PURPOSE: The purpose of this study was to investigate both the in vitro and in vivo release of apomorphine from mucoadhesive powder formulations of Carbopol 971P and polycarbophil. METHODS: The in vitro drug release from the mucoadhesive formulations was studied using a modified USP XXII rotating basket. The pharmacokinetics of apomorphine given as a solution was determined after subcutaneous and intranasal administrations to rabbits. The animals also received intranasally the mucoadhesive dosage forms and immediate release lactose powder mixture. Comparisons were made between the salient pharmacokinetic parameters of the different dosage forms. RESULTS: Sustained in vitro drug release was obtained from the mucoadhesive formulations. Apomorphine was absorbed more rapidly in rabbits when administered intranasally than as a subcutaneous injection. The mucoadhesive formulations both gave sustained plasma drug concentrations and bioavailabilities comparable to subcutaneous injections. The times taken to achieve peak plasma drug concentrations from these mucoadhesive formulations were more than three-fold that of lactose. With these mucoadhesive formulations apomorphine lasted longer in the blood. It could be detected for up to 6-8 h compared to approximately 3 h for the other forms of administration. CONCLUSIONS: The nasal bioavailability of powders is higher than that of solutions. Drug release from the mucoadhesive powders was sustained and there was no significant difference between Carbopol 971P and polycarbophil.
PURPOSE: The purpose of this study was to investigate both the in vitro and in vivo release of apomorphine from mucoadhesive powder formulations of Carbopol 971P and polycarbophil. METHODS: The in vitro drug release from the mucoadhesive formulations was studied using a modified USP XXII rotating basket. The pharmacokinetics of apomorphine given as a solution was determined after subcutaneous and intranasal administrations to rabbits. The animals also received intranasally the mucoadhesive dosage forms and immediate release lactose powder mixture. Comparisons were made between the salient pharmacokinetic parameters of the different dosage forms. RESULTS: Sustained in vitro drug release was obtained from the mucoadhesive formulations. Apomorphine was absorbed more rapidly in rabbits when administered intranasally than as a subcutaneous injection. The mucoadhesive formulations both gave sustained plasma drug concentrations and bioavailabilities comparable to subcutaneous injections. The times taken to achieve peak plasma drug concentrations from these mucoadhesive formulations were more than three-fold that of lactose. With these mucoadhesive formulations apomorphine lasted longer in the blood. It could be detected for up to 6-8 h compared to approximately 3 h for the other forms of administration. CONCLUSIONS: The nasal bioavailability of powders is higher than that of solutions. Drug release from the mucoadhesive powders was sustained and there was no significant difference between Carbopol 971P and polycarbophil.