Mechanical activation of Efavirenz: the effects on the dissolution and inhibitory behavior

Abstract

A poorly water-soluble drug (Efavirenz) was mechanically activated by ball-milling. The effect of the mechanical activation on the dissolution behavior and bioavailability was investigated revealing possible correlations with the grinding action, in terms of crystallinity, particle size and morphology.With proper selection of the grinding parameters the dissolution kinetics can be controlled, both in terms of dissolution velocity and as amount of dissolved drug. In vitro biological tests show that milling does not impair the ability of Efavirenz to inhibit HIV-1 infection (p value >0.05); the IC50 values of ground Efavirenz is indeed lower than values for the pristine micronized powder.

Keywords:

• Bioavailability
• dissolution test
• Efavirenz
• milling
• nanostructure

Acknowledgements

The authors thank Farmanguinhos/Fiocruz for providing the raw materials, and Dr Mirco D’Incau of Univ. of Trento for technical support. We warmly thank Prof. R. Di Maggio and Mrs W. Vaona for the Dynamic Light Scattering DLS measurements, Dr. Jasper R. Plaisier and Dr. Lara Gigli for sharing the effort and for carefully assisting us in performing 2D-XRD measurements at the MCX beamline

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by Project 2013–0247, “Mechanical activation to improve bioavailability and to reduce adverse effects of drugs in the therapy of chronic diseases”, Fondazione Caritro, Trento.