Investigation of drug partition kinetics to fat in simulated fed state gastric conditions based on drug properties.

Baxevanis, Fotios; Zarmpi, Panagiota; Kuiper, Jesse; Fotaki, Nikoletta

doi:10.1016/j.ejps.2020.105263

Cited by 5 publications

(2 citation statements)

References 76 publications

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“…The feature MoKa.LogD7.4 represents the lipophilicity of the drug, the third most important feature in task two. Positive food effects are associated with drug lipophilicity by lipid emulsification and an increase in luminal solubilisation (Baxevanis et al, 2020;Porter et al, 2008). Abiraterone, for example, shows a dramatic positive food effect depending on the lipidic content of the meal (Schultz et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Machine learning predicts the effect of food on orally administered medicines

Gavins

Elbadawi

et al. 2022

International Journal of Pharmaceutics

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Section: Discussionmentioning

confidence: 99%

Machine learning predicts the effect of food on orally administered medicines

Gavins

Elbadawi

et al. 2022

International Journal of Pharmaceutics

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“…Surprisingly, the model indicates that neutral drugs of higher MW will, as well, be greatly solubilized in the lipid aggregates. Although this finding tackles fundamentals aspects, as larger compounds are not expected to be adequately solubilized, 38 it should be noted that the studied neutral drugs comprised of average molecular weight (MW z 300e400) and that this conclusion should not be extrapolated to larger molecules (MW > 400e500). Increasing the levels of mixed lipid aggregates in the medium will significantly increase the solubility of neutral compounds, as indicated by the significance of the variable BS.…”

Section: Multivariate Data Analysismentioning

confidence: 91%

Affinity of Lipophilic Drugs to Mixed Lipid Aggregates in Simulated Gastrointestinal Fluids

Fagerberg¹,

Zarmpi²,

Jabbar

et al. 2021

Journal of Pharmaceutical Sciences

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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.

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