Resumé
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | International Journal of Pharmaceutics |
| Vol/bind | 531 |
| Udgave nummer | 2 |
| Sider (fra-til) | 504-511 |
| Antal sider | 8 |
| ISSN | 0378-5173 |
| DOI | |
| Status | Udgivet - 2017 |
Emneord
- Binding constant
- Calorimetry
- Cyclodextrin
- Hydrocortisone
- Inclusion complex
- Phase-solubility
Citer dette
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Soluble 1:1 Complexes and Insoluble 3:2 Complexes : Understanding the Phase-Solubility Diagram of Hydrocortisone and γ-Cyclodextrin. / Schönbeck, Jens Christian Sidney; Madsen, Tobias Løvgren; Peters, Günther H.; Holm, René; Loftsson, Thorsteinn.
I: International Journal of Pharmaceutics, Bind 531, Nr. 2, 2017, s. 504-511.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
TY - JOUR
T1 - Soluble 1:1 Complexes and Insoluble 3:2 Complexes
T2 - Understanding the Phase-Solubility Diagram of Hydrocortisone and γ-Cyclodextrin
AU - Schönbeck, Jens Christian Sidney
AU - Madsen, Tobias Løvgren
AU - Peters, Günther H.
AU - Holm, René
AU - Loftsson, Thorsteinn
PY - 2017
Y1 - 2017
N2 - The molecular mechanisms underlying the drug-solubilizing properties of γ-cyclodextrin were explored using hydrocortisone as a model drug. The BS-type phase-solubility diagram of hydrocortisone with γ-cyclodextrin was thoroughly characterized by measuring the concentrations of hydrocortisone and γ-cyclodextrin in solution and the solid phase. The drug-solubilizer interaction was also studied by isothermal titration calorimetry from which a precise value of the 1:1 binding constant (K11=4.01mM-1 at 20°C) was obtained. The formation of water-soluble 1:1 complexes is responsible for the initial increase in hydrocortisone solubility while the precipitation of entities with a 3:2 ratio of γ-cyclodextrin:hydrocortisone is responsible for the plateau and the ensuing strong decrease in solubility once all solid hydrocortisone is used up. The complete phase-solubility diagram is well accounted for by a model employing the 1:1 binding constant and the solubility product of the precipitating 3:2 entity (K32S=5.51 mM5). For such systems, a small surplus of γ-cyclodextrin above the optimum concentration may result in a significant decrease in drug solubility, and the implications for drug formulations are briefly discussed.
AB - The molecular mechanisms underlying the drug-solubilizing properties of γ-cyclodextrin were explored using hydrocortisone as a model drug. The BS-type phase-solubility diagram of hydrocortisone with γ-cyclodextrin was thoroughly characterized by measuring the concentrations of hydrocortisone and γ-cyclodextrin in solution and the solid phase. The drug-solubilizer interaction was also studied by isothermal titration calorimetry from which a precise value of the 1:1 binding constant (K11=4.01mM-1 at 20°C) was obtained. The formation of water-soluble 1:1 complexes is responsible for the initial increase in hydrocortisone solubility while the precipitation of entities with a 3:2 ratio of γ-cyclodextrin:hydrocortisone is responsible for the plateau and the ensuing strong decrease in solubility once all solid hydrocortisone is used up. The complete phase-solubility diagram is well accounted for by a model employing the 1:1 binding constant and the solubility product of the precipitating 3:2 entity (K32S=5.51 mM5). For such systems, a small surplus of γ-cyclodextrin above the optimum concentration may result in a significant decrease in drug solubility, and the implications for drug formulations are briefly discussed.
KW - Binding constant
KW - Calorimetry
KW - Cyclodextrin
KW - Hydrocortisone
KW - Inclusion complex
KW - Phase-solubility
KW - Binding constant
KW - Calorimetry
KW - Cyclodextrin
KW - Hydrocortisone
KW - Inclusion complex
KW - Phase-solubility
U2 - 10.1016/j.ijpharm.2017.05.024
DO - 10.1016/j.ijpharm.2017.05.024
M3 - Journal article
VL - 531
SP - 504
EP - 511
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 2
ER -