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Enhancement Of Dissolution And Bioavailability Of Mebendazole For The Effective And Safe Management Of Human Echinococcosis

Author(s): R Kalaiselvan, G.S Prasad, P.R Naik, R Manavalan

Mebendazole and β-cyclodextrin molecular inclusion complexes and mebendazole solid dispersions with polyethylene glycol 6000 were prepared by solvent method in different mixing ratios to increase the rate and extent of dissolution and absorption of mebendazole for an effective chemotherapy of human echinococcosis. The enhancement of dissolution of mebendazole was dependent on the carriers used and the nature of presentation of mebendazole in the carriers (physical mixturelsolid dispersion/molecular inclusion). The differential scanning calorimetry indicated the solid inclusion complex formation of mebendazole and β-cyclodextrin at 1:2 molar ratio and mebendazole-polyethylene glycol solid dispersion at 1:4 weight ratio. Stability study reported a significant decline in the potency of mebendazole in all mebendazole-polyethylene glycol solid dispersions. Dissolution rate and dissolution efficiency of mebendazole were improved by both molecular inclusion complexes and solid dispersions of all mixing ratios than the corresponding physical mixtures and pure drug, 1:2 mebendazole-βcyclodextrin showing the highest dissolution among all the preparations. As mebendazole has been reported to undergo extensive first pass metabolism, also a single dose plasma level bioavailability study in rabbits was conducted to confirm the bioavailability performance of mebendazole from the 1:2 mebendazole-βcyclodextrin complex. In the study, not only a statistically significant (p<0.05), but also a great improvement in bioavailability of mebendazole was achieved with 1:2 mebendazole-βcyclodextrin complex as compared to its physical mixture. Bioequivalency study was also performed for 1:0.5 mebendazole- bcyclodextrin complex and 1:4 mebendazole-polyethylene glycol solid dispersion (which were equivalent to each other in dissolution behavior) and this study showed a result opposite to what was expected on the basis of their in vitro drug release profiles. The reported risks in the use of cyclodextrins and the observed stability problem associated with mebendazole-polyethylene glycol solid dispersions were considered in deciding a choice for the treatment of human echinococcosis.


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