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Microstructural effects of high-energy grinding on poorly soluble drugs: the case study of efavirenz

Published online by Cambridge University Press:  21 February 2017

Elisa Cappelletto ,
Luca Rebuffi ,
Alberto Flor  and
Paolo Scardi
Elisa Cappelletto*
Affiliation:
Department of Civil, Environmental and Mechanical Engineering, University of Trento, via Mesiano 77, 38123 Trento, Italy
Luca Rebuffi
Affiliation:
Elettra-Sincrotrone Trieste, Area Science Park, Basovizza, 34149 Trieste, Italy
Alberto Flor
Affiliation:
Department of Civil, Environmental and Mechanical Engineering, University of Trento, via Mesiano 77, 38123 Trento, Italy
Paolo Scardi
Affiliation:
Department of Civil, Environmental and Mechanical Engineering, University of Trento, via Mesiano 77, 38123 Trento, Italy
*
a)Author to whom correspondence should be addressed. Electronic mail: elisa.cappelletto@unitn.it
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Abstract

In this work, a poorly water-soluble drug (efavirenz) was mechanically activated by ball-milling. The effect of the mechanical activation on the dissolution behavior was investigated considering changes in the particle size and morphology. The powder diffraction was used to follow the comminution process, verifying phase compositions, and crystalline domain size. The interplay between domain and grain size was studied in relation to the solubility rate, through specific dissolution tests. Finally, the morphological characterization has allowed to complete the physical–chemical characterization of the milled powders. This study demonstrated that the mechanical activation of the drug leads the particle size reduction and, with a long milling time, morphological changes. The grain size reduction is not always sufficient to increase the solubility: morphology and agglomeration grade play an important role in the dissolution process.

Keywords

Efavirenznanosizingcrystalline domain sizecomminution processesdissolutionball milling
Type
Technical Articles
Information
Powder Diffraction , Volume 32 , Supplement S1 , September 2017 , pp. S135 - S140
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Copyright
Copyright © International Centre for Diffraction Data 2017 

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References

Assis da Costa, M., Cardoso Seiceira, R., Rangel Rodrigues, C., Rodrigues Drago, C., Mendes Cabral, L., and Antunes Rocha, H. V. (2013). “Efavirenz dissolution enhancement I: co-micronization,” Pharmaceutics 5, 1–22.Google Scholar
Campos de Melo, A. C., Ferreira de Amorim, I., de Lima Cirqueira, M., and Martins, F. T. (2013). “Toward novel solid-state forms of the anti-HIV drug efavirenz: from low screening success to cocrystals engineering strategies and discovery of a new polymorph,” Cryst. Growth Des. 13, 1558–1569.Google Scholar
Chogale, M. M., Ghodake, V. N., and Patravale, V. B. (2016). “Performance parameters and characterizations of nanocrystals: a brief review,” Pharmaceutics 8(26), 1–18.Google Scholar
Costa Pinto, E., Mendes Cabral, L., and Pereira de Sousa, V. (2014). “Development of a discriminative intrinsic dissolution method for efavirenz,” Dissolution Technol. 21, 31–40.Google Scholar
Dizaj, S. M., Vazifehasl, Z., Salatin, S., Adibkia, K., and Javadzadeh, Y. (2015). “Nanosizing of drugs: effect on dissolution rate,” Res. Pharm. Sci. 10(2), 95–108.Google Scholar
Hansa, D., Giocobbe, C., Perisutti, B., Voinovich, D., Grassi, M., Cervellino, A., Masciocchi, N., and Guagliardi, A. (2015). Nanostructured drugs embedded into a Polymeric Matrix: Vinpocetine/PVP Hybrid investigated by Debye Function Analysis, Molecular Pharmaceutics. 13(9), 3024–3042.Google Scholar
Kolhe, S., Chaudhari, P. D., and More, D. (2014). “Dissolution and bioavailability enhancement of efavirenz by hot melt extrusion technique,” J. Pharm. 4(5), 2319–4219.Google Scholar
Loh, Z. H., Samanta, A. K., and Heng, P. W. S. (2015). “Overview of milling techniques for improving the solubility of poorly water-soluble drugs,” Asian J. Pharm. Sci. 10, 255–274.CrossRefGoogle Scholar
Mahapatra, A. K. and Murthy, P. N. (2014). “Solubility and dissolution rate enhancement of efavirenz by inclusion complexation and liquid anti-solvent precipitation technique,” J. Chem. Pharm. Res. 6(4), 1099–1106.Google Scholar
Mosharraf, M. and Nystrom, C. (1995). “The effect of particle size and shape on the surface specific dissolution rate of microsized practically insoluble drugs,” Int. J. Pharm. 122, 35–47.Google Scholar
Rasenack, N. and Muller, B. W. (2003). “Micron-size drug particles: common and novel micronization techniques,” Pharm. Dev. Technol. 9(1), 1–13.Google Scholar
Rebuffi, L., Plaisier, J. R., Abdellatief, M., Lausi, A., and Scardi, P. (2014). “MCX: a synchrotron radiation beamline for x-ray diffraction line profile analysis,” Z. Anorg. Allg. Chem. 640, 3100–3106.CrossRefGoogle Scholar
Scardi, P., Ortolani, M., and Leoni, M. (2010). “WPPM: microstructural analysis beyond the Rietveld method,” Mater. Sci. Forum 651, 155–171.Google Scholar
Schneider, C. A., Rasband, W. S., and Eliceiri, K. W. (2012). “NIH image to imageJ: 25 years of image analysis,” Nat. Methods 9(7), 671–675.Google Scholar
Sinha, B., Muller, R. H., and Moschwitzer, J. P. (2013). “Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size,” Int. J. Pharm. 453(1), 126–141.CrossRefGoogle ScholarPubMed
Sun, J., Wang, F., Sui, Y., She, Z., Zhai, W., Wang, C., and Deng, Y. (2012). “Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals,” Int. J. Nanomed. 7, 5733–5744.Google Scholar
Tandel, H., Patel, P., and Jani, P. (2015). “Preparation and study of efavirenz microemulsion drug delivary system for enhancement of bioavailability,” Eur. J. Pharm. Med. Res. 2(5), 1156–1174.Google Scholar
Tromba, G., Longo, R., Abrami, A., Arfelli, F., Astolfo, A., Bregant, P., Brun, F., Casarin, K., Chenda, V., Dreossi, D., Hola, M., Kaiser, J., Mancini, L., Menk, R. H., Quai, E., Quai, E., Rigon, L., Rokvic, T., Sodini, N., Sanabor, D., Schultke, E., Tonutti, M., Vascotto, A., Zanconati, F., Cova, M., and Castelli, E. (2010). “The SYRMEP beamline of elettra: clinical mammography and bio-medical applications,” AIP Conf. Proc. 1266(1), 18–23.Google Scholar