Utility of plasticised polymer in solid dispersions for solubility enhancement of thermosensitive and poorly soluble API

Abstract

Background/objectiveDespite sophisticated technique as hot melt extrusion has established its place in formation of amorphous molecular dispersions, the advantage of which can't be extrapolated to thermosensitive poorly soluble API, like Acetazolamide, because of inherent formulation problems such as degradation and/or browning following melting, residual crystallinity if processed at lower temperature than its melting point and processing problems such as poor extrudability. Thus the present study interestingly explores a stepwise approach to obtain solubility enhanced, thermodynamically stable amorphous molecular dispersions of thermosensitive drugs by hot melt extrusion technique. MethodsSolid dispersions of Acetazolamide with a polymethacrylate solubiliser in 1:1 and 1:2 weight ratios and with a solubiliser and a plasticiser in 1:2:0.15 and 1:2:0.30 weight ratios were prepared by hot melt extrusion and studied for drug content, thermal degradation, molecular interactions, solid state characterisation, solubility characteristics and subsequently accelerated stability study. ResultsThe formulation and the processing problems associated with solid dispersions of Acetazolamide with a solubiliser were overcome by coprocessing their optimised proportion with appropriate proportion of plasticiser, giving completely amorphous, molecular dispersions of Acetazolamide with markedly enhanced solubility characteristics. During stability study, the optimised proportion of solid dispersions reported only an insignificant change in solubility characteristics and amorphous nature of the drug. ConclusionThus, the study provided formulation strategies in a stepwise manner to enhance solubility characteristics of a poorly soluble API showing thermal degradation when processed by hot melt extrusion.