent that the carburetor adjustment has become critical to the assembly operation. The strict adjustment specification sometimes requires several installations of limiter caps on one product before an acceptable set point is achieved, and the product is allowed to be shipped. This assembly bottleneck is a major cost factor in end product in terms of labor hours to build the final product.
A need exists for an arrangement which permits the carburetor mixture needles to be adjusted by the manufacturer or an authorized dealer to position the needle valve or valves at a position to obtain a specific performance specification during the assembly process or during reconditioning by the dealer, but prevents adjustment by the consumer.
According to the invention, the carburetor mixture needles are designed so that the limiter cap can be omitted from the final design. This is achieved by a carburetor mixture needle design that cannot be turned by common hand tools, and is tamper resistant. The carburetor mixture adjustment performed by the manufacturer is considered fixed and non-adjustable by the consumer. This is not seen to be a problem since the strict emissions regulations has forced the manufacturers into carburetor designs that did not allow for any reasonable adjustment and therefore the consumer has no ability to correct the mixture setting.
The new tamper resistant mixture needle design according to this invention has a needle valve head that can be turned only with a special tool accessible by the manufacturer and authorized service dealers to perform carburetor adjustments. The mixture needle heads preferably have a special straight knurl pattern on the outside diameter of the head of the mixture needle that allows a special screwdriver tool to engage and turn the mixture needles for factory adjustment. The straight knurl design can be formed in different shapes and achieve the same affect. Another style would be splined or gear-like teeth.
There is no common tool commercially available for this style fastener or hardware. The tool according to this invention has an end formed with a mating profile that engages the straight knurl shape on the mixture needle heads. The teeth-like protrusions on the tool are staggered to ensure easy alignment. The number of teeth in the tool may be varied as long as they correspond with the mixture needle knurl spacing.
The advantage of the tamper resistant needle design is the stability of the adjustment achieved with this style mixture needle. The problems seen with the prior art design with respect to side loading, vibration, and changes after the limiter caps were installed are all minimized. This is mainly because no external forces are acting upon the mixture needles, and the needles do not have additional mass attached to the end of them.
Another advantage of this style needle design is in the form of assembly labor. The time to adjust the carburetor properly is reduced because of the mixture stability, and the setting does not require re-adjustment because the limiter cap installation may have changed the performance outside the acceptable parameters. The time to install the limiter caps on the mixture needles is also eliminated from the assembly operation.
There are also advantages from the emission regulations standpoint. Government emissions requirements are audited and monitored by the manufacturer for compliance. The time spent testing and auditing product is reduced because the non-adjustable style mixture needles. There is only one position (asset) and no limits, such as on limiter cap style, which still have some range of movement allowed.
In order to achieve the tamper resistant requirement as outlined by the two government agencies, California Air Resources Board (CARB), and Environmental Protection Agency (EPA), described above, the manufacturer has to prove that the design is tamper resistant. The needle head design is not enough if the consumer can still access and turn the mixture needles with, for example, pliers. So to prohibit use of other means of adjustment, the surrounding construction is designed to limit access to the mixture needles.
On gas chain saws a carburetor grommet can be used to prevent access to the mixture needles. The grommet has a small access hole that allows the adjustment tool to reach the needles for adjustment but is sized to prevent needle adjustment by other means. The grommet is designed so it cannot be removed from the chain saw without major disassembly of the product by means of a protruding wall that prevent removal from the mixture needles.
On string trimmers, leaf blowers, hedge trimmers and the like, the carburetor location may be more accessible than that on a chain saw, so the carburetor casting is provided with an additional protrusion that shields the mixture needles from being assessed and turned. This protrusion may be integral to the carburetor body casting, and therefore cannot be removed without permanent damage to the carburetor. Other means of construction are possible to achieve the same function as the integral wall. For example, a separate stamped steel cup formed in the same shape as the wall can be attached to the carburetor body.
According to one aspect of this invention, a blocking curb extends from the carburetor body to a level which at least substantially corresponds to a projecting extent of each adjustment screw. The blocking curb is closely spaced to the head of the adjusting screw to prevent the screw from being turned by commonly available tools, but to permit the screw to be adjusted by a special adjusting tool.
According to one aspect of the invention the blocking curb comprises a series of posts molded into the carburetor body. According to another aspect of the invention the blocking curb is integral with the carburetor body, surrounds the adjustment screw or screws, and has an inside arcuate surface which is closely spaced to each head for at least a major portion of the side surface of each head. According to a further aspect of the invention, the blocking curb comprises a drawn sleeve which surrounds the adjustment screw or screws and is captured by the adjustment screw spring.
According to a still further aspect of this invention, the blocking curb is a grommet which extends from the carburetor body and forms a chamber surrounding each adjusting screw head. A cylindrical access opening is provided for each screw head and each access opening is axially aligned with a screw head. The diameter of each opening is slightly larger than the diameter of each axially aligned screw head to prevent the screw from being turned by commonly available tools, but to permit the screw to be adjusted by a special adjusting tool adapted to engage a sidewall of the screw head.

Tamper resistant carburetor mixture needles