Slug species- and population-specific effects on the end points of the Slug Mucosal Irritation test.

The Slug Mucosal Irritation test seems to be a promising method for the evaluation of the local tolerance of products applied to the mucosa. Furthermore, the Slug Mucosal Irritation test is a reliable method to classify chemicals accurately into three eye irritation categories based on the mucus production and the score for tissue damage. Until now the slug Arion lusitanicus collected in Belgium was always used as test organism. The present study investigated the effects of the slug population and species on the end points of the test and on the eye irritation classification. For this purpose, the eye irritation/damage test procedure and eye reference chemicals were used. Comparison of the results of one Belgian and two Swiss A. lusitanicus populations indicated that the geographic and ecological origins of slug populations did neither influence the mucus production, nor the score for tissue damage. Slug species-specific effects on the test end points were investigated by comparing the data of Belgian Limax flavus with corresponding data of Belgian A. lusitanicus. L. flavus produced more mucus than A. lusitanicus, so that the mucus production cut-off values had to be increased. Therefore, the results indicated that the test procedure and prediction model have to be optimised and validated, if other slug species are used instead of A. lusitanicus.

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.

Ocular bioerodible minitablets as strategy for the management of microbial keratitis.

PURPOSE: Evaluation in volunteers of ciprofloxacin-containing ocular gelling minitablets with prolonged release properties. METHODS: The irritation potential of ciprofloxacin-containing bioadhesive powder mixtures, used to prepare ocular bioerodible minitablets, was evaluated with a slug mucosal-irritation test. The tear pharmacokinetic profiles of ciprofloxacin were determined in six healthy volunteers after topical administration of a minitablet and a single eye drop in the lower fornix. The drug concentrations in the tear samples collected were measured by using a validated HPLC METHOD: Each volunteer was asked to give an evaluation of the preparations applied by answering a standard questionnaire. RESULTS: The results of the mucosal-irritation test demonstrated the nonirritating properties of the bioadhesive powder mixtures. The ocular minitablet, applied in the fornix was in general well tolerated by the healthy volunteers. The mean tear concentration of ciprofloxacin was 33.0, 135.2, and 33.7 microg/g at 30, 300, and 480 minutes after application of the minitablet. Mean tear levels of 84.7, 45.6, and 8.4 microg/g were obtained at 5, 30, and 60 minutes after application of an eye drop. CONCLUSIONS: Due to their prolonged drug release properties, the ocular minitablets containing ciprofloxacin can be considered as a promising drug delivery system to be used in the treatment of ulcerative bacterial keratitis.

The evaluation of the local tolerance of vaginal formulations, with or without nonoxynol-9, using the slug mucosal irritation test.

BACKGROUND: Frequent use of some vaginal formulations can induce mucosal irritation. Therefore, it is important to evaluate their vaginal tolerance. GOAL: The goal of this study was to optimize the mucosal irritation test using slugs for the evaluation of the local tolerance of vaginal gels and investigate the relevance of the test. STUDY DESIGN: The irritation potential of the gels was assessed by the amount of mucus produced during a repeated 30-minute contact period. Membrane damage was estimated from the release of proteins and enzymes. After optimization of the procedure, the local tolerance of several vaginal gels was evaluated. RESULTS: Hydroxyethyl cellulose gel induced no irritation, because the mucus production and the protein release were low and no enzyme release was detected. Replens and K-Y jelly resulted in an increased mucus production; however, no increased protein and no enzyme release were detected. The nonoxynol-9-containing gels Protectaid, Advantage S, and Conceptrol caused a higher mucus production and an increased protein release and/or enzyme release, indicating severe irritation. CONCLUSION: The mucosal irritation test using slugs can be used for local tolerance testing of vaginal formulations.