Formulation of a solid intravaginal matrix system to prolong the pH-decreasing effect of lactic acid

Abstract

The aim of our work was to study the applicability of solid matrix systems for the formulation of long-acting intravaginal tablets containing lactic acid. These systems were compressed from matrix granules containing hydroxypropylmethyl cellulose (HPMC), lactose monohydrate and microcrystalline cellulose (MCC, the binder and carrier of lactic acid) as additives. The active pharmaceutical ingredient (API) was incorporated into the granulating fluid and the effect of its concentration (evaluated up to 15%) on the pH-decreasing effect of the tablets was assessed. The particle size and mechanical properties of the granules did not change relevantly. The dissolution of the active component (change in H + concentration) was tested with a modified dissolution test for 8 h. The pH-decreasing effect of tablets was influenced by the lactic acid content. It was the highest for samples containing the largest amount of lactic acid. The cumulative concentration of dissolved H + was plotted, which curve exhibited a break at about 4 h. Up to this time, the shape of the tablets constantly changed (a hemisphere was formed) at every sample, after this time no change in shape could be detected. It can be concluded that in the first stage of dissolution erosion was the main factor influencing the liberation of the API. This is necessary for the detachment of lactic acid from the insoluble MCC. A relatively quick liberation was detected in the initial period (0–4 h) for the samples containing a small amount of lactic acid, which can be explained by the simpler liberation of API. Below 9% lactic acid, the readier liberating sites of the carrier were saturated. In the later stage of dissolution (5–8 h), the slower processes were more relevant. Additionally, it can be stated that the composition applied was appropriate for the formulation of a long-acting matrix system containing lactic acid.