Dissolution media simulating the intralumenal composition of the small intestine: physiological issues and practical aspects
| Autor: | Nikoletta Fotaki, Christos Reppas, Eleftheria Nicolaides, Maria Vertzoni, Erika Stippler, Christian Leuner, Edmund Kostewicz, Jennifer B. Dressman |
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| Rok vydání: | 2004 |
| Předmět: |
Taurocholic Acid
Eggs Sodium Pharmaceutical Science chemistry.chemical_element Buffers chemistry.chemical_compound Phosphatidylcholine Intestine Small medicine Bile Dissolution testing Solubility Dissolution Pharmacology Chromatography Hydrolysis Osmolar Concentration Solubility equilibrium Small intestine medicine.anatomical_structure Pharmaceutical Preparations chemistry Phosphatidylcholines Salting out Soybeans |
| Zdroj: | Journal of Pharmacy and Pharmacology. 56:453-462 |
| ISSN: | 2042-7158 0022-3573 |
| Popis: | The objective of this study was to test various aspects of dissolution media simulating the intralumenal composition of the small intestine, including the suitability of the osmolality-adjusting agents and of the buffers, the substitution of crude sodium taurocholate (from ox bile) for pure sodium taurocholate and the substitution of partially hydrolysed soybean phosphatidylcholine for egg phosphatidylcholine. It was concluded that biorelevant media should contain sodium as the major cation species to better reflect the physiology. However, the use of non-physiologically relevant buffers is inevitable, especially for simulation of the fed state in the small intestine. The buffers used may affect the solubility product of weakly basic compounds with pKa(s) higher than about 5, the solubility of extremely highly lipophilic compounds due to salting in/out properties of the anion of the buffer and the stability of the dissolving compound. It is prudent in relevant situations to run an additional dissolution test in a modified fed state simulated intestinal fluid (FeSSIF) (or fasted state simulated intestinal fluid (FaSSIF), where applicable) containing alternative buffer species. Although a mixture of bile salts is physiologically more relevant than pure sodium taurocholate, this issue seems to be of practical importance in only a few cases. Adequate simulations in these cases will probably require the use of a number of pure substances and could substantially increase the cost of the test. Finally, unless the drug is extremely lipophilic (ca. logP > 5), egg phosphatidylcholine can be substituted by partially hydrolysed soybean phosphatidylcholine. |
| Databáze: | OpenAIRE |
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