ABSTRACT

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.