SUSTAINED-RELEASE BUCCAL DOSAGE FORMS FOR NITROGLYCERIN AND ISOSORBIDE DINITRATE - INCREASED BIOAVAILABILITY AND EXTENDED TIME OF ABSORPTION WHEN ADMINISTERED TO DOGS

In order to achieve high bioavailability (BA) and an extended absorpti on time for nitroglycerin (GTN) and isosorbide dinitrate (ISDN), two d ifferent types of sustained-release buccal dosage forms were prepared: a slowly disintegrating plain tablet (plain SR-tab; disintegration ti me, 3-6 h) and a film-covered tablet in which disintegration was contr olled by a hole in the film coating, positioned on the top surface of the tablet (area of the hole, around 80% of the top surface) (covered SR-tab; disintegration time, 10-12 h). The BAs of GTN and ISDN after o ral administration of plain SR-tabs to dogs were 2% and 5%, respective ly. In contrast, the BAs of GTN and ISDN after gingival administration of the buccal dosage forms were almost complete (GTN plain SR-tabs, 1 78%; GTN covered SR-tabs, 102%; ISDN plain SR-tabs, 120%; ISDN covered SR-tabs, 89%). The high BAs obtained were attributed to the avoidance of presystemic elimination due to the use of the buccal route of admi nistration The duration of buccal absorption was largely dependent on the tablet disintegration time. plain SR-tabs did not prolong disinteg ration time appreciably, and therefore resulted in a relatively short absorption time (mean buccal absorption time, around 3 h with GTN plai n SR-tabs and around 7 h with ISDN plain SR tabs). On the other hand, covered SR-tabs resulted in constant absorption rates over 10 h. These findings indicate that gingival administration of slowly disintegrati ng buccal tablets is a useful method of increasing the BAs of these dr ugs. In particular, covered SR-tabs can afford constant rate absorptio n for at least 10 h. (C) 1997 Elsevier Science B.V.