Oral controlled release dosage forms: dissolution versus diffusion

Expert Opin Drug Deliv. 2020 Jun;17(6):791-803. doi: 10.1080/17425247.2020.1750593. Epub 2020 Apr 20.


Introduction: Controlled release (CR) dosage forms comprise a wide range of technologies, which modify the drug pharmacokinetic (PK) profile by avoiding the immediate release (IR) of the active pharmaceutical ingredient (API). They are particularly of interest in chronic diseases, for narrow therapeutic index drugs or for targeting a particular gastrointestinal tract (GI) segment.

Areas covered: Diffusion and dissolution limited controlled release systems are described in terms of release kinetics and formulation strategies with e xamples marketed or under development. Additionally, the physiological variables affecting the release (such as fluid pH, volume and composition, physical forces, and transit times) and the in vitro dissolution techniques currently available are reviewed.

Expert opinion: Selection of the appropriate release mechanism is not a straightforward process, as it requires a balance based on the desired target, the API properties and the technological challenges of the dosage form structure. Diffusion, dissolution or a combination of both could be adequate without an absolute superiority of one mechanism over the other. The combination of in vivo predictive dissolution systems, with mathematical modeling of the release mechanism and its correlation with formulation composition could help to design prototype candidates, with enhanced probabilities of success in human clinical trials.

Keywords: Oral controlled release; diffusion; dissolution; formulation selection; predictive dissolution; release kinetics.

Publication types

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

MeSH terms

  • Administration, Oral
  • Delayed-Action Preparations*
  • Diffusion
  • Dosage Forms
  • Gastrointestinal Tract / metabolism*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / chemistry
  • Solubility


  • Delayed-Action Preparations
  • Dosage Forms
  • Pharmaceutical Preparations