Chunsheng Gao
Beijing Institute of Pharmacology and Toxicology, China
Title: Drug itself acting as a pore former in coated pellets for a zero-order release: opportunity and challenge
Biography
Biography: Chunsheng Gao
Abstract
Drug release from ethylcellulose (EC)-coated pellets exhibits a lag phase – a slow or non-release phase in the first 1-2 hours. The objective of the present study was to evaluate the feasibility of using model drug metoprolol succinate (MS) as a pore former to modify the initial lag phase. MS-layered cores with high drug-layering efficiency (97%, w/w) were first prepared by spraying a highly concentrated drug aqueous solution (60% w/w, 70 °C) on non-pareils without using other binders. The presence of MS in EC coating solution significantly improved the coating process by reducing pellets sticking, which often occurs during organic coating. The overall in vitro and in vivo drug release rates from EC/MS and EC/hydroxypropylcellulose (HPC)-coated pellets were comparable. However, the initial lag phase associated with EC/HPC coating was not observed from EC/MS-coated pellets, which was further confirmed by in vivo drug release in beagle dogs. There may be a maximum physical compatibility of MS with EC, and the physical state of the drug in the functional coating layer of EC/MS (80:20) was simultaneously crystalline and non-crystalline. The functional coating layer with MS as a pore former was not completely stabilized without curing. Curing at 60 °C for 1 day could substantially improve the stability of EC/MS-coated pellets. The physical state of the drug in the free film of EC/MS (85:15) changed partially from amorphous to crystal when cured at 60 °C for 1 day, which should be attributed to the incompatibility of the drug with EC.