EFFECT OF POLYMER CRYSTALLINITY ON PAPAVERINE RELEASE FROM POLY (L-LACTIC ACID) MATRIX

The release of papaverine from poly (L-lactic acid) (P(L)LA) matrix wa s investigated. A cylindrical matrix (rod; 1 mm diameter, 10 mm length ) was prepared by the heat compression method from P(L)LA and papaveri ne. In the rod thus obtained, papaverine was dissolved in the P(L)LA m atrix. It was revealed that papaverine release from the rods is contro lled by drug diffusion, and not by polymer erasion. Furthermore, it wa s found that the release profile consisted of two sequential stages, s uggesting that the environment for the diffusion changes during the co urse of release. X-ray diffraction, DSC measurements and gel permeatio n chromatography showed that initially the P(L)LA matrix was amorphous , but it became semicrystalline during the release study. The crystall ization occurred at almost the same time as the transition from the fi rst to the second release stage. In addition, a rod that had been prec rystallized in humid air prior to the release study showed one monoton ous release profile. These findings reveal that the transformation of P(L)LA matrix from amorphous to semicrystalline induces the transition from the first to the second release stage. The drug release rate was faster in the second stage than in the first stage. Scanning electron microscopy showed that the amorphous P(L)LA matrix at the first stage has a homogeneous structure. In contrast, the crystallized matrix at the second stage has a microporous structure. Therefore, it was conclu ded that in the second stage a drug can diffuse through water in the m icropores of the crystallized matrix faster than through the homogeneo us amorphous polymer matrix in the first stage. (C) 1997 Elsevier Scie nce B.V.