Micelles entrapped microparticles technology: a novel approach to resolve dissolution and bioavailability problems of poorly water soluble drugs

Abstract

Aim: Aim of this study was to design a solid oral delivery system for a weakly basic drug such as dasatinib (DAS), so as to achieve pH-independent dissolution and improved oral bioavailability.

Methods: DAS was solubilised using sodium lauryl sulphate as an aqueous micellar system and such a system containing lactose monohydrate as carrier was spray-dried to obtain a solid mass. Subsequently, the DAS-solid was converted into a tablet using conventional tableting methods.

Results: The dissolution study revealed pH-independent dissolution over a wide range of pH conditions. An in vivo bioavailability testing on rats revealed an improved C_max and AUC_0–24. Similarly, viability assay showed a better inhibitory effect of spray-dried dasatinib over the DAS.

Conclusions: Micellar solubilisation and spray-drying technology can be approached to resolve poor dissolution and bioavailability of drugs belonging to biopharmaceutical classification system II and III. This technology is amenable to scale-up and has commercial potential.

Keywords:

• Anti-cell proliferation activity
• bioavailability
• dasatinib
• dissolution
• micellar solubilisation
• microparticles
• spray-drying

Acknowledgements

The authors thank the management of Natco Pharma Limited for supporting this work. The technical service from the analytical division and cell biology division of Natco Research Centre is gratefully acknowledged. The authors also would like to thank Mr. Nannapaneni Venkaiah Chowdary, Chairman cum Managing Director, Natco Pharma Limited, Hyderabad, India for permitting the research work and utilising the full-fledged facility and Dr. P. Narmada for her substantial support for the bioavailability study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.