Screening, characterization and evaluation for novel crystal forms from antiretroviral and antineoplastic drugs

• Grant number: 07/07185-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2008
• Effective date (End): October 31, 2010
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Javier Alcides Ellena
• Grantee: Felipe Terra Martins
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

This research proposal, Screening, characterization and evaluation for novel crystal forms from antiretroviral and antineoplastic drugs, is sought to synthesis of unpublished polymorphic forms from drugs that have been widely used for the antiretroviral and antineoplastic therapies, followed by characterization of its physical and chemical properties at the solid state and evaluation of the solubility and pharmaceutical dissolution. For this purpose, antiretroviral drugs belonging to the inhibitor classes targeted on reverse transcriptase, both nucleoside and nonnucleoside compounds, and aspartate HIV protease, as well as antineoplastic drugs from alkylating agents and antifolate classes will be crystallized by mean of several methods in order to obtain polymorphs different from those reported in the literature until this moment. After the crystallization step, the obtained crystalline materials will be analyzed by photonic and scanning electron microscopy, X-ray single crystal and powder diffraction, Fourier Transform infrared and Raman vibrational spectroscopy, thermogravimetry and differential scanning calorimetry. Once the novel polymorphic forms from the tested drugs have been identified, these samples and reference drugs at the crystalline forms previously described in the literature will be evaluated comparatively in solubility and dissolution experiments. (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)

MARTINS, FELIPE T.; PAPARIDIS, NIKOLAS; DORIGUETTO, ANTONIO C.; ELLENA, JAVIER. Crystal Engineering of an Anti-HIV Drug Based on the Recognition of Assembling Molecular Frameworks. Crystal Growth & Design, v. 9, n. 12, p. 5283-5292, DEC 2009. (07/07185-5)

MARTINS, FELIPE T.; DORIGUETTO, ANTONIO C.; ELLENA, JAVIER. From Rational Design of Drug Crystals to Understanding of Nucleic Acid Structures: Lamivudine Duplex. Crystal Growth & Design, v. 10, n. 2, p. 676-684, FEB 2010. (07/07185-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARTINS, Felipe Terra. Supramolecular chemistry of antiretroviral nucleoside reverse transcriptase inhibitor drugs. 2010. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.