Preparation of mebendazole HP-beta-cyclodextrin complexes using water-soluble polymers and organic acids

Mebendazole (MBZ) is a carbamate derivative with an aminobenzimidazole structure. It possesses antihelminthic properties and is particularly insoluble in water. In order to increase its aqueous solubility, hydroxpropyl-beta-cyclodextrin (HP-beta-CD) was used in combination with water-soluble polymers (polyvinylpyrrolidone or hydroxypropymethyl cellulose) and different organic acids (citric or tartaric). Increased solubility was observed on heating the mixture. The effects of the time and temperature of the heating process on drug solubility and stability were investigated. The results clearly show that the best conditions for increasing solubility and limiting degradation of MBZ is to heat a combination of MBZ, HP-beta-CD (200 mM), tartaric or citric acid (50 mM) and HPMC (0.1% w/v) in a water-bath at 95degreesC for 60 min. This method increases solubility to about 680 mug/ml and limits degradation to 2.5%.