MELT GRANULATION OF SOME ANTI-MALARIAL FORMULATIONS

Abstract

Artesunate is used as a drug of choice in treatment of uncomplicated cases of malaria due to Plasmodium falciparum strains that are highly drug-resistant, it is a poorly water soluble drug and liable to aqueous hydrolysis. Melt granulation is a good technique instead of traditional wet granulation technique to produce more stable as well as more bioavailable immediate release Artesunate tablets. This study aims to formulate Artesunate as an immediate release tablet through optimization of melt granulation technique to improve the dissolution of the drug. Three different meltable binders were used (Polyethylene Glycol PEG 6000, Poloxamer 188 and Gelucire 50/13) for granulation step in high shear mixer prior tablets compression step applying Box-Behnken experimental design to determine the significant variables and their interactions that impact dissolution of Artesunate. Optimization mathematical models showed that by increasing binder concentration, the particle size below which 50% of particles exist was increased, and narrow particle size distribution with minimum fines percentage was produced. Higher binder concentration and impeller speed resulted in significant retardation of tablets dissolution (p<0.05). PEG 6000 and Poloxamer 188 based tablets showed faster disintegration and dissolution than both Gelucire 50/13 based tablets, and tablets prepared by wet granulation due to hydrophilic pore forming. Stability results of assay and dissolution tests supported the preference of Poloxamer 188 over PEG 6000 as the meltable binders of choice to enhance Artesunate dissolution from immediate release tablets. Melt granulation was better than the traditional wet granulation in tailoring drug delivery for a robust drug product.