A biorelevant dissolution stress test device - background and experiences

Expert Opin Drug Deliv. 2010 Nov;7(11):1251-61. doi: 10.1517/17425247.2010.527943.

Abstract

Importance of the field: The prediction of the in vivo drug release characteristics of modified release (MR) oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development.

Areas covered in this review: To improve the predictive power of dissolution testing, the authors recently developed a new dissolution test apparatus that simulates physical conditions of the gastrointestinal (GI) passage of MR dosage forms. The simulation includes pressure force exerted by GI motility, shear stress force generated during phases of GI transport and intermittent contact with intestinal fluids while the dosage form is located in an intestinal air pocket.

What the reader will gain: The article briefly describes selected aspects of GI tract physiology, evolution and goals of dissolution testing as well as the development and use of test devices that are intended to simulate GI tract conditions. The data are discussed in the light of the test results obtained with the new dissolution stress test device developed by the authors' group. Achievements reported from 1986 to 2010 are referred to.

Take home message: The new apparatus was evaluated using extended release (ER) tablets of nifedipine and diclofenac. The dissolution characteristics of some of the tested products were strongly dependent on the test conditions and could be distinctly influenced by the mechanical stress events of biorelevant intensity. Results of these experiments thus indicated that a high sensitivity of dosage forms to GI-specific physical conditions has to be regarded as a major cause of irregularities in the drug release profiles, which may result in fluctuations of the individual drug plasma concentration profiles, as, for example, caused by dose dumping.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Chemistry, Pharmaceutical / methods*
  • Delayed-Action Preparations
  • Diclofenac / administration & dosage
  • Diclofenac / chemistry
  • Gastrointestinal Motility
  • Gastrointestinal Tract / metabolism*
  • Humans
  • Nifedipine / administration & dosage
  • Nifedipine / chemistry
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / chemistry*
  • Solubility
  • Stress, Mechanical
  • Tablets

Substances

  • Delayed-Action Preparations
  • Pharmaceutical Preparations
  • Tablets
  • Diclofenac
  • Nifedipine