SOLUBILITY, DISSOLUTION TEST AND ANTIMALARIAL ACTIVITY OF ARTESUNATE NICOTINAMIDE CO CRYSTAL PREPARED BY SOLVENT EVAPORATION AND SLURRY METHODS

摘要

Objective: The aims of this study was to investigate the solubility, dissolution rate and antimalarial activity against Plasmodium berghei of artesunate (AR)-nicotinamide co-crystal prepared by solvent evaporation (CoSE) and slurry (CoS) method. Methods: Co-crystals of AR-nicotinamide prepared by solvent evaporation and slurry methods were tested for solubility, dissolution rate and activity of antimalarial compared to pure AR and physical mixture (PM) of AR and nicotinamide. Solubility test was conducted in distilled water at 37±0.5°C and dissolution test was done in distilled water medium at 37±0.5°C using paddle stirrer. Antimalarial activity test was carried out on female mice infected by P. berghei then parasitemia was observed. Results: The AR solubility of slightly increased from 1236.66±141.42 to 1368.46±49.17 mg/L. Dissolution data at 30 minutes respectively for AR, PM, CoS and CoSE (76.51±14.93; 75.45±18.07; 85.14±12.94 and 123.24±7.68%). The results were antimalarial activity test of P. berghei showed that percent inhibition 84.98-89.50%. These data showed no significant differences in antimalarial activity between AR, CoS and CoSE. Conclusions: Co-crystal AR nicotinamide prepared by solvent evaporation and slurry methods could increase the dissolution rate of AR in distilled water medium compared to pure AR. Co-crystal AR nicotinamide prepared by solvent evaporation was not significant difference as antimalarial activity in P. berghei compared to pure AR.