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Related Concept Videos

Factors Influencing Drug Absorption: Drug Dissolution01:27

Factors Influencing Drug Absorption: Drug Dissolution

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The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
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Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

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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...
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Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

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Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
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Factors Affecting Dissolution: Particle Size and Effective Surface Area01:23

Factors Affecting Dissolution: Particle Size and Effective Surface Area

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Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
913
Factors Influencing Drug Absorption: Physicochemical Parameters01:22

Factors Influencing Drug Absorption: Physicochemical Parameters

341
The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
341
Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

Factors Influencing Drug Absorption: Pharmaceutical Parameters

164
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
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Multi-Compartmental Dissolution Method, an Efficient Tool for the Development of Enhanced Bioavailability

Miklós Tamás Katona1,2, Lili Nagy-Katona3, Réka Szabó2

  • 1Department of Pharmaceutical Chemistry, Semmelweis University, 7 Hőgyes Endre Street, H-1092 Budapest, Hungary.

Pharmaceutics
|March 29, 2023
PubMed
Summary
This summary is machine-generated.

The Gastrointestinal Simulator (GIS) effectively predicts drug performance by modeling in vivo behavior for poorly soluble drugs. This advanced dissolution method offers superior bioavailability enhancement insights compared to traditional approaches.

Keywords:
BCS Class IIaIVIVCibuprofenmulti-compartmental dissolutionsolubilitysupersaturation

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Pharmaceutical Technology
  • Biopharmaceutics

Background:

  • Enhancing the bioavailability of poorly soluble drugs is crucial for effective therapeutic outcomes.
  • Understanding drug absorption mechanisms through in vitro modeling is essential for formulation development.
  • Biopharmaceutics Classification System (BCS) Class IIa compounds present significant formulation challenges due to poor solubility.

Purpose of the Study:

  • To evaluate the Gastrointestinal Simulator (GIS) as a predictive tool for in vivo drug performance.
  • To assess the GIS's applicability for Biopharmaceutics Classification System (BCS) Class IIa compounds.
  • To establish an in vitro-in vivo correlation (IVIVC) for immediate-release ibuprofen formulations.

Main Methods:

  • Utilized a multi-compartmental dissolution model, the Gastrointestinal Simulator (GIS).
  • Tested four immediate-release ibuprofen 200 mg formulations (acid, sodium salt, lysine salt, soft-gelatin capsule) in fasted biorelevant media.
  • Established a Level A in vitro-in vivo correlation (IVIVC) using published in vivo data and simulated plasma concentration profiles.

Main Results:

  • The GIS demonstrated supersaturation for rapid-dissolving formulations in the gastric compartment, impacting duodenal and jejunal concentrations.
  • Simulated pharmacokinetic parameters closely matched published clinical study data.
  • The GIS method showed superior performance compared to the traditional United States Pharmacopeia (USP) dissolution method.

Conclusions:

  • The Gastrointestinal Simulator (GIS) is a valuable tool for predicting the in vivo performance of BCS Class IIa compounds.
  • The GIS facilitates the optimization of formulations to enhance the bioavailability of poorly soluble acidic drugs.
  • This in vitro modeling approach offers significant advantages over conventional dissolution testing methods for complex drug formulations.