Novel cellulose-based amorphous solid dispersions enhance quercetin solution concentrations in vitro

Abstract

Quercetin (Q) is a bioactive flavonol with potential to benefit human health. However, Q bioavailability is relatively low, due to its poor aqueous solubility and extensive phase-II metabolism. Strategies to increase solution concentrations in the small intestinal lumen have the potential to substantially increase Q bioavailability, and by extension, efficacy. We aimed to achieve this by incorporating Q into amorphous solid dispersions (ASDs) with cellulose derivatives. Q was dispersed in matrices of cellulose esters including 6-carboxycellulose acetate butyrate (CCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate suberate (CASub) to afford ASDs that provided stability against crystallization, and pH-triggered release. Blends of CASub and CCAB with the hydrophilic polyvinylpyrrolidone (PVP) further enhanced dissolution. The ASD 10% Q:20% PVP:70% CASub most significantly enhanced Q solution concentration under intestinal pH conditions, increasing area under the concentration/time curve (AUC) 18-fold compared to Q alone. This novel ASD method promises to enhance Q bioavailability in vivo.

Recent trends and applications of polysaccharides for microencapsulation of probiotics

“…One of the most important characters of CAP is that it can function as an enteric coating because of the presence of ionizable phthalate groups. Its solubility depends on the pH of the media, which is insoluble in acid media (pH ≤ 5) but is soluble when the pH is ≥6 (Gilley et al., 2017). In this sense, CAP is able to protect encapsulated core material against the gastric acid in stomach and gradually release the core material in the slightly neutral to alkaline conditions in the intestines.…”

Hydroxypropyl‐β‐cyclodextrin hybrid nanogels as nano‐drug delivery carriers to enhance the solubility of dexibuprofen: Characterization, in vitro release, and acute oral toxicity studies

“…Conventional HPβCD significantly enhanced solubilization efficiency as compared to pure dexibuprofen in all solutions. [32][33][34] Formerly, significantly improved solubilization efficiency of paclitaxel was demonstrated by nanoparticles of star polymer of βCD-poly(N-isopropylacrylamide) by forming supramolecular inclusion complexes. It was suggested that hybrid nanogels facilitated inclusion ability of HPβCD.…”

Amorphous solid dispersions of enzalutamide and novel polysaccharide derivatives: investigation of relationships between polymer structure and performance

“…However, this small group of polymers is not sufficiently structurally diverse to enable systematic study of structure activity relationships, and these polymers were not specifically designed for ASD formulation, but rather were repurposed from other pharmaceutical applications. In recent years, synthesis of novel polymers specifically designed for use in ASDs, as well as to facilitate mechanistic understanding of key polymer functionality, has led to an increase in polymer diversity 11 , 15 . Ultimately, if polymers with enhanced properties can be identified, this may permit a higher proportion of poorly soluble drug candidates to be successfully formulated as ASDs.…”

“…While the Taylor and Edgar groups have described design and in vitro testing of a number of new polysaccharide derivatives for ASDs of poorly soluble drugs 9 , 11 , 15 , 24 , 25 , no in vivo studies have been performed on formulations containing these polymers. The goal of this study was to evaluate in vivo absorption performance of two of these new polymers, selected from a larger group which were first evaluated in terms of their ability to inhibit crystallization during in vitro studies.…”