title: Ball-milled solid dispersions of BCS Class IV drugs: Impact on the dissolution rate and intestinal permeability of acyclovir.
abstract: Acyclovir, an analog of 2'-deoxyguanosine, is one of the most important drugs in the current approved antiviral treatment. However, it's biopharmaceutical properties, contribute to acyclovir's poor oral bioavailability, which restricts the clinical use of the drug. In this view, the aim of this work was to improve the dissolution rate and intestinal permeability of acyclovir through the development of ball milling solid dispersions with the hydrophilic carriers Pluronic F68®, hydroxypropylmethyl cellulose K100M® and chitosan. Solid dispersions were obtained and completely characterized through different solid state techniques. The solid state data demonstrated a decrease in the crystallinity (amorphous phase and defects) and the presence of hydrogen bonds for SD HPMC and SD CTS. The enhancement of dissolution rates was observed for all SDs developed. In addition, no detrimental effects over the in vitro antiviral activity were detected. The solid dispersions with Pluronic F68® significantly improved the intestinal permeability of acyclovir across Caco-2 cells. In summary, the SDs developed in this study could be considered as potential systems for solid dosage forms containing acyclovir with superior biopharmaceutical properties.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: Nart
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: França
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Daiane
authors.initials: D
authors.lastname: Anzilaggo
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Manoela Klüppel
authors.initials: MK
authors.lastname: Riekes
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Jadel Müller
authors.initials: JM
authors.lastname: Kratz
authors.affiliation: Departamento de Física, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Carlos Eduardo Maduro
authors.initials: CE
authors.lastname: de Campos
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil.
authors.forename: Cláudia Maria Oliveira
authors.initials: CM
authors.lastname: Simões
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis 88040-970, Brazil. Electronic address: hellen.stulzer@gmail.com.
authors.forename: Hellen Karine
authors.initials: HK
authors.lastname: Stulzer
mesh_terms: D000212:Acyclovir / Q000737:chemistry* / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D065569:Gastrointestinal Absorption; D006801:Humans; D008954:Models, Biological; D010539:Permeability
chemical_list: D004337:Drug Carriers; D000212:Acyclovir
keywords: Acyclovir; Ball milling; Dissolution rate; Intestinal permeability; Solid dispersion