Effect of squalane on mebendazole-loaded Compritol^®nanoparticles

Abstract

The objective of this study is to develop nanostructured lipid formulations (NLF) of Compritol for the delivery of mebendazole. The formulations were prepared with Compritol 888 ATO, squalane, and Pluronic F68. Nine batches with different amounts of modifier, squalane, and drug were prepared. The formulations were characterized by evaluating particle size, morphology, and zeta potential. The thermal properties of the formulations were analyzed by differential scanning calorimetry (DSC). The encapsulation efficiency of each formulation and the drug release rates from each formulation were quantified by UPLC. The particles were spherical and had median particle sizes between 300 and 600 nm (50th percentile). A linear relationship was observed between Compritol/squalane composition and the melting point of the mixture. The DSC scans of the formulations revealed some recrystallization of the drug from the formulations, and the amount of recrystallization correlated with the amount of squalane in the formulation. Approximately 70% efficiency of encapsulation was observed in the formulations with 30% (w/w) squalane, and these formulations also had faster dissolution rates compared to the other formulations. Overall, the formulations with 30% squalane are the preferred formulation for future testing.

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.…”