Fast dissolving β-lapachone particles and tablets: an approach using surface adsorption technique

Abstract

Background: β-lapachone (βLAP) is obtained from natural resources with promising preliminary results against the etiologic agent of Chagas disease. βLAP activity is associated with generation of free radical and inhibition of nucleic acids and protein synthesis leading an outstanding antichagasic action. Low water solubility and large therapeutic doses constitute the main problems to overcome in the development of dosage forms of this drug.

Objective: The purpose of the present research was to enhance the limited dissolution rate of βLAP by promoting the spontaneous crystalline growth of βLAP on the surface of an inert excipient.

Methods: Physicochemical characterization of the particles was carried out as well as the drug dissolution rate. Drug adsorbed particles were compared to the drug as supplied and its physical mixtures with the inner excipient. The utility of the βLAP adsorbed particles in the development of tablets obtained by direct compression were also evaluated.

Results: Particles produced by spontaneous crystalline growth of βLAP on microcrystalline cellulose (MCC) hydrophilic surface showed mean diameters between 55–65 µm and fast drug dissolution rate (90% drug dissolved at 50 min). Neither physical nor chemical instability of the drug were detected after the drug adsorption procedure. The compression process does not extensively deteriorate the dissolution behaviour of the systems when an adequate compression pressure is used.

Conclusions: Surface adsorption technique offers a simple way to produce βLAP powder and tablets with improved dissolution rate for oral administration.

Keywords::

• β-Lapachone
• surface adsorption technique
• microcrystalline cellulose
• dissolution rate
• tablets

Acknowledgements

Authors thank LAFEPE, Brazil, and Professor Dr Pedro Jose Rolim Neto, Federal University of Pernambuco, Brazil, for their kind gift of the βLAP and Ms. J. Menis for her help in the correction of the English version of the work.

Declaration of interest

This work was supported by Xunta de Galicia (PGIDIT08CSA007203PR) and the Programme Alβan, the European Union Programme of High Level Scholarships for Latin America, scholarship n° E04D043994BR. ML thanks the Spanish MEC for their financial support (PR2010-0460) during the sabbatical year at Faculty of Science, University of Utrecht (The Netherlands). The authors report no declarations of interest.