Sugars as solid dispersion carrier to improve solubility and dissolution of the BCS class II drug: clotrimazole

Abstract

Solid dispersion of poorly soluble BCS class II drug, clotrimazole, was prepared with the aim of enhancing its dissolution profile. Solid dispersions were prepared using various sugars as carriers at different weight ratio to drug-like d-mannitol, d-fructose, d-dextrose and d-maltose by fusion method. The solubility of plain clotrimazole in different percent of sugar solutions was measured. Also, its solubility in solid dispersion and their physical mixture were assessed. The dissolution of all the prepared SD tablets, direct compressed clotrimazole tablet and plain drug were tested using the U.S. Pharmacopeia convention (USP) apparatus II. The dissolution profiles were characterized by parameters like area under curve (AUC), mean residence time (MRT), mean dissolution time (MDT) and percent dissolution efficiency (% DE). The release kinetics study was performed using DD Solver TM software. The selected solid dispersions (SDs) were evaluated for antifungal activity. A 100% solution of mannitol showed 806-fold increases in solubility as compared with plain clotrimazole in water. It was observed that the dissolution profile of clotrimazole was improved by mannitol SD at drug to sugar ration of 1:3. The percent DE value for mannitol SD tablet was found to be 77.3516% as against plain drug and directly compressed tablet of clotrimazole at 50.9439% and 31.33%, respectively. Also the antifungal activity indicated by inhibition zone was found to be 54 mm indicating enhance activity against Candida albicans as compared with plain CTZ at 6.6 mm. Thus, it can be concluded that the sugar alcohol, that is, mannitol is a more promising hydrophilic carrier for solid dispersion preparation to improve the solubility and dissolution of poorly soluble drugs.

• Clotrimazole
• dextrose
• fructose
• maltose
• mannitol
• simulated vaginal fluid
• solid dispersion

Declaration of interest

We have no personal relationship with other people or organization that could inappropriately influence the presented work or any affiliation with any organization with a financial interest, direct or indirect in the subject matter or materials discussed in the manuscript.