In vivo evaluation of the vaginal distribution and retention of a multi-particulate pellet formulation

Non-disintegrating microcrystalline cellulose pellets (MCC) and disintegrating starch-based pellets were evaluated as new vaginal drug delivery forms and compared with a powder formulation. Pellets and powder were packed in a HPMC or hard gelatine capsule and vaginally administered to five series of five healthy volunteers. Distribution and retention of the multi-particulate formulation was monitored by colposcopy and swabbing. Capsule disintegration in the vagina was slow. MCC pellets clustered around the fornix 3 h after administration, and after 24 h only a few pellets were detected in the vaginal cavity. In contrast, starch-based pellets already started to disintegrate 6 h after administration, resulting in a complete coverage of the vaginal mucosa after 24 h in 8 out of 10 volunteers. The powder formulation had a better distribution after 6 h, although after 24 h almost no powder remained in the vagina. These results were confirmed by swabbing to determine the amount of riboflavin sodium phosphate (used as marker) distributed in the different vaginal regions.