Enteric complex layer-coated controlled release of capsaicin from phytosterol/γ-cyclodextrin microparticles via guest exchange reaction with taurocholic acid

• Published in: European journal of pharmaceutical sciences 2022-01, Vol.168, p.106038-106038, Article 106038
• Main Authors: Sasako, Hiroshi, Koyama, Kazuo, Higashi, Kenjirou, Ueda, Keisuke, Ishimoto, Arisa, Moribe, Kunikazu
• Format: Article
• Language: English
• Subjects: Capsaicin; Cyclodextrin; Delayed-Action Preparations; Enteric release; gamma-Cyclodextrins; Guest exchange; Phytosterols; Solubility; Taste masking; Taurocholate; Taurocholic Acid
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2021.106038

Phytosterol (PSE)/γ-cyclodextrin (γ-CD) microparticles have a capsule-like structure, wherein the hydrophobic PSE core is surrounded by outer layers of the hydrophilic PSE/γ-CD inclusion complex crystal. The microparticles could mask the undesirable taste of capsaicin (CAP) by encapsulation of CAP into the microparticles. In the present study, the dissolution of CAP from PSE/γ-CD microparticles into artificial intestinal fluids was examined using the paddle method. The dissolution of CAP from the microparticles was suppressed at pH 1.2 and 5.0. On the other hand, the dissolution was significantly enhanced in fasted and fed state simulated intestinal fluid (FaSSIF and FeSSIF) . Taurocholate (TCA), contained in these artificial fluids, induced rapid dissolution of CAP from microparticles. The mechanism of CAP dissolution from the microparticles in the presence of TCA was investigated using in situ1H NMR spectroscopy. During the incubation of the mixed suspension of the microparticles and TCA, γ-CD peaks started to appear, and the TCA peak showed a gradual upfield shift. Quantitative analysis of NMR results showed that the TCA/γ-CD inclusion complex could form during incubation, according to the dissolution of γ-CD from the microparticles via the guest exchange reaction of PSE by TCA. The collapse of the PSE/γ-CD inclusion complex crystal at the outer shell of microparticles could trigger the release of CAP into the intestinal fluid. Thus, PSE/γ-CD microparticles can be used as an enteric controlled-release system that releases encapsulated drugs not via the conventional pH changes but via guest exchange reaction with TCA. [Display omitted]