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Related Concept Videos

Factors Influencing Drug Absorption: Drug Dissolution01:27

Factors Influencing Drug Absorption: Drug Dissolution

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...
Methods for Studying Drug Absorption: In vitro01:16

Methods for Studying Drug Absorption: In vitro

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.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
Methods for Studying Drug Absorption: In situ01:09

Methods for Studying Drug Absorption: In situ

In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
Factors Influencing Drug Absorption: Physicochemical Parameters01:22

Factors Influencing Drug Absorption: Physicochemical Parameters

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

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

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 in drug...
Bioavailability Enhancement: Drug Solubility Enhancement01:16

Bioavailability Enhancement: Drug Solubility Enhancement

Bioavailability is a critical factor in determining a drug's effectiveness. It refers to the proportion of a drug that enters the circulation when introduced into the body and is, as a result, able to have an active effect. Enhancing bioavailability is essential for drugs with poor solubility, as it can significantly impact their therapeutic efficacy. Various methods are employed to increase the solubility of drugs, thereby enhancing their bioavailability.Micronization and nanonization are...

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Related Experiment Video

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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
05:08

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Published on: September 20, 2017

Computational oral absorption simulation for low-solubility compounds.

Kiyohiko Sugano1

  • 1Global Research & Development, Sandwich Laboratories, Research Formulation, Pfizer Inc., CT13 9NJ, Sandwich, Kent, UK. Kiyohiko.Sugano@pfizer.com

Chemistry & Biodiversity
|November 26, 2009
PubMed
Summary

Bile micelles significantly impact oral drug absorption by influencing solubility, dissolution, and permeability. Modified equations accounting for micelle partitioning and diffusion are crucial for predicting drug behavior and the food effect.

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Area of Science:

  • Pharmacokinetics
  • Physical Chemistry

Background:

  • Bile micelles are critical for oral absorption of poorly soluble drugs.
  • They influence drug solubility, dissolution rate, and permeability.
  • Existing models often overlook micelle-specific effects.

Purpose of the Study:

  • To modify existing equations to incorporate bile micelle behavior.
  • To improve predictions of oral absorption for low-solubility compounds.
  • To elucidate the role of bile micelles in the food effect on drug absorption.

Main Methods:

  • Modified Henderson-Hasselbalch and Nernst-Brunner equations were developed.
  • Incorporated bile-micelle partition coefficients and effective diffusion coefficients.
  • Validated theoretical models with in vivo and clinical oral absorption data.

Main Results:

  • Modified equations accurately predict pH-solubility profiles and dissolution rates.
  • Bile micelle diffusion coefficients are significantly lower (8-18 fold) than monomer diffusion.
  • Effective diffusion in the unstirred water layer and free drug fraction are key for permeability.

Conclusions:

  • Theoretical modifications enhance the prediction of oral drug absorption involving bile micelles.
  • Understanding micelle dynamics is vital for explaining the food effect on drug bioavailability.
  • These insights aid in optimizing drug formulation and predicting in vivo performance.