Study of polymorphism of small molecule tyrosine kinase inhibitors

• Grant number: 15/15456-5
• Support type: Scholarships abroad - Research
• Effective date (Start): February 01, 2016
• Effective date (End): January 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Gabriel Lima Barros de Araujo
• Grantee: Gabriel Lima Barros de Araujo
• Host: Stephen R. Byrn
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Local de pesquisa : Purdue University, United States

Abstract

Polymorphism can cause quality deviations during the production of medicines and can influence their effectiveness. Therefore, an understanding of this phenomenon and its implications opens a wide field of possibilities to be explored in the pharmaceutical field, including the emergence of new paradigms and tools for the quality assurance of medicines. Small molecule tyrosine kinase inhibitors (TKIs) represent an extremely promising and rapidly expanding group of antitumor drugs given orally. Although some polymorphism information of these compounds is included in the patents, the basic structural and thermodynamic data are poor in terms of quality of the measurements and differences and misconceptions between the crystals forms reported are evident. Additionally, polymorphism is an important factor that can impact the bioavailability and, consequently, clinical efficacy of those compounds, since most of them have low solubility in water. This project falls within this scope and focuses on: (i) preparation of polymorphs, solvates, or co-crystals of TKIs; (ii) their characterization in terms of structure and thermodynamic stability; (iii) their evaluation in terms of biopharmaceutical performance.

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)

DE ARAUJO, GABRIEL L. B.; BENMORE, CHRIS J.; BYRN, STEPHEN R. Local Structure of Ion Pair Interaction in Lapatinib Amorphous Dispersions characterized by Synchrotron X-Ray diffraction and Pair Distribution Function Analysis. SCIENTIFIC REPORTS, v. 7, APR 11 2017. Web of Science Citations: 4.

ZELLER, MATTHIAS; BARROS DE ARAUJO, GABRIEL LIMA; PARKER, TREV; RAI, AMRINDER SINGH; BYRN, STEPHEN R. A new solvate of afatinib, a specific inhibitor of the ErbB family of tyrosine kinases. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, n. 3, p. 417+, MAR 2017. Web of Science Citations: 0.

DE ARAUJO, GABRIEL L. B.; ZELLER, MATTHIAS; SMITH, DANIEL; NIE, HAICHEN; BYRN, STEPHEN R. Unexpected Single Crystal Growth Induced by a Wire and New Crystalline Structures of Lapatinib. Crystal Growth & Design, v. 16, n. 10, p. 6122-6130, OCT 2016. Web of Science Citations: 1.