Dissolution and bioavailability enhancement of Atorvastatin: Gelucire semi-solid binary system

Atorvastatin (Atv) is one of antihyperlipidimic drugs characterized by limited oral bioavailability due to its low solubility -despite its high permeability- that hinders its full clinical relevance. Herein, we formulated Atv as a binary system with hydrophilic carrier in hard gelatin capsules to enhance the solubility, dissolution rate and subsequently the bioavailability. Gelucire 44/14® and Gelucire 50/13® were selected as the carriers and the prepared formulae were characterized through solubility measurement, FTIR, DSC, and X-RPD analysis. In vitro dissolution testing and in vivo assessment of the oral bioavailability in New Zealand rabbits were also performed. Atv solubility markedly increased by incorporation with either Gelucire 44/14® or Gelucire 50/13®. FTIR, DSC and X-RPD confirm the successful incorporation of Atv without any chemical alteration or interaction. In vitro dissolution showed that up to 85.8% of Atv dissolution within 15 min. Oral bioavailability of the selected formula (Cmax = 1312 ng/mL and AUC0-t to 11394 ng hr/mL) was higher than Lipitor® (Cmax = 653 ng/mL and AUC0-t = 4584 ng hr/mL) and higher than free Atv (Cmax = 527 ng/mL and AUC0-t = 2546 ng hr/mL). These results revealed that Gelucire® formulation has augmented Atv oral bioavailability and this was correlated to the relative improvement of in vitro dissolution rate.

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