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Ashlesha P. Pandit,Tushar T. Chavan,Kishanchandra R. Khandelwal 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.6
The objective of present investigation was to enhance solubility, dissolution rate and bioavailability of poorly water soluble drug atorvastatin using solid lipid glycerol monostearate and surfactant poloxamer-407. Oral pastilles of glycerol monostearate and poloxamer were formulated by pastillation technique and optimized by central composite design. Hemispherical pastilles were evaluated for drug content, saturation solubility study, thermal properties and in vitro, ex vivo and in vivo drug release study. Formulation F4 at high level of glycerol monostearate (1000 mg) and poloxamer-407 (400 mg) showed 25-fold and 3-fold increased in solubility and dissolution rate, respectively. X-Ray diffraction and scanning electron microscopic study proved the decrease in crystallinity of atorvastatin and confirmed the conversion of crystalline to amorphous form, respectively. Ex vivo study revealed that maximum amount of released drug was absorbed through the everted intestine. In vivo study in rats showed higher HMG CoA to mevalonate ratio of pastilles than plain drug. This indicated better bioavailability and hyperlipidemic activity of pastilles than atorvastatin. Thus, the solubility, dissolution rate and bioavailability of atorvastatin were enhanced successfully using lipid carrier system.