Preparation, Evaluation and Optimization of Rapidly Disintegrating Tablets of Artemether-Lumefantrine Fixed Dose Combination

Abstract

The purpose of this work was to develop rapidly disintegrating tablet (RDT) of artemether-lumefantrine fixed dose combinations (FDC). RDTs disintegrate either rapidly in water, to form a stabilized suspension, or disperse instantaneously in the mouth to be swallowed without the aid of water. Granules containing artemether, lumefantrine, camphor, crospovidone (CPVP), and Avicel® PH 101 were prepared by wet granulation technique and the granules were air dried overnight. Tablets were first prepared and later exposed to vacuum to sublime the camphor. The tablets were evaluated for percentage friability, wetting time, disintegration time and other characteristics. A 22 full factorial design was used to investigate the combined influence of 2 formulation variables: the amount of camphor and CPVP. At a higher percentage of camphor (10%), the value of friability was above 1%. However, when the composition of camphor was reduced to 5%, the maximum percent friability obtained was 0.685. At a lower level of camphor (5%), an increase in the level of CPVP to 15% resulted in tablets which disintegrated rapidly within 19 sec having a better mechanical resistance (0.51% friability). The optimum formulation disintegrated within 17 sec having percent friability of 0.230. The unit dose content uniformity, dissolution rate, assay values and other tablet characteristics evaluated were all within the acceptable limits. Thus, it was possible to formulate an RDT of artemether-lumefantrine FDC using CPVP as a disintegrant and camphor as a pore forming agent.

Keywords: rapidly disintegrating tablet, crospovidone, artemether-lumefantrine, optimization, fixed dose combinations