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Investigation of the molecular level interactions between lipid-based formulations, membranes, and drug molecules
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. (Pharmaceutics and Biopharmaceutics)
2023 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

Oral administration of drugs can be problematic for the active pharmaceutical ingredient (API) with poor solubility in gastric or intestinal fluid, large molecules, non-stable drugs in gastrointestinal tract, and drug candidates that do not follow Lipinski's ‘rule-of-five’. Advanced formulation strategies are required to overcome such problems. Lipid-based formulations (LBF) can play a key role in solubilizing and stability of the drug molecules in the intestine which can subsequently lead to the enhanced absorption of the hydrophobic drugs. However, the limited use of this strategy results from the incomplete understanding of drug solubility in lipid vehicles, and the mechanism behind the performance of different types of LBFs. Therefore, studying how LBFs load the drug molecules in the colloidal structures is important to enhance the transport of challenging drugs to the intestinal epithelium. Furthermore, it is important to understand how the LBF impact increases the bioavailability of drugs. In this work, we established coarse-grained molecular dynamics simulations as a tool to understand how LBFs enhance the transport of challenging drugs to and across the intestinal epithelium. More importantly, it enhances understanding of interactions between excipients and drug molecules at a feasible time, and scale.  We used LBFs type 3A-MC and 3B-MC in their digested and undigested form. we simulate the interactions of LBFs with two APIs, felodipine (FEL) and octreotide (OCT). We also investigated the transfer of the molecules from the LBFs to the intestinal membrane. LBFs were considered in both dispersed and digested states. We simulated a number of systems containing medium-chain lipids with varying proportions of triglycerides, diglycerides, and monoglycerides. Based on these simulations we conclude that the LBFs studied were applicable for felodipine however there are some differences between the two different formulations in digested and undigested form but octreotide does not have any tendency to seat in the colloid. Felodipine seems to be delivered to the membrane by both LBFs. On the contrary, octreotide reaches the membrane regardless of the LBF.  

Place, publisher, year, edition, pages
2023. , p. 28
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-505081OAI: oai:DiVA.org:uu-505081DiVA, id: diva2:1769554
Subject / course
Pharmacy
Educational program
Master's Programme in Pharmaceutical Modelling
Supervisors
Examiners
Available from: 2023-06-19 Created: 2023-06-17 Last updated: 2023-06-19Bibliographically approved

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CiteExportLink to record
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  • apa
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