title: Efavirenz dissolution enhancement III: Colloid milling, pharmacokinetics and electronic tongue evaluation.
abstract: 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.
authors.affiliation: Instituto de Tecnologia em Fármacos/Farmanguinhos (FIOCRUZ), Laboratório de Sistemas Farmacêuticos Avançados (LaSiFA), Av. Comandante Guaranys 447, CEP 22775-903 Rio de Janeiro, RJ, Brazil.
authors.forename: Cristiane R D
authors.initials: CR
authors.lastname: Hoffmeister
authors.affiliation: Universidade Federal de Santa Catarina, Laboratório de Controle de Qualidade, Campus Universitário, Trindade, CEP 88040-9007 Florianópolis, SC, Brazil.
authors.forename: Cinira
authors.initials: C
authors.lastname: Fandaruff
authors.affiliation: Instituto de Tecnologia em Fármacos/Farmanguinhos (FIOCRUZ), Laboratório de Sistemas Farmacêuticos Avançados (LaSiFA), Av. Comandante Guaranys 447, CEP 22775-903 Rio de Janeiro, RJ, Brazil.
authors.forename: Maíra A
authors.initials: MA
authors.lastname: da Costa
authors.affiliation: Universidade Federal do Rio de Janeiro, LabTIF, Rio de Janeiro, RJ, Brazil.
authors.forename: Lucio M
authors.initials: LM
authors.lastname: Cabral
authors.affiliation: Vice-Diretoria de Ensino, Pesquisa e Inovação (VDEPI), Farmanguinhos (FIOCRUZ), Brazil.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Pitta
authors.affiliation: Laboratório Nacional de Nanotecnologia para o Agronegócio (LNNA), Embrapa Instrumentação, São Carlos, SP, Brazil; Centro de Ciências Exatas e de Tecnologia (CCET), Universidade Federal de São Carlos, Campus São Carlos, São Carlos, SP, Brazil.
authors.forename: Stanley E R
authors.initials: SE
authors.lastname: Bilatto
authors.affiliation: Instituto de Tecnologia em Fármacos/Farmanguinhos (FIOCRUZ), Laboratório de Sistemas Farmacêuticos Avançados (LaSiFA), Av. Comandante Guaranys 447, CEP 22775-903 Rio de Janeiro, RJ, Brazil.
authors.forename: Livia D
authors.initials: LD
authors.lastname: Prado
authors.affiliation: Laboratório Nacional de Nanotecnologia para o Agronegócio (LNNA), Embrapa Instrumentação, São Carlos, SP, Brazil; Centro de Ciências Exatas e de Tecnologia (CCET), Universidade Federal de São Carlos, Campus São Carlos, São Carlos, SP, Brazil.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Corrêa
authors.affiliation: Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Tasso
authors.affiliation: Universidade Federal de Santa Catarina, Laboratório de Controle de Qualidade, Campus Universitário, Trindade, CEP 88040-9007 Florianópolis, SC, Brazil.
authors.forename: Marcos Antônio S
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Instituto de Tecnologia em Fármacos/Farmanguinhos (FIOCRUZ), Laboratório de Sistemas Farmacêuticos Avançados (LaSiFA), Av. Comandante Guaranys 447, CEP 22775-903 Rio de Janeiro, RJ, Brazil; Universidade Federal do Rio de Janeiro, LabTIF, Rio de Janeiro, RJ, Brazil. Electronic address: helveciorocha@far.fiocruz.br.
authors.forename: Helvécio V A
authors.initials: HV
authors.lastname: Rocha
mesh_terms: D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000737:chemistry* / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003102:Colloids / Q000737:chemistry*; D003521:Cyclopropanes; D004339:Drug Compounding; D062609:Electronic Nose; D005612:Freeze Drying / Q000379:methods; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013535:Suspensions / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003102:Colloids; D003521:Cyclopropanes; D011208:Powders; D013535:Suspensions; D012967:Sodium Dodecyl Sulfate; D002482:Cellulose; C008079:hydroxypropylcellulose; C098320:efavirenz
keywords: Bioavailability; Colloid milling; Dissolution; Drying; Efavirenz; Electronic tongue