title: Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.
abstract: Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus®at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus®, when protected from moisture.
authors.affiliation: a Mines Albi, CNRS , Centre RAPSODEE, Campus Jarlard, Université de Toulouse , Albi , France.|b Department of Pharmaceutics Sciences, Faculty of Pharmacy , Federal University of Pernambuco , Pernambuco , PE , Brazil.
authors.forename: Zênia Maria Maciel
authors.initials: ZM
authors.lastname: Lavra
authors.affiliation: b Department of Pharmaceutics Sciences, Faculty of Pharmacy , Federal University of Pernambuco , Pernambuco , PE , Brazil.
authors.forename: Davi
authors.initials: D
authors.lastname: Pereira de Santana
authors.affiliation: a Mines Albi, CNRS , Centre RAPSODEE, Campus Jarlard, Université de Toulouse , Albi , France.
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Ré
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003521:Cyclopropanes; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D004355:Drug Stability; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011145:Polyvinyls / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004337:Drug Carriers; D011145:Polyvinyls; D018894:Reverse Transcriptase Inhibitors; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; C098320:efavirenz
keywords: Efavirenz; amorphous; dissolution; drug solubility; solid dispersion; spray drying; stability