期刊
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
卷 7, 期 3, 页码 333-343出版社
TAYLOR & FRANCIS LTD
DOI: 10.1081/PDT-120005730
关键词
amoxycillin; amphoteric drugs; drug degradation; poly(D,L-lactideco-glycolyde) (PLGA); polymer degradation-controlled release; RG503; surface erosion
Amoxycillin-poly (D,L-lactide-co-glycolide) (PLGA) compacts were prepared by direct compression of both powder mixtures or films in a pre-heated press. Release profiles generally showed two phases separated by an induction. period. Thus, both diffusion and polymer degradation mechanisms were involved in drug release, the relative importance of each depending on processing type and drug loading. Drug release parameters for each phase were determined. The fraction of total drug released, in the initial release phase, increased with drug loading and was much larger for compressed physical mixtures than for compressed composites prepared from coevaporate films. Comparison of the polymer mass loss profiles of drug-loaded and drug-free discs indicated that the presence of the amphoteric drug amoxycillin had little impact on the polymer degradation rate, in contrast to the marked acceleration previously reported for basic drugs. Significant drug degradation occurred and was associated with release at later times. Release data was fitted to all equation accounting for degradation of the drug on release and suggested accelerated amoxycillin degradation during the polymer degradation controlled release phase, consistent with changes in pH in the microenvironment of the eroding compact.
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