Development of Self-Microemulsifying Drug Delivery Systems of Poorly Water-Soluble Pazopanib for Improvement of Oral Absorption

초록

Self-microemulsifying drug delivery systems represent a stable formulation for enhancing the solubility and absorption efficacy of poorly soluble drugs. In this study, a self-microemulsifying drug delivery system (SMEDDS) was designed and applied for oral administration of poorly water-soluble pazopanib, a Biopharmaceutical Classification Class II anticancer drug. The solubility of pazopanib was first evaluated using various oils, surfactants, and co-surfactants. Pseudoternary phase diagrams were plotted to identify the self-emulsifying region and the phase behavior of optimized vehicle selected after screening of oils, surfactants, and co-surfactants. The SMEDDS comprising Capmul MCM NF, Tween 80, and PEG 400 was fabricated for incorporating pazopanib. It exhibited spherical droplets with size of 86.9 +/- 0.8 nm and zeta potential value of -14.7 +/- 0.1 mV. In vitro dissolution profiles of the SMEDDS were 2.40-fold (pH 4.0) and 6.45-fold (pH 6.8) higher than that of pazopanib powder. In particular, pazopanib-SMEDDS showed pH-independent dissolution profiles. In vivo pharmacokinetic parameters of the SMEDDS revealed enhanced bioavailability of pazopanib, which was 3.32-fold higher than that of pazopanib powder when administered orally. Taken together, the SMEDDS is effective as an oral delivery vehicle for pazopanib. In addition, our findings demonstrate that self-microemulsifying drug delivery systems could be a potential tool for improving bioavailability of other poorly water-soluble drugs.

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