Affinity of Lipophilic Drugs to Mixed Lipid Aggregates in Simulated Gastrointestinal Fluids
| Autor: | Panagiota Zarmpi, Jonas H Fagerberg, Hasnaa Jabbar, Nikoletta Fotaki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Absorption (pharmacology)
Drug Ionization food.ingredient media_common.quotation_subject Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Lecithin 03 medical and health sciences 0302 clinical medicine food Lecithins Solubilization Dissolution testing Biorelevant dissolution media Solubility media_common Chromatography Chemistry Mixed lipid aggregates Drug lipophilicity Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Bioavailability Body Fluids Pharmaceutical Preparations Affinity Lipophilicity 0210 nano-technology Drug metabolism |
| Zdroj: | Fagerberg, J H, Zarmpi, P, Jabbar, H & Fotaki, N 2021, ' Affinity of Lipophilic Drugs to Mixed Lipid Aggregates in Simulated Gastrointestinal Fluids ', Journal of Pharmaceutical Sciences, vol. 110, no. 1, pp. 186-197 . https://doi.org/10.1016/j.xphs.2020.09.053 |
| DOI: | 10.1016/j.xphs.2020.09.053 |
| Popis: | Mixed lipid aggregates, comprising of bile salts and phospholipids, present in the small intestine assist in drug solubilization and subsequent drug dissolution and absorption through the intestinal epithelium. The increased variability in their levels, observed physiologically, may create challenges not only for in vivo bioavailability and bioequivalence studies, but also for in vitro bio-predictive studies as correlations between in vitro and in vivo data are not always successful. The current study investigated the impact of biorelevant dissolution media, with physiologically relevant sodium taurocholate and lecithin levels, on the apparent solubility and affinity of lipophilic compounds with a wide range of physicochemical properties (drug ionization, drug lipophilicity, molecular weight) to mixed lipid aggregates. Apparent solubility data in biorelevant dissolution media for the studied neutral drugs, weak bases and weak acids were compared against a phosphate buffer pH 6.5 in the absence of these lipidic components. Presence of mixed lipid aggregates enhanced the apparent solubility of the majority of compounds and the use of multivariate data analysis identified the significant parameters affecting drug affinity to mixed lipid aggregates based on the chemical class of the drug. For neutral drugs, increasing bile salt concentrations and/or drug lipophilicity resulted in greater enhancement in apparent solubility at 24-hr. For weak bases and weak acids, the effect of increasing bile salt levels on apparent solubility depended mostly on an interplay between drug lipophilicity and drug ionization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
https://purehost.bath.ac.uk/ws/files/214916433/Lipophilic_drugs_and_mixed_aggregates_Dr_N_Fotaki.pdf
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