Stabilization of the Metastable α-Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-β-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute)
| Autor: | Yohsuke Shimada, Satoru Goto, Risa Ichii, Yuta Otsuka, Momoko Fujita, Ryosuke Hiroshige, Shota Shimizu, Chihiro Tsunoda, Ayako Wada-Hirai, Ying Peng Li |
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| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Supersaturation Cyclodextrin Calorimetry Differential Scanning Indomethacin beta-Cyclodextrins Analytical chemistry Pharmaceutical Science Amorphous solid 2-Hydroxypropyl-beta-cyclodextrin Differential scanning calorimetry chemistry Solubility Dissolution Powder diffraction Stoichiometry |
| Zdroj: | Journal of pharmaceutical sciences. 110(11) |
| ISSN: | 1520-6017 |
| Popis: | The purpose of this study is to find that a small amount of 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) can produce a parachute effect on indomethacin (INM). From the examination of dissolution curves and concentration after several days, the supersaturation of INM was observed for the mixtures containing HP-β-CD at a molar ratio ≤ 0.5, and the sustained deployment of supersaturation was found not only in equimolar mixtures but also in mixtures with a shortage of HP-β-CD. In the solid state, it was compared the physical properties of INM/HP-β-CD mixtures using two different mixing methods and determined the stoichiometry of INM and HP-β-CD. Differential scanning calorimetry (DSC) revealed that the polymorphs of INM were converted by HP-β-CD into an amorphous state. Furthermore, X-ray powder diffraction (XRPD) and DSC–XRPD demonstrated that INM crystals from the INM/HP-β-CD mixture prepared from an EtOH solution were metastable. In conclusion, these phenomena may be considered the "spring" and "parachute" effects of mixtures with a shortage of HP-β-CD, as they depended on the presence of the metastable α-form of INM. The addition of 1/3 to 1/20 equivalents of HP-β-CD to INM enhanced INM solubility. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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