In this study, effects of solvent combinations on granisetron HCl release from injectable in situ forming implants (ISFIs) were investigated. Solvents having decreasing hydrophilicities in the rank of dimethylsulphoxide (DMSO), N-methyl-2-pyrrolidone (NMP) and prophylene carbonate (PC) were used in 1:1 combination with hydrophobic benzyl benzoate (BB). Glycerin (GL), polyethylene glycol 400 (PEG 400) and benzyl alcohol (BA) were used as additives in 1:5 combination with BB. Investigated ISFIs contain 64% solvent, 32% poly(DL-lactide-co-glycolide) (Resomer RG 502) and 4% drug. In vitro dissolution test was carried out in a shaker bath (30 rpm and 37°C) and samples were analyzed by UV spectrophotometer. Drug release and initial burst increased by using solvent systems in the rank of BB:DMSO>BB:NMP>BB:PC and also increased by using solvent-additive systems in the rank of BB:GL>BB:PEG 400>BB:BA. Though solvent systems gave lower initial burst of drug, they caused irregular release profiles compared to solvent-additive systems while BB alone gave a sigmoid like release profile with lowest initial burst. Between all formulations better release profile (initial burst 19.15% in the first day) was obtained with BB. BA system. According to kinetic evaluation, formulations containing solvent systems best fitted to Korsmeyer-Peppas while formulations containing solvent-additive systems fitted to Higuchi kinetic model best. As a conclusion it was observed that hydrophobic solvent combinations could be useful to control the release of drug from in situ forming implant systems.

Keywords: Phase sensitive, Injectable, In situ implant, Granisetron HCl, Poly(DL-lactide-co-glycolide).