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Related Concept Videos

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...
Solubility03:00

Solubility

Solution, Solubility, and Solubility Equilibrium
A solution is a homogeneous mixture composed of a solvent, the major component, and a solute, the minor component. The physical state of a solution—solid, liquid, or gas—is typically the same as that of the solvent. Solute concentrations are often described with qualitative terms such as dilute (of relatively low concentration) and concentrated (of relatively high concentration).
In a solution, the solute particles (molecules, atoms, and/or ions)...
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...
Passive Diffusion: Overview and Kinetics01:17

Passive Diffusion: Overview and Kinetics

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.
When administered orally, drugs establish a substantial concentration gradient between the gastrointestinal (GI) lumen and the bloodstream, expediting their diffusion into...
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...
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...

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Characteristics of Precipitation-formed Polyethylene Glycol Microgels Are Controlled by Molecular Weight of Reactants
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PLGA erosion: solubility- or diffusion-controlled?

Martin Körber1

  • 1College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169, Berlin, Germany. koerberm@zedat.fu-berlin.de

Pharmaceutical Research
|August 20, 2010
PubMed
Summary

Poly(lactic-co-glycolic acid) (PLGA) erosion is driven by the formation of water-soluble oligomers, not diffusion. This finding helps predict drug release from PLGA delivery systems.

Area of Science:

  • Polymer science
  • Materials science
  • Biomedical engineering

Background:

  • Poly(lactic-co-glycolic acid) (PLGA) is widely used in drug delivery systems.
  • Understanding PLGA degradation and erosion is crucial for predicting drug release profiles.
  • Current models often assume diffusion-limited erosion, which may not accurately reflect the process.

Purpose of the Study:

  • To quantify the formation of water-soluble PLGA oligomers over time during degradation.
  • To correlate calculated oligomer formation with the observed erosion of PLGA matrices.
  • To develop a model for predicting drug release based on PLGA erosion mechanisms.

Main Methods:

  • Characterization of PLGA using gel permeation chromatography (GPC) to determine molecular weight distribution (MWD).

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  • Analysis of degradation and erosion behavior of PLGA.
  • Implementation of pseudo-first-order reaction kinetics into the MWD function to model oligomer formation.

    • Main Results:

    • PLGA exhibited a lognormal distribution of molecular weights.
    • Calculated water-soluble oligomer formation closely matched measured erosional mass loss.
    • PLGA erosion was found to be solubility-controlled, driven by oligomer formation, rather than diffusion-limited.

    Conclusions:

    • The formation of soluble PLGA oligomers accurately predicts erosional mass loss.
    • Bulk erosion of PLGA is a degradation-controlled dissolution process.
    • This understanding facilitates more accurate forecasting of drug release from PLGA delivery systems.