title: Correlation between microstructure and bioequivalence in anti-HIV drug efavirenz.
abstract: Polymorphism and particle size distribution can impact the dissolution behaviour and, as a consequence, bioavailability and bioequivalence of poorly soluble drugs, such as Efavirenz (EFV). Nevertheless, these characteristics do not explain some failures occurring in in vitro assays and in in vivo studies. EFV belongs to Class II and the High Activity Antiretroviral Therapy (HAART) is considered the best choice in the treatment of adults and children. EFV is a drug that needs bioequivalence studies for generic compounds. In this work, six raw materials were analyzed and two of them were utilized with human volunteers (in vivo assays or bioequivalence). All the routine pharmaceutical controls of raw materials were approved; however, the reasons for the failure of the bioequivalence assay could not be explained with current knowledge. The aim of this work was to study microstructure, a solid-state property of current interest in the pharmaceutical area, in order to find an explanation for the dissolution and bioequivalence behaviour. The microstructure of EFV raw materials was studied by Whole Powder Pattern Modelling (WPPM) of X-ray powder diffraction data. Results for different EFV batches showed the biorelevance of the crystalline domain size, and a clear correlation with in vitro (dissolution tests) and in vivo assays (bioequivalence).
authors: Laboratório de Controle de Qualidade, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Cinira
authors: C
authors: Fandaruff
authors: Laboratório de Controle de Qualidade, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors: Marcos Antônio
authors: MA
authors: Segatto Silva
authors: Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, Brazil.
authors: Danilo Cesar
authors: DC
authors: Galindo Bedor
authors: Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, Brazil.
authors: Davi Pereira
authors: DP
authors: de Santana
authors: Laboratório de Sistemas Farmacêuticos Avançados, Instituto de Tecnologia em Fármacos/Farmanguinhos (FIOCRUZ), Rio de Janeiro, Brazil.
authors: Helvécio Vinícius Antunes
authors: HV
authors: Rocha
authors: Department of Civil, Environmental and Mechanical Engineering, University of Trento, Trento, Italy; Elettra-Sincrotrone Trieste, Trieste, Italy.
authors: Luca
authors: L
authors: Rebuffi
authors: Department of Civil, Environmental and Mechanical Engineering, University of Trento, Trento, Italy.
authors: Cristy Leonor
authors: CL
authors: Azanza Ricardo
authors: Department of Civil, Environmental and Mechanical Engineering, University of Trento, Trento, Italy.
authors: Paolo
authors: P
authors: Scardi
authors: Laboratório de Controle de Qualidade, Universidade Federal de Santa Catarina, Florianópolis, Brazil; Pós-Graduação em Engenharia e Ciências dos Materiais, Universidade Federal de São Paulo, São José dos Campos, Brazil. Electronic address: scuffini@unifesp.br.
authors: Silvia Lucia
authors: SL
authors: Cuffini
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D048588:Benzoxazines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003521:Cyclopropanes; D004340:Drug Contamination; D065546:Drug Liberation; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D015394:Molecular Structure; D010316:Particle Size; D033362:Powder Diffraction; D011208:Powders; D015203:Reproducibility of Results; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D017356:Synchrotrons; D013810:Therapeutic Equivalency
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D011208:Powders; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz
keywords: Anti-HIV; Bioequivalence; Efavirenz; Microstructure; Powder diffraction; Synchrotron Radiation