Model for the Analysis of Membrane-Type Dissolution Tests for Inhaled Drugs

Mol Pharm. 2020 Jul 6;17(7):2426-2434. doi: 10.1021/acs.molpharmaceut.0c00163. Epub 2020 Jun 15.

Abstract

Impactor-type dose deposition is a common prerequisite for dissolution testing of inhaled medicines, and drug release typically takes place through a membrane. The purpose of this work is to develop a mechanistic model for such combined dissolution and release processes, focusing on a drug that initially is present in solid form. Our starting points are the Noyes-Whitney (or Nernst-Brunner) equation and Fick's law. A detailed mechanistic analysis of the drug release process is provided, and approximate closed-form expressions for the amount of the drug that remains in solid form and the amount of the drug that has been released are derived. Comparisons with numerical data demonstrated the accuracy of the approximate expressions. Comparisons with experimental release data from literature demonstrated that the model can be used to establish rate-controlling release mechanisms. In conclusion, the model constitutes a valuable tool for the analysis of in vitro dissolution data for inhaled drugs.

Keywords: dissolution; drug delivery; formulation development; lung; mathematical model.

MeSH terms

  • Administration, Inhalation
  • Chemistry, Pharmaceutical
  • Data Accuracy
  • Drug Compounding / methods*
  • Drug Delivery Systems / methods*
  • Drug Liberation*
  • Humans
  • Membranes, Artificial
  • Models, Theoretical*
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / chemistry
  • Powders
  • Solubility

Substances

  • Membranes, Artificial
  • Pharmaceutical Preparations
  • Powders