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Related Concept Videos

Protein-Drug Binding: Determination Methods01:22

Protein-Drug Binding: Determination Methods

Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
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In Vitro Drug Dissolution: Compendial Testing Models II

Various dissolution methods are utilized to assess a drug’s dissolution rate, including the flow-through cell, paddle-over-disk, cylinder, and reciprocating disk methods.The flow-through cell apparatus (USP (United States Pharmacopeia) method 4) comprises a reservoir for the dissolution medium and a pump that propels the medium through the cell containing the test sample. This method is crucial for assessing modified-release dosage forms with minimally soluble active ingredients, maintaining...
Drug Dissolution: Requirements and Profile Comparison01:14

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The acceptance criteria for dissolution profile data are anchored in Q values, representing the percentage of drug dissolved within a specified period. This assessment unfolds in three stages:First Stage: The test passes if all six drug dosage units are equal to or greater than Q plus 5%; otherwise, the sample proceeds to the second stage.Second Stage: The average of twelve units must be equal to or greater than Q, with no unit falling below Q - 15% to pass; if not, it progresses to the final...
Analyte Adsorption and Distribution01:09

Analyte Adsorption and Distribution

In certain chromatographic separations, solutes transfer between the mobile phase and the stationary phase via sorption, which typically refers to the process of adsorption. For many chromatographic systems, the sorption process often depends on the polarity of the compounds—an expression of the overall dipole moment within the molecule. During the separation process, there is competition between the solute and solvent for adsorption to the stationary phase. Highly polar compounds and solvents...
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Drug Distribution: Volume of Distribution

The volume of distribution refers to the theoretical volume necessary to contain the entire amount of an administered drug at the same concentration observed in the blood plasma. The body's intracellular fluid compartment, which makes up two-thirds of the total body water, is contrasted with the extracellular fluid compartment—comprising plasma and interstitial fluid—that accounts for one-third. The volume of distribution can vary depending on the characteristics of the drug.
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A loading dose is an essential pharmacological strategy to rapidly achieve the target plasma drug concentration necessary for an immediate therapeutic effect. This approach is especially critical for drugs characterized by slow absorption or extended half-lives, where delaying therapeutic plasma levels could compromise treatment outcomes. By administering a loading dose, clinicians ensure a prompt onset of drug action, even for agents with complex pharmacokinetic profiles.Achieving steady-state...

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High-throughput phase-distribution method to determine drug-cyclodextrin binding constants.

Zhi Chen1, Dujuan Lu, Stephen G Weber

  • 1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

Journal of Pharmaceutical Sciences
|April 23, 2008
PubMed
Summary
This summary is machine-generated.

A new high-throughput method accurately measures drug-cyclodextrin binding constants using a polymer film and cyclodextrin buffer. This faster, low-material protocol determines binding affinities for econazole with various cyclodextrins.

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Area of Science:

  • Analytical Chemistry
  • Physical Chemistry
  • Pharmaceutical Sciences

Background:

  • Drug-cyclodextrin interactions are crucial for drug formulation and delivery.
  • Accurate determination of binding constants is essential for optimizing drug solubility and stability.
  • Existing methods for measuring binding constants can be time-consuming and material-intensive.

Purpose of the Study:

  • To develop and validate a novel high-throughput method for measuring drug-cyclodextrin binding constants.
  • To compare the efficiency and material requirements of the new method with existing techniques.
  • To investigate the influence of drug concentration and pH on drug-cyclodextrin binding.

Main Methods:

  • A high-throughput assay utilizing a polyvinyl chloride (PVC) film with dioctyl sebacate (DOS) and a cyclodextrin-containing buffer in a 96-well microplate format.
  • Measurement of drug distribution ratios at varying cyclodextrin concentrations to calculate binding constants.
  • Determination of binding constants for econazole with six different cyclodextrins.

Main Results:

  • The developed method successfully determined binding constants for econazole with six cyclodextrins within 10 hours.
  • Binding constants (K(1:1)/10^3 M^-1) varied significantly across different cyclodextrins, with 2,6-di-O-methyl-beta-cyclodextrin showing the highest affinity.
  • Binding affinity decreased at higher drug concentrations and in acidic environments, suggesting drug self-association and protonation effects.

Conclusions:

  • The novel high-throughput method offers a faster and more material-efficient alternative to traditional techniques like phase-solubility analysis.
  • The method is suitable for studying drug-cyclodextrin interactions, including the impact of environmental factors like pH and drug concentration.
  • This approach facilitates rapid screening of drug-cyclodextrin interactions for pharmaceutical development.