The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.
The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Marijke M M
MM
Dhondt
Els
E
Adriaens
Jens Van
JV
Roey
Jean Paul
JP
Remon
D000282:Administration, Intravaginal; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D007509:Irritants / Q000009:adverse effects*; D009092:Mucous Membrane / Q000187:drug effects*; D011743:Pyrimidines / Q000009:adverse effects*; D011817:Rabbits; D012908:Snails / Q000187:drug effects; D013089:Spermatocidal Agents / Q000009:adverse effects; D018675:Toxicity Tests / Q000379:methods*; D014621:Vagina / Q000187:drug effects*; D014622:Vaginal Creams, Foams, and Jellies / Q000009:adverse effects
D007509:Irritants; D011743:Pyrimidines; D013089:Spermatocidal Agents; D014622:Vaginal Creams, Foams, and Jellies; C481671:Dapivirine