INVITRO DEGRADATION AND SOLUTE RELEASE FROM ERODIBLE POLYANHYDRIDE SUPPORTS CONTAINING SKELETAL BETA-ALANINE RESIDUES

More efficient means of administering drugs at controlled rates are continuously being sought. An important alternative is biodegradable polymers which do not have to be removed once implanted. A class of biodegradable polymers studied by several groups is the polyanhydrides. The synthesis of a novel class of polyanhydrides containing skeletal amino acid residues was recently described (Staubli et al., 1990). In the present study, the degradation kinetics and the potential applications in controlled drug release of one of these polymers, poly(N-trimellitylimido-beta-alanine-co-sebacic anhydride) (PTIASA; 20:80), were investigated simultaneously for the first time. Drug-polymer discs were prepared by compression molding using either acid orange or sodium salicylate as the model drug (approximately 30% weight loading). In vitro incubation experiments were carried out in buffer solutions of pH 7.4 and 10.0 at 37-degrees-C. The appearance of beta-alanine (a polymer by-product) and drug in solution was followed spectrophotometrically for up to 240 h. Mass balances were then performed to determine the rates of polymer degradation and drug release. Drug-free PTIASA discs decreased in thickness throughout the incubation period at both pH's but maintained their shape. The degradation rates (in terms of the appearance of beta-alanine in solution) were relatively constant (zero-order kinetics) and higher at pH 10.0. The drug-free discs degraded completely in 7-8 days at pH 10.0 and in about 10 days at pH 7.4. On the other hand, the drug-loaded PTIASA discs swelled initially and disintegrated partially later on. In the acid orange-PTIASA experiments about 90% of the drug was released in the first 15 h of incubation, the remaining 10% being released at a relatively constant and slower rate thereafter. When sodium salicylate was used as the test drug, the magnitude of the initial burst in drug release was reduced and the useful life of the formulations extended. This study clearly shows the potential use of these novel amino acid-containing polyanhydrides in controlled release formulations.