Computer simulations applied to the development of pharmaceutical oral formulations containing fexofenadine

• Grant number: 18/18766-3
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2019
• End date: July 31, 2021
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marcelo Dutra Duque
• Grantee: Marcelo Dutra Duque
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Leticia Norma Carpentieri Rodrigues ; Michele Georges Issa ; Newton Andréo Filho

Abstract

Fexofenadine is a drug used in the treatment of allergic rhinitis and urticaria. It is a class 3 drug, high soluble and low permeable, according to the Biopharmaceutics Classification System. Fexofenadine exists as two polymorphic forms, form I (anhydrous) and form II (dihydrate). It was reported in the literature that its biopharmaceutics classification is a borderline between classes 3 and 4, depending on the method used to obtain its solubility data. In addition, its intestinal absorption is dependent on the low permeability in enterocytes and intestinal transporters as OATP and P-gp. Considering the complexity involved in the absorption process of fexofenadine when administered orally and the existence of computational tools to predict drug dissolution and absorption, this project has the objective of using simulations by means of the computer programs GastroPlus" and DDDPlus" for the development of tablet and suspensions formulations containing fexofenadine. Some formulations will be obtained, evaluated and the results will be used to fit mathematical parameters in the computer programs, to simulate the other formulations. The simulations will be used to evaluate the influence of the form of the drug used (anhydrous and dihydrate), particle size, formulation processing (tablets obtained by direct compression and by wet granulation) and suspensions on intestinal absorption. It will be estimated, by population simulations, the bioequivalence of the produced formulations in relation to the reference product Allegra®. (AU)