| Autor: |
Narazaki R; College of Pharmacy, The University of Arizona, Tucson, Arizon 85721-0207, USA. r-narazaki@hhc.eisai.co.jp, Sanghvi R, Yalkowsky SH |
| Jazyk: |
angličtina |
| Zdroj: |
Chemical & pharmaceutical bulletin [Chem Pharm Bull (Tokyo)] 2007 Aug; Vol. 55 (8), pp. 1203-6. |
| DOI: |
10.1248/cpb.55.1203 |
| Abstrakt: |
This manuscript is a study of precipitation of insoluble drug upon dilution from the pH-cosolvent solubilized formulation with simulated blood fluid. An equation is developed to estimate drug precipitation upon dilution of combined pH-cosolvent solubilized formulations. This is an extension of a previous equation used for the estimation of drug precipitation from simple pH controlled formulations. The proposed equation considers the effect of the cosolvent and its concentration on the pK(a) of the drug as well as all buffering species. According to the proposed equation and our experimental data, the addition of cosolvent on the pH solubilized formulation could increase total drug solubility in the formulation. However, the solubility after dilution became lower than the 0% ethanol formulation because of the change in both drug and buffer pK(a) values. Since this equation is based on the equilibrium condition, it is the worst case scenario for precipitation. This equation provides useful information regarding the feasibility of the successful use of pH-cosolvent combinations in drug formulation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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