Chlorhexidine-containing mucoadhesive polymeric compacts designed for use in the oral cavity:: an examination of their physical properties, in vitro/in vivo drug release properties and clinical acceptability

This study describes the formulation, physicochemical and mucoadhesive properties and in in vitro/in vivo release of chlorhexidine from mucoadhesive, polymeric compacts, designed for application within the oral cavity. Compacts were prepared by direct compression of mixtures containing 100 mg sodium carboxymethylcellulose (NaCMC), 25 mg hydroxyethylcellulose (HEC)/75 mg polyacrylic acid (PAA) and 75 mg HEC/25 mg FAA. The mechanical and mucoadhesive properties of the drug-loaded compacts were examined using a texture analyzer in compression and tension modes, respectively. Evaluation of mucoadhesion was performed using a mucin-coated gauze substrate. In vitro release of chlorhexidine was performed under sink conditions (phosphate buffered saline, pH 7.0, 37degreesC) using a Caleva 7ST dissolution apparatus. Salivary chlorhexidine levels were determined following intra-oral placement of drug-containing formulations. Quantification of the mass of chlorhexidine released both in vitro and in vivo was performed using HPLC with ultraviolet detection. Furthermore, the in vivo acceptability of the various polymeric compacts was assessed in volunteers using standard questionnaires. Compacts composed of HEC/PAA exhibited greater in vivo retention than those composed of NaCMC. Compacts composed of 25 mg FAA and 75 mg HEC displayed greatest patient acceptability. Introduction of chlorhexidine into these compacts did not significantly compromise either the work required for compact fracture or the in vitro mucoadhesion. Controlled release of chlorhexidine from these compacts was observed both in vitro and in vivo, the concentration of chlorhexidine in saliva exceeding the minimum inhibitory concentration of the common oral pathogens over the study period. In light of the patient acceptability and in vivo performance, it is suggested that the compact composed of 25 mg PAA/75 mg HEC containing 10 mg chlorhexidine offers considerable promise for use as an antimicrobial agent in the oral cavity. (C) 2003 Kluwer Academic Publishers.