stoichiometric ratio was determined by phase solubility method and complex was prepared using kneading , spray drying and lyophilization . the complexes were characterized by differential scanning calorimetry , fourier - transform infrared spectroscopy , scanning electron microscopy , and powder x - ray diffraction studies , drug content , wettability , dissolution and parameter for tabletting efficiency . phase solubility analysis has been among the preliminary requirements for optimizing the development of inclusion complexes of drugs as it permits the evaluation of the affinity between a cd and drug molecule in water . increased solubility may be due to improved dissolution of ntr particles in water due to the presence of cds . the solubility of ntr increased by 218-fold at 37c and 158-fold at 25c and121-fold at 37c and 72-fold at 25c at a 200 mm concentration of sbe--cd and hp -cd respectively . this curve indicated an increase in the solubility of ntr with an increase in the concentration of the cd in water . increasing the amount of the cd increased the amount of ntr entering the water , improving the aqueous solubility of ntr . gibbs free energy values were all negative , indicating the spontaneous nature nitrazepam solubilization and their value decreased with increase in the cyclodextrin concentration , demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrin increased . drug content of hpcd and sbecd formulations was found to be 85% and 96% , respectively . the results of dsc and ftir study showed that nitrazepam was compatible with both cyclodextrins and complex formed by spray drying and lyophilization is best . the results of wettability , dissolurion and in vitro release study were shown in figure 1 . solubility studies revealed a significant increase in the aqueous solubility of ntr with an increase in the concentration of hp--cd and sbe--cd . the maximum concentration of hp-  -cd and sbe--cd studied ( 200 mm at 37c ) resulted in 121-fold and 218-fold improvement in the saturation solubility of nitrazepam . an inclusion complex of nitrazepam with hp--cd and sbe--cd at a molar ratio of 2:1 was successfully prepared by kneading , spray - drying , and lyophilization . the greatest improvement in solubility and in vitro drug release was observed with an inclusion complex prepared with sbe--cd by lyophilization . the solubility and in vitro drug release of a physical mixture improved to a lesser degree than did that of complexes prepared by kneading , spray - drying , and lyophilization . these finding are extremely important from commercial point of view as the prepared complex remedies the drawback of ntr 's poor dissolution profile .
the objectives of this research were to prepare and characterize inclusion complexes of nitrazepam with hydroxypropyl--cyclodextrin ( hpcd ) and sulfobutyl ether -cyclodextrin ( sbecd ) to study the effect of complexation on the dissolution rate of nitrazepam , a water - insoluble drug . 
 the phase solubility profile of nitrazepam with hydroxypropyl- -cyclodextrin and sulfobutyl ether -cyclodextrin was an ap - type , indicating the formation of 2:1 stoichiometric inclusion complexes . 
 gibbs free energy values were all negative , indicating the spontaneous nature nitrazepam solubilization and their value decreased with increase in the cyclodextrin concentration , demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrins increased . 
 complexes of nitrazepam were prepared with cyclodextrin using various methods such as physical mixing , kneading , spray - drying and lyophilization . 
 the complexes were characterized by differential scanning calorimetry , fourier - transform infrared , scanning electron microscopy and powder x - ray diffraction studies . 
 these studies indicated that a complex prepared by lyophilization had successful inclusion of the nitrazepam molecule into the cyclodextrin cavity . 
 complexation resulted in a marked improvement in the solubility and wettability of nitrazepam . among all the samples , a complex prepared with sulfobutyl ether -cyclodextrin by lyophilization had the greatest improvement in the in vitro rate of nitrazepam dissolution . 
 the mean dissolution time for nitrazepam decreased significantly after preparing complexes . 
 the similarity factor indicated a significant difference between the release profiles of nitrazepam from complexes , physical mixtures and plain nitrazepam . to conclude that , the tablets containing complexes prepared with cyclodextrins had significant improvement in the release profile of nitrazepam as compared to tablets containing nitrazepam without cyclodextrin .