Mesoporous Silica Carrier-Based Composites for Taste-Masking of Bitter Drug: Fabrication and Palatability Evaluation.

Palatability is one of the most critical characteristics of oral preparations. Therefore, the exploration of new techniques to mask the aversive taste of drugs is in continuous demand. In this study, we fabricated and characterized composites based on mesoporous silica (MPS) that consisted of MPS, a bitter drug, and release regulators. We conducted a palatability evaluation to assess the taste-masking efficacy of the composites. The composites were prepared using the dry impregnation method combined with hot-melt extrusion. Morphology and components distribution in composites were characterized by scanning electron microscopy, confocal laser scanning microscopy, X-ray photoelectron spectroscopy, powder flow properties evaluation, and nitrogen-sorption measurement. The results demonstrated that drugs mainly existed in the inner pore of composites, and release regulators existed in the inner pore and covered the composites' surface. Interactions among the composite components were studied using powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The drug loaded into the composites was amorphous, and an intermolecular interaction occurred between the drug and the MPS. Taste-masked composites significantly reduced drug release levels under mouth conditions; thus, they prevented the interaction of the dissolved drug with taste receptors and improved palatability. An electronic tongue evaluation and a human taste panel assessment confirmed the better palatability of taste-masked composites. Moreover, the desired drug release behavior can be adjusted by choosing an appropriate release regulator, with stronger hydrophobicity of release regulators resulting in slower drug release. This work has provided new insights into taste-masking strategies for drugs with unpleasant tastes.

Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by 1H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p < 0.01), which was comparable to verapamil coperfusion effect. Similarly, CsA + CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.