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Creating Adhesive and Soluble Gradients for Imaging Cell Migration with Fluorescence Microscopy
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Published on: April 4, 2013

PAMPA - excipient classification gradient map.

Stefanie Bendels1, Oksana Tsinman, Björn Wagner

  • 1Pharmaceutical Division, F. Hoffmann-La Roche Ltd., PRBD-C, CH-4070, Basel, Switzerland.

Pharmaceutical Research
|October 21, 2006
PubMed
Summary

Excipients significantly alter drug permeability across artificial membranes, enhancing weak acids but reducing weak bases. This study highlights the Double-Sink PAMPA method

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Area of Science:

  • Pharmacokinetics and Drug Delivery
  • Physicochemical Properties of Drugs

Background:

  • Sparingly soluble drugs pose challenges in oral drug delivery due to poor absorption.
  • Excipients are commonly used in formulations to improve drug solubility and bioavailability.
  • Understanding excipient-drug interactions is crucial for predicting in vivo performance.

Purpose of the Study:

  • To investigate the impact of various excipients on the membrane permeability of sparingly soluble drugs.
  • To evaluate the utility of the Double-Sink Parallel Artificial Membrane Assay (PAMPA) for assessing excipient effects.
  • To establish a ranking of excipient influence on drug permeability.

Main Methods:

  • Employed the Double-Sink PAMPA assay to measure artificial membrane permeability.
  • Tested eight sparingly soluble drugs at clinically relevant excipient concentrations.
  • Utilized measured ionization constants to correct for aqueous boundary layer effects and determine intrinsic permeability.

Main Results:

  • Excipients enhanced the intrinsic permeability of weak acids (up to 100-fold) and depressed that of weak bases (up to 270-fold).
  • A clear ranking of excipient effects was established, with agents like sodium taurocholate (NaTC) and polyethylene glycol (PEG400) showing significant impact.
  • Drug permeability ranking was also determined, with mefenamic acid and glybenclamide showing the most pronounced changes.

Conclusions:

  • The Double-Sink PAMPA method is a valuable, cost-effective tool for preclinical assessment of excipient effects on drug permeability.
  • PAMPA-Mapping offers a useful visualization for drug delivery screening and formulation development.
  • Excipient selection can significantly modulate the permeability of sparingly soluble drugs, impacting their potential efficacy.