DEVELOPMENT OF A TRANS-MUCOSAL CONTROLLED-RELEASE DEVICE FOR SYSTEMICDELIVERY OF ANTIANGINAL DRUGS PHARMACOKINETICS AND PHARMACODYNAMICS

Oral mucosa is well-known to be one of the best routes for drug absorp tion. But very few R and D works have been initiated to investigate th e feasibility of using this site to control drug delivery. A transmuco sal controlled-release device, which is capable of achieving excellent absorption and controlled release of drugs, has been developed. The d evice is a tablet-shaped mucoadhesive system which is composed of two layers. The upper layer is a fast-release layer and the lower layer is a sustained-release layer, and designed to be applied between buccal and gingival mucosae. Both layers are formulated from synthetic polyme rs to control the release of drugs. Isosorbide dinitrate(ISDN), a well -documented antianginal drug, is known to be susceptible to extensive presystemic elimination when taken orally. It was used as the candidat e drug and the systemic bioavailability was studied in human and obser ved to be improved by as much as 5 fold when compared to a marketed or al sustained-release tablet; On the other hand, much smaller amount of metabolites was formed. The plasma profile of ISDN has also been obse rved to be substantially prolonged (12 hrs as compared to less than 1 hr for sublingual tablet and spray product on the market). These obser vations have demonstrated that this device is capable of not only bypa ssing hepatic ''first-pass'' metabolism but also having a sustained-re lease property of prolonging the release of ISDN. Clinical studies per formed in the anginal patients for up to one year have demonstrated th e therapeutic benefits of this device in achieving a substantial reduc tion in the frequency of anginal attacks.