Bioavailability of apomorphine following intranasal administration of mucoadhesive drug delivery systems in rabbits

Purpose: The purpose of this study was to investigate both the in vitro and in vivo release of apomorphine from mucoadhesive powder formulations of Ca rbopol 971P and polycarbophil. Methods: The in vitro drug release from the mucoadhesive formulations was studied using a modified USP XXII rotating ba sket. The pharmacokinetics of apomorphine given as a solution was determine d after subcutaneous and intranasal administrations to rabbits. The animals also received intranasally the mucoadhesive dosage forms and immediate rel ease lactose powder mixture. Comparisons were made between the salient phar macokinetic parameters of the different dosage forms. Results: Sustained in vitro drug release was obtained from the mucoadhesive formulations. Apomor phine was absorbed more rapidly in rabbits when administered intranasally t han as a subcutaneous injection. The mucoadhesive formulations both gave su stained plasma drug concentrations and bioavailabilities comparable to subc utaneous injections. The times taken to achieve peak plasma drug concentrat ions 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 bioavaila bility of powders is higher than that of solutions. Drug release from the m ucoadhesive powders was sustained and there was no significant difference b etween Carbopol 971P and polycarbophil. (C) 1999 Published by Elsevier Scie nce B.V. All rights reserved.