Abstract:

The aim of this study was to investigate effects of solvent type on granisetron hydrochloride release from injectable in situ forming implants. Formulations contained 32% poly(DL-lactide-co-glycolide) 50:50 (Resomer RG 502), 64% solvent and 4% drug by weight. Dimethylsulphoxide (DMSO), N-methyl-2pyrrolidone (NMP), tetraglycol (TG), propylene carbonate (PC), triacetin (TA) and benzyl benzoate (BB) in the rank of decreasing hydrophilicity, were used as solvents. After determination of formulation`s injectability through 20G needles, in vitro dissolution test was carried out in a shaker bath (30 rpm) and samples were analyzed by spectrophotometrically. Drug release profiles showed that initial burst decreased by using hydrophobic solvents in rank of BB>TA>PC and increased by using hydrophilic solvents in rank of DMSO>NMP>TG. For following release; DMSO caused a burst (99.1%) while BB and TA caused very slow release for the first week. BB and TA showed tri-phased profiles for three weeks. NMP and TG gave similar profiles between DMSO and PC. PC gave relatively regular drug release after 25% in the first day. Dissolution kinetics mostly fitted to Higuchi kinetic model. Results showed that, combination of phase sensitive polymers and moderately hydrophobic solvents can be utilized for modifying release of drug from injectable implant systems for 21 days

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