Physicochemical characterisation of spray dried ternary solid dispersions of simvastatin. Processability, tableting and dissolution.

Abstract

Simvastatin(SMV) is poorly soluble drug classified as belonging to Class II of BiopharmaceuticsClassification System. Common approach to improve apparent solubility of drugsis production of amorphous solid dispersions (ASD) by means of spray drying(SD) or hot-melt extrusion. Spray drying of low-glass transition temperature(Tg) ASDs is challenging due to the risk of material being exposed to SD outlettemperatures close to its Tg which may result in melting of ASD and subsequentcrystallisation of amorphous drug. It was hypothesised that addition ofeasily-crystallising material to ASD will improve its SD processability. Inaddition, it was hypothesised that produced ternary solid dispersions (TSD)composed of amorphous composite of drug and the polymer (PVP K17, 55 and 150) andcrystalline, soluble nanoparticles (NaCl) will improve dissolution of TSDtablets.  The dissolution of SMV fromTSDs was faster compared with that of binary solid dispersion in case of SMV-TSDsproduced with PVP K55 and 150. The tabletabilityassessment showed increase in compression led to increase in tensile strengthand decrease in porosities of SDs tablets.