Solid state characterization of anti-HIV drugs: rational design of new crystalline forms

• Grant number: 09/14705-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2009
• End date: November 30, 2011
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Javier Alcides Ellena
• Grantee: Javier Alcides Ellena
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

This research proposal is devoted to synthesize new crystalline forms of drugs that have been widely used in anti-HIV therapy, followed by solid state characterization of their physical and chemical properties. Anti-HIV drugs belonging to the inhibitor classes targeted on reverse transcriptase, both nucleoside and non-nucleoside compounds, and aspartate HIV protease will be subjects of crystallization procedures in order to obtain crystalline modifications with better pharmacokinetic properties than those of solid phases used for incorporation into pharmaceutical oral solid dosage forms. The pharmacokinetic features are improved, mainly, due to changes in dissolution and solubility profiles. Such properties profoundly depend on the drug crystalline phase. Since the nucleoside reverse transcriptase inhibitors are very used in the anti-AIDS drug combinatory medication, the study will be mainly focused on this drug class. Both rational design strategies, in which solvents and co-crystallizing agents are chosen on the basis of molecular and supramolecular aspects of drugs and crystallization adjuvants, and screening procedures, which lead to the discovery of crystalline forms by using trials under different crystallization conditions, will be approached in an attempt to synthesize new crystalline phases of anti-HIV drugs. After the crystallization step, the obtained crystalline materials will be analyzed by photonic and scanning electron microscopy, single crystal and powder X-ray diffraction, Fourier Transform infrared and Raman vibrational spectroscopy, thermogravimetry and differential scanning calorimetry, as well as solubility and dissolution features will be determined. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARTINS, FELIPE T.; LEGENDRE, ALEXANDRE O.; HONORATO, SARA B.; AYALA, ALEJANDRO P.; DORIGUETTO, ANTONIO C.; ELLENA, JAVIER. Solvothermal Preparation of Drug Crystals: Didanosine. Crystal Growth & Design, v. 10, n. 4, p. 1885-1891, APR 2010. (09/14705-0, 07/07185-5)