The Application of Modified Flow-Through Cell Apparatus for the Assessment of Chlorhexidine Dihydrochloride Release from Lozenges Containing Sorbitol

Abstract

The objective of this work was to apply a new apparatus for the assay of the drug release from lozenge tablet with a potential use in the treatment of oral candidosis and another conditions connected to microbial etiopathology in the oral cavity or as an antiplaque factor. Also, an approach to comparison of the applied method with the classical paddle apparatus method was performed. Tablets containing chlorhexidine dihydrochloride were formulated with granulated sorbitol of different grades (diameter of 110, 180, 480, and 650 microm, respectively), lactose, and magnesium stearate as excipients. Tablets were obtained through direct compression, and uniformity of weight, friability, breaking strength, disintegration, and release rate were evaluated. The disintegration times ranged between 10 and 21 min. In the next stage of the study, the release of chlorhexidine from lozenges prepared with granulated sorbitol grade 110 microm and different amounts of lactose and magnesium stearate was assessed. Two stages were observed during the release of chlorhexidine dihydrochloride from the lozenges, assayed by the classical paddle apparatus method II USP. In the first stage, release rates were between 2.6 x 10(-2) and 4.7 x 10(-2) min(-1), in the second stage between 1.7 x 10(-3) and 7.7 x 10(-3) min(-1). In the case of the in-house method, the release was near to first-order kinetics through the entire release experiment, with rate constants between 3.6 x 10(-2) and 6.6 x 10(-2) min(-1). The sorbitol granulate of granules with diameter 110 microm was found to be most suitable for the lozenges with chlorhexidine dihydrochloride and lactose. The in-house release method, proposed in this work, seems to be more realistic for the preliminary assessment of predicted drug concentrations in the oral cavity after the intake of a lozenge.