Bioavailability Enhancement of Artemether and Lumefantrine by Improving Solubility and Dissolution Rate using Solid Dispersion Technique

Abstract

Artemether-lumefantrine is World Health Organization approved fixed dose combination for malaria treatment. These drugs have poor bioavailability due to low solubility and dissolution. The objective of this work was to improve bioavailability by increasing solubility and dissolution of both drugs. In this work solid dispersion using hydrophilic carriers like polyvinylpyrrolidone K-30, Soluplus and Lutrol F68 by solvent evaporation technique was prepared and evaluated for solubility, flow property, differential scanning calorimetry, x-ray diffraction analysis, scanning electron microscopy, disintegration and dissolution study. The drugs were determined simultaneously by high performance liquid chromatography method using various surfactants in different dissolution media. Solubility of the drugs was increased in all solid dispersions compared to pure drugs. Flow properties of solid dispersions containing polyvinylpyrrolidone K-30 were better than other carriers and the disintegration time of immediate release tablet containing drug and polyvinylpyrrolidone K-30 (1:0.2) was less than other solid dispersions. X-ray diffraction analysis, differential scanning calorimetry and scanning electron microscopy results indicated decrease in crystalline nature of drugs and their dissolution rate was enhanced than plain drugs and marketed formulations in acidic buffer containing myrj 52 (1 %) as dissolution medium. The pharmacokinetic studies in mice revealed that artemether-lumefantrine solid dispersion immediate release tablet had higher area under the curve, maximum plasma concentration for artemether and lumefantrine than plain and marketed tablet. Thus this technique successfully improved solubility, dissolution rate and hence the bioavailability of artemether and lumefantrine which was determined by single dissolution method.