Compression-coated tablets of glipizide using hydroxypropylcellulose for zero-order release: In vitro and in vivo evaluation

摘要

Compression coating, which presents some advantages like short manufacturing process and non-solvent residue over liquid coating, has been introduced to the oral administration systems for decades. The purpose of this study was to design a zero-order release of compression-coated tablets using hydroxypropylcellulose (HPC) as the coating layer and glipizide which was solubilized by manufacturing the inclusion complex of β-cyclodextrin as a model drug. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated by "f2" factor with Glucotrol XL?. The uptake and erosion study, the correlation coefficient (R) and the exponent (n) were used as indicators to justify drug release mechanism. Bioavailability in vivo was determined by administering the compression-coated tablets to rabbits in contrast with Glucotrol XL ?. It was found that the formulation presented a well zero-order behavior at the weight ratio of drug 11:14 (core:layer) and the combination of HPC-L (8.0 mPa s) and HPC-M (350 mPa s) (8:9), with the "f 2" of 66.90. The mechanism for zero-order release of these compression-coated tablets was solvent penetration into the dosage form and drug dissolution from the erosion of the gelled HPC matrix. The parameter AUC 0-∞ of the compression coated tablets and the market tablets were 37,255.93 ± 1474.08 h ng/ml and 43265.40 ± 1015.28 h ng/ml, while the relative bioavailability was 87.66 ± 1.56%. These studies demonstrate that the designed compression-coated tablets may be a promising strategy for peroral controlled release delivery system of water-insoluble drugs.