Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis

Abstract

The method based on integrating the principles of solid dispersion and nanocrystal techniques was developed to prepare polymer crystals (PCs) of mebendazole (MBZ) and polyethylene glycol (PEG). Powder X-Ray diffraction (PXRD) of the PC crystals shows the required integrated crystalline and amorphous regions. The in vitro solubility studies showed a 32-fold increase in the solubility of the drug. Tests of dissolution of the PCs showed that the crystals have an enhanced dissolution rate in comparison to those in the MF. The results of the pharmacokinetic study showed a 2.12-fold increase in the bioavailability of the drug. Thus, the present study has proved the potential in enhancing solubility, dissolution, and bioavailability of the drug.

N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs

“…MBZ’s low solubility is hypothesized to be due, at least in part, to its planar structure causing strong stacking interactions in the crystal lattice, which are reinforced by intermolecular hydrogen bonds . Previous studies have attempted to increase MBZ’s bioavailability using oil-based formulations, nanoformulations, , and prodrug strategies, , although with varied success. Our work extends and improves upon prior MBZ prodrug efforts by exploring alternative N-linked substituents including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl promoieties.…”

Application of Box–Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles

“…Th ese nanosystems can advantageously improve the therapeutic effi cacy of a drug by enhancing its bioavailability (Mohammadi et al 2011, Adibkia et al 2012, Chaudhary et al 2015 and serum stability (Bowman and Leong 2006).…”

Effect of Shape on Mesoporous Silica Nanoparticles for Oral Delivery of Indomethacin

“…However, there are still limitations to this form of delivery, and the challenge remains to improve oral bioavailability of Biopharmaceutical Classification System (BCS) II molecules, owing to their low solubility and poor stability in the gastrointestinal tract (GI tract). In recent years, many strategies have been proposed to improve the dissolution and bioavailability of poorly water-soluble drugs, including spray drying [4,5,6], solid dispersions [7,8,9], nanosuspensions [10,11], cryogenic technologies [12,13], and prodrug approaches [14]. For example, Xu et al prepared hydrophilic polymer-based solid dispersions by a freeze-drying technique, and enhanced the dissolution rate and oral bioavailability of valsartan [15].…”