Assessment of the anti-malarial properties of dihydroartemisinin-piperaquine phosphate solid lipid-based tablets.

Abstract

BACKGROUND Artemisinin based combination therapies (ACTs) typified by dihydroartemisinin-piperaquine phosphate is one of the first line drugs used in the treatment of Plasmodium falciparum malaria. However, the emergence of drug resistance to ACTs show the necessity to develop novel sustained release treatment in order to ensure maximum bioavailability. OBJECTIVES To formulate dihydroartemisinin (DHA)-piperaquine phosphate (PQ) sustained release tablets based on solidified reverse micellar solutions (SRMS). METHODS The SRMS was prepared by fusion using varying ratios of Phospholipon® 90H and Softisan® 154 and characterised. The tablets were prepared by using an in-house made and validated mould. The formulations were tested for uniformity of weight, hardness, friability, softening time, erosion time and in vitro-in vivo dissolution rate. Anti malarial properties were studied by modified Peter's 4-days suppressive test in mice. One-way analysis of variance (ANOVA) was used in analysis of results. RESULTS Smooth caplets, with average weight of 1300 ± 0.06 to 1312 ± 0.11 mg, drug content of 61 mg for DHA and t 450 mg for PQ. Tablets hardness ranged from 7.1 to 9.0 Kgf and softening time of 29.50 ± 1.90 min. Erosion time of 62.00 ± 2.58 to 152.00 ± 1.89 min were obtained for tablets formulated with Poloxamer 188 (Batches R2, S2 and T2) which significantly reduced the softening and erosion time (p < 0.05). In vitro release showed that optimized formulation had maximum release at 12 h. Formulations exhibited significantly higher parasitaemia clearance and in vivo absorption compared to marketed formulations at day 7 (p < 0.05). CONCLUSION DHA-PQ tablets based on SRMS is much easier and relatively cheaper to produce than compressed tablets. They also showed exceptionally better treatment of malaria owing to their sustained release properties and improved bioavailability and is recommended to Pharmaceutical companies for further studies.