Cortisone and cortisol break hydrogen-bonding rules to make a drug–prodrug solid solution
| Autor: | Luis Padrela, Simone Bordignon, Kevin M. Ryan, Michele R. Chierotti, Vivek Verma, Monica Lestari, Kieran Lyons, Matteo Lusi |
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| Přispěvatelé: | SFI, EI |
| Rok vydání: | 2020 |
| Předmět: |
formulations
multidrug formulations 010402 general chemistry 01 natural sciences Biochemistry Phase (matter) mixed crystals assisted spray drying General Materials Science hydrocortisone lcsh:Science Dissolution pharmaceutical solids 010405 organic chemistry Chemistry Hydrogen bond cortisone solid solutions mixed crystals multidrug formulations steroids pharmaceutical solids assisted spray drying hydrogen bonding hydrocortisone cortisone General Chemistry Prodrug hydrogen bonding Condensed Matter Physics Research Papers Combinatorial chemistry Supercritical fluid 0104 chemical sciences solid solutions Spray drying lcsh:Q Stoichiometry steroids Solid solution |
| Zdroj: | IUCrJ IUCrJ, Vol 7, Iss 6, Pp 1124-1130 (2020) |
| ISSN: | 2052-2525 |
| DOI: | 10.1107/s2052252520013263 |
| Popis: | In order to form a solid solution with its prodrug cortisone, hydrocortisone (cortisol) must violate Etter’s rule of hydrogen bonding. The preparation of a uniform product with the desired composition, which is hindered under a thermodynamic regime, can be achieved by supercritical assisted spray drying. The new phase enables fine-tuning of the phase’s composition as well as a higher dissolution rate for hydrocortisone. Multidrug products enable more effective therapies and simpler administration regimens, provided that a stable formulation is prepared, with the desired composition. In this view, solid solutions have the advantage of combining the stability of a single crystalline phase with the potential of stoichiometry variation of a mixture. Here a drug–prodrug solid solution of cortisone and cortisol (hydrocortisone) is described. Despite the structural differences of the two components, the new phase is obtained both from solution and by supercritical CO2 assisted spray drying. In particular, to enter the solid solution, hydrocortisone must violate Etter’s rules for hydrogen bonding. As a result, its dissolution rate is almost doubled. |
| Databáze: | OpenAIRE |
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