International Journal of Pharmaceutics 2014-12-30

Asenapine maleate in situ forming biodegradable implant: an approach to enhance bioavailability.

Amelia M Avachat, Sayali S Kapure

文献索引：Int. J. Pharm. 477(1-2) , 64-72, (2014)

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摘要

Biodegradable injectable in-situ forming implants (ISFI) correspond to an alternative parenteral depot system to microspheres and surgical implants. Objective of present work was to formulate and evaluate long acting implant of asenapine maleate (ASM) using PLGA which would release drug uniformly for 21 days. PLGA 50:50 with different drug: polymer ratios were tried. N-methyl-2-pyrrolidone and dimethyl sulphoxide were used as organic solvents. The influence of various parameters viz. polymer concentration, solvent ratio, viscosity and morphology on formation of implant was investigated. In-vitro dissolution studies indicated that drug: polymer ratio of 1:2 and N-methyl-2-pyrrolidone (0.3ml) gave desired release profile, total cumulative drug released being 97.66% at the end of 21 days. Mathematical models point towards erosion mechanism with zero order kinetics. Ex-vivo studies confirmed the formation of implant in extensor digitorum muscle with desired drug release profile. In-vivo study was performed in Sprague- Dawley rats. Compared to marketed sublingual formulation area under curve of ASM implant was found to increase 2.215 fold. The Cmax was found to be 11ng/ml. Thus long acting ISFI of ASM was successfully formulated showing improved therapeutic results for the treatment of schizophrenia and bipolar disorders which could be a potentialsubstitute to marketed sublingual tablets.Copyright © 2014. Published by Elsevier B.V.