Suitability of Artificial Membranes in Lipolysis-Permeation Assays of Oral Lipid-Based Formulations

Autor: Christel A. S. Bergström, Oliver J. Hedge
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Swine
Synthetic membrane
Pharmaceutical Science
Administration
Oral
lipid-based formulation
02 engineering and technology
digestion
030226 pharmacology & pharmacy
Lecithin
Pharmaceutical Sciences
0302 clinical medicine
Fenofibrate
Lecithins
Pharmacology (medical)
Drug Carriers
Chemistry
Permeation
021001 nanoscience & nanotechnology
self-emulsifying oral drug-delivery systems
Lipids
Membrane
Molecular Medicine
Biological Assay
permeation
0210 nano-technology
Biotechnology
Research Paper
food.ingredient
Drug Compounding
Lipolysis
Absorption (skin)
Models
Biological
Permeability
artificial membrane
Excipients
03 medical and health sciences
food
In vivo
Alkanes
Animals
Humans
Pharmacology
Chromatography
Organic Chemistry
Membranes
Artificial
Farmaceutiska vetenskaper
In vitro
Drug Liberation
Solubility
Pancreatin
Adsorption
Caco-2 Cells
Zdroj: Pharmaceutical Research
Popis: Purpose To evaluate the performance of artificial membranes in in vitro lipolysis-permeation assays useful for absorption studies of drugs loaded in lipid-based formulations (LBFs). Methods Polycarbonate as well as PVDF filters were treated with hexadecane, or lecithin in n-dodecane solution (LiDo) to form artificial membranes. They were thereafter used as absorption membranes separating two compartments mimicking the luminal and serosal side of the intestine in vitro. Membranes were subjected to dispersions of an LBF that had been digested by porcine pancreatin and spiked with the membrane integrity marker Lucifer Yellow (LY). Three fenofibrate-loaded LBFs were used to explore the in vivo relevance of the assay. Results Of the explored artificial membranes, only LiDo applied to PVDF was compatible with lipolysis by porcine pancreatin. Formulation ranking based on mass transfer in the LiDo model exposed was the same as drug release in single-compartment lipolysis. Ranking based on observed apparent permeability coefficients of fenofibrate with different LBFs were the same as those obtained in a cell-based model. Conclusions The LiDo membrane was able to withstand lipolysis for a sufficient assay period. However, the assay with porcine pancreatin as digestive agent did not predict the in vivo ranking of the assayed formulations better than existing methods. Comparison with a Caco-2 based assay method nonetheless indicates that the in vitro in vivo relationship of this cell-free model could be improved with alternative digestive agents.
Databáze: OpenAIRE
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