Penicillins are known to degrade in liquid formulations. This work, therefore, attempts to find a means of maintaining stability of pencillins in liquid formulations. Cloxacillin sodium and benzathine benzylpenicllin powdered injection were reconstituted in three different injectable fluids: 0.9% sodium chloride, 5% dextrose and water for injection. These drug solutions were frozen using domestic refrigerator (0-4oC) and defrozen using microwave oven and room temperature thawing for 360 hours. The third and fourth samples, which were not frozen at all, were allowed to remain in the refrigerator for 360 hours respectively. These served as controls. The decomposition rate constants for cloxacillin sodium in 5% dextrose were 4.8 x 10-4, 1.88 x 10-3 and 3.68 x 10-3 mg ml-1 h-1 for microwave thawing (MWT), room temperature defreezing (RTD) and non–frozen (NF) respectively, while in 0.9% sodium chloride, the decomposition rate constants were 1.13 x 10-3, 2.05 x 10-3 and 3.85 x 10-3 mg ml-1 h-1 for MWT, RTD and NF respectively and in water for injection, 8.4x 10-4, 1.56x 10-3 and 2.67 x 10-3 mg ml-1 h-1 for MWT, RTD and NF respectively, after reconstitution. The potency loss was minimal after thawing with microwave oven. The decomposition rate constants for benzathine benzylpenicillin were as follows: in 5% dextrose-1.80 x 10-3, 1.03 x 10-3 and 1.29 x 10-4mg ml-1 h-1 for MWT, RTD and NF; in 0.9% sodium chloride-5.31 x 10-3, 4.39 x 10-3 and 1.01 x 10-3 mg ml-1 h-1 for MWT, RTD and NF; and in water for injection-3.60 x 10-4, 1 .11x 10-3 and 1.54 x 10-3 mg ml-1 h-1 for MWT, RTD and NF respectively. Benzathine benzylpenicillin was found to be more stable in water for injection after reconstitution and potency loss was minimal during microwave thawing than during room temperature defreezing.
KEYWORDS: Penicillins, freezing, microwave thawing, potency loss.