Ball-milled solid dispersions of BCS Class IV drugs: Impact on the dissolution rate and intestinal permeability of acyclovir

• Published in: Materials Science & Engineering C Vol. 53; pp. 229 - 238
• Main Authors: Nart, Viviane, França, Maria Terezinha, Anzilaggo, Daiane, Riekes, Manoela Klüppel, Kratz, Jadel Müller, de Campos, Carlos Eduardo Maduro, Simões, Cláudia Maria Oliveira, Stulzer, Hellen Karine
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2015
• Subjects: Acyclovir; Acyclovir - chemistry; Acyclovir - pharmacokinetics; Ball milling; Caco-2 Cells; Chitosan; Dispersions; Dissolution; Dissolution rate; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Drugs; Gastrointestinal Absorption; Humans; Intestinal permeability; Materials science; Models, Biological; Permeability; Solid dispersion; Solid state; Ball milling; Solid dispersion; Acyclovir; Dissolution rate; Intestinal permeability
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2015.04.028

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. [Display omitted] •Acyclovir solid dispersion prepared by ball milling technique•Improvement of acyclovir dissolution properties by ball-milled solid dispersions•Improvement intestinal permeability available across Caco-2 cell