Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162280 | Journal of Pharmaceutical Sciences | 2014 | 8 Pages |
Abstract
In this study, we investigated the potential of supersaturation for the formulation of the poorly waterâsoluble microbicide dapivirine (DPV) in an aqueous vaginal gel in order to enhance its vaginal tissue uptake. Different excipients such as hydroxypropylmethylcellulose, polyethylene glycol 1000, and cyclodextrins were evaluated for their ability to inhibit precipitation of supersaturated DPV in the formulation vehicle as such as well as in biorelevant media. In vitro permeation assessment across HECâ1A cell layers demonstrated an enhanced DPV flux from supersaturated gels compared with suspension gels. The best performing supersaturated gel containing 500 μM DPV (supersaturation degree of 4) in the presence of sulfobutyl etherâbetaâcyclodextrin (2.5%) appeared to be stable for at least 3 months. In addition, the gel generated a significant increase in vaginal drug uptake in rabbits as compared with suspension gels. We conclude that supersaturation is a possible strategy to enhance the vaginal concentration of hydrophobic microbicides, thereby increasing permeation into the vaginal submucosa. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3696-3703, 2014
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Carolien Grammen, Jakob Plum, Jeroen Van Den Brande, Nicolas Darville, Koen Augustyns, Patrick Augustijns, Joachim Brouwers,