MECHANISM OF DRUG-RELEASE FROM SILICONE MICROSPHERES CONTAINING POLYCARBOPHIL

The possibility of a pH-controlled drug release mechanism applying to silicone microspheres containing nicotinamide (NAM) and Polycarbophil (PCP), a pi-I-sensitive hydrogel, is evaluated. NAM-medicated PCP in t he 4:1 PCP-NAM wt ratio is dispersed, at the 20% or 40% concentration, in silicone in the form of osmotically active particles of around 15 mu m mean volume diameter, and encapsulated in microspheres in the 105 -710 mu m size ran by a modified emulsion vulcanization technique, wit h a 100% entrapment efficiency. The external and internal morphology o f microspheres, and the size distribution of PCP-NAM particles dispers ed therein are evaluated by scanning electron micrography. Microsphere s are eluted 9 h with simulated GI fluids (pH 1.2-7.4). Assessment of the rime exponent characterizing the release kinetics, together with r elease and swelling data from planar matrices of same formulation as t he microspheres, substantiate the following release mechanism. Due to their small size, the osmotically active particles have a limited abil ity to crack the silicone polymer and interconnect upon swelling, so t he hydrogel route of release is of a minor relevance, and so is the hy drogel pH-sensitivity. Drug release is mainly governed by partitioning -diffusion in the silicone continuum of microspheres, therefore it is pH-independent and the time exponent is close to the value typical of Fickian release. It is concluded that encapsulation of hydrogel partic les of larger size is a necessary condition for a pH-controlled releas e pattern. (C) 1997 Elsevier Science B.V.