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Related Concept Videos

Bioavailability Enhancement: Drug Permeability Enhancement01:27

Bioavailability Enhancement: Drug Permeability Enhancement

After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt secretion,...
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
Pore Transport and Ion-Pair Transport01:17

Pore Transport and Ion-Pair Transport

Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited  but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Drug Absorption Mechanism: Passive Membrane Transport01:23

Drug Absorption Mechanism: Passive Membrane Transport

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 weak...

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Mitigating permeability-mediated risks in drug discovery.

Jianling Wang1, Suzanne Skolnik

  • 1Novartis Institutes for Biomedical Research, Metabolism and Pharmacokinetics, 250 Massachusetts Avenue, Cambridge, MA 02139, USA. Jianling.wang@novartis.com

Expert Opinion on Drug Metabolism & Toxicology
|January 13, 2010
PubMed
Summary
This summary is machine-generated.

Optimizing drug absorption requires understanding permeability, which is crucial for drug development. This review covers in silico, in vitro, and in vivo methods to assess and improve drug permeability, mitigating risks early in discovery.

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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
18:57

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

Area of Science:

  • Pharmacokinetics and Drug Discovery
  • Biopharmaceutical Sciences

Background:

  • Adequate drug permeability is vital for oral absorption and accurate pharmacokinetic/pharmacological data interpretation.
  • Permeability limitations involve complex mechanisms across multiple organs (gastrointestinal tract, liver, kidney, blood-brain barrier).
  • Pharmaceutical options for enhancing drug permeability are currently limited.

Purpose of the Study:

  • To review comprehensive in silico, in vitro, and in vivo/ex vivo/in situ tools for assessing drug permeability.
  • To address the in vivo predictive impact of in vitro permeability assays.
  • To discuss challenges with difficult-to-drug compounds in drug discovery.

Main Methods:

  • Review of established and emerging methodologies for permeability assessment.
  • Analysis of drug discovery case studies and statistical data from Novartis.
  • Evaluation of the advantages and limitations of various permeability testing tools.

Main Results:

  • An integrated strategy is presented for leveraging permeability assessment tools.
  • The strategy aims to mitigate absorption and safety risks associated with permeability.
  • The approach is applicable across different stages of drug discovery and development.

Conclusions:

  • Utilizing a comprehensive suite of in silico, in vitro, and in vivo tools is critical for early drug discovery.
  • Proactive identification and mitigation of permeability issues are essential.
  • Employing the right tools at the right time ensures effective problem-solving in drug development.