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

作者：Nart Viviane; Franca Maria Terezinha; Anzilaggo Daiane; Riekes Manoela Klueppel; Kratz Jadel Mueller; Maduro de Campos Carlos Eduardo; Oliveira Simoes Claudia Maria; Stulzer Hellen Karine^*

来源：Materials Science and Engineering: C , 2015, 53: 229-238.

DOI：10.1016/j.msec.2015.04.028

• Acyclovir
• Solid dispersion
• Ball milling
• Dissolution rate
• Intestinal permeability

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 acydovir'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 acydovir through the development of ball milling solid dispersions with the hydrophilic carriers Pluronic F68 (R), hydroxypropylmethyl cellulose K100M (R) 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 (R) 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 acydovir with superior biopharmaceutical properties.

• 出版日期2015-8-1