An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes

J Pharm Biomed Anal. 2008 Nov 4;48(3):685-93. doi: 10.1016/j.jpba.2008.06.025. Epub 2008 Jul 10.

Abstract

Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsules
  • Chemistry, Pharmaceutical
  • Computer Simulation
  • Delayed-Action Preparations / chemistry*
  • Diffusion
  • Dosage Forms
  • Drug Combinations
  • Equipment Design
  • Fasting / metabolism
  • Gastric Mucosa / metabolism
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Hydrogen-Ion Concentration
  • Hypromellose Derivatives
  • Levodopa / administration & dosage*
  • Levodopa / pharmacokinetics
  • Magnetic Resonance Imaging / methods*
  • Methylcellulose / administration & dosage
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / pharmacokinetics
  • Physiological Phenomena
  • Polymers / chemistry*
  • Solubility
  • Solvents / chemistry
  • Tablets
  • Technology, Pharmaceutical
  • Temperature
  • Time Factors
  • Water / chemistry

Substances

  • Capsules
  • Delayed-Action Preparations
  • Dosage Forms
  • Drug Combinations
  • Polymers
  • Solvents
  • Tablets
  • Water
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hypromellose Derivatives
  • Levodopa
  • Methylcellulose