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Fandaruff C.,Federal University of Santa Catarina | Segatto Silva M.A.,Federal University of Santa Catarina | Galindo Bedor D.C.,Federal University of Pernambuco | De Santana D.P.,Federal University of Pernambuco | And 7 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2015

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). © 2015 Elsevier B.V.


PubMed | Federal University of Rio de Janeiro, Institute Tecnologia em Farmacos Farmanguinhos FIOCRUZ, Vice Diretoria de Ensino, Federal University of São Carlos and 2 more.
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2017

Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is part of first-line therapy for the treatment of human immunodeficiency virus type 1 infection (HIV-1/AIDS). This drug shows relatively low oral absorption and bioavailability, as well as high intra- and inter-subject variability. Several studies have shown that treatment failure and adverse effects are associated with low and high EFV plasma concentrations, respectively. Some studies suggest different EFV formulations to minimize inter-patient variability and improve its solubility and dissolution; however, all of these formulations are complex, using for instance, cyclodextrins, dendrimers and polymeric nanoparticles, rendering them inviable industrially. The aim of this work was to prepare simple and low-cost suspensions of EFV for improvement of solubility and dissolution rate by using colloid mill, spray or freeze-drying, and characterization of the powders obtained. The results demonstrated an increase in the dissolution rate of EFV, using 0.2% of sodium lauryl sulfate (SLS) and 0.2% of hydroxypropylcellulose (HPC) or hydroxypropylmetilcellulose (HPMC) in both freeze and spray dried powders. The pharmacokinetic studies demonstrated improved pharmacokinetic parameters for the formulation containing SLS and HPC. The powders obtained, which present enhanced dissolution properties, can be incorporated in a solid dosage form for treatment of AIDS in paediatric patients with promising results.


PubMed | University of Trento, Elettra - Sincrotrone Trieste, Institute Tecnologia em Farmacos Farmanguinhos FIOCRUZ, Federal University of Santa Catarina and 2 more.
Type: | Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | Year: 2015

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).


Fandaruff C.,Federal University of Santa Catarina | Rauber G.S.,Federal University of Santa Catarina | Araya-Sibaja A.M.,University of Costa Rica | Pereira R.N.,Federal University of Santa Catarina | And 7 more authors.
Crystal Growth and Design | Year: 2014

Polymorphs, cocrystals, solvates, and hydrates have been reported for efavirenz (EFV), which is part of high activity antiretroviral therapy (HAART), and it is considered to be the best choice in the treatment of adults and children. However, studies about thermodynamic stability and improvement of dissolution properties have been rarely reported for the anhydrous polymorphic forms. Therefore, the aim of this work was to characterize the solid state of anhydrous polymorph I and polymorph II (herein obtained), to study the thermodynamic stability and strategies to improve the dissolution properties. In addition, techniques such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), hot stage microscopy (HSM), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), raman spectroscopy (RS), theoretical calculations, and solid-state nuclear magnetic resonance (ss-NMR) were used to complete this work. Thermodynamic studies showed that polymorphs I and II are enantiotropically related with the isoenergetic point between 35 and 40 °C. The EFV polymorph II showed itself to be more stable and 10-fold more soluble than polymorph I, due to modifications of morphology. Therefore, polymorph II could be an excellent candidate with significant advantages for pharmaceutical formulations. © 2014 American Chemical Society.


Fandaruff C.,Federal University of Santa Catarina | Araya-Sibaja A.M.,University of Costa Rica | Pereira R.N.,Federal University of Santa Catarina | Hoffmeister C.R.D.,Institute Tecnologia em Farmacos Farmanguinhos FIOCRUZ | And 2 more authors.
Journal of Thermal Analysis and Calorimetry | Year: 2014

Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, was approved for the treatment of human immunodeficiency virus type 1 infection (HIV-1), and it is used in the high activity antiretroviral therapy in association with others drugs as the best choice of treatment in adults and children. EFV was investigated about its thermal behavior, through DSC, TG, and DTG techniques, and the kinetic parameters were evaluated by isothermal and non-isothermal conditions by Ozawa's conventional method and by an isoconversional method proposed by Ozawa-Flynn-Wall. The decomposition process was obtained by thermogravimetric curves to determine the kinetic. EFV was melted at T peak = 411.66 K, and the decomposition started at 528.97 K. The activation energy values obtained were 93.24 and 91.58 kJ mol -1 for the non-isothermal and isothermal conditions, respectively, with the conventional method. The activation energy values obtained by isoconversional method were practically constant, hence the reaction involves a single step. © 2013 Akadémiai Kiadó, Budapest, Hungary.

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