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Related Concept Videos

Drug Absorption Mechanism: Passive Membrane Transport01:23

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Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
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Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
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Passive Diffusion: Overview and Kinetics01:17

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Passive diffusion is a critical process that allows small lipophilic drugs to cross the cell membrane along a concentration gradient. This mechanism's efficiency depends on four primary factors: the membrane's surface area, the drug's lipid-water partition coefficient, the concentration gradient, and the membrane's thickness.
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Methods for Studying Drug Absorption: In vitro01:16

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In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
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Factors Affecting Drug Distribution: Tissue Permeability01:30

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The drug distribution process within the human body is a complex interplay of various physicochemical properties inherent to the drugs. These properties, including molecular size, ionization degree, partition coefficient, and stereochemical nature, significantly impact how drugs permeate biological membranes to reach their target tissues.
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Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport01:23

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Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
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Updated: Jun 23, 2025

A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates
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Simulating the Skin Permeation Process of Ionizable Molecules.

Magnus Lundborg1,2, Christian Wennberg1,3, Erik Lindahl4,5

  • 1SciLifeLab, ERCO Pharma AB, 171 65 Solna, Sweden.

Journal of Chemical Information and Modeling
|June 25, 2024
PubMed
Summary
This summary is machine-generated.

Ionizable drug molecules permeate the skin barrier. While dynamic protonation simulations offer insights, calculations of skin permeability coefficients can rely solely on the neutral form of these molecules.

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Area of Science:

  • Pharmacokinetics
  • Computational Chemistry
  • Materials Science

Background:

  • Ionizable molecules, like drugs, are crucial in pharmaceuticals.
  • The skin barrier presents a significant challenge for drug delivery.
  • Current models often assume passive diffusion of neutral drug species.

Purpose of the Study:

  • To investigate the dynamic protonation behavior of ionizable molecules during skin permeation.
  • To determine if dynamic protonation simulations are necessary for calculating skin permeability coefficients.
  • To compare the permeation of weak acids versus weak bases through lipid bilayers.

Main Methods:

  • Molecular dynamics (MD) simulations were employed.
  • Simulations were conducted separately for charged and neutral states of molecules.
  • Three weak acids and three weak bases were studied across a lipid barrier model.

Main Results:

  • Weak acids showed higher ionization than weak bases in the lipid headgroup region near their pKa.
  • Dynamic protonation simulations provided informative data on molecular behavior.
  • However, these dynamic simulations were not essential for permeability coefficient calculations in the studied cases.

Conclusions:

  • Skin permeability calculations can effectively utilize only the neutral form of ionizable molecules.
  • The assumption of neutral form permeation is sufficient for calculating permeability coefficients.
  • Understanding dynamic protonation is valuable but not always required for quantitative predictions.