In vitro digestion kinetics of excipients for lipid-based drug delivery and introduction of a relative lipolysis half life

Drug Dev Ind Pharm. 2012 Oct;38(10):1262-9. doi: 10.3109/03639045.2011.645834. Epub 2011 Dec 30.

Abstract

Background: Lipid-based drug delivery systems are widely used for enhancing the solubility of poorly water soluble drugs in the gastro-intestinal tract. Following oral intake, lipid systems undergo digestion in the stomach as well as the intestine. Lipolysis is here a complex process at the oil/water interface, influenced by numerous factors.

Purpose: To study the digestibility of nine excipients often used in lipid-based drug delivery systems. In addition, we introduced a mathematical model to describe in vitro lipolysis kinetics. A relative lipolysis half life was defined using the reference excipient medium-chain triglycerides.

Methods: Using pH-stat equipment, the NaOH consumption was determined in an in vitro lipolysis assay.

Results: We identified two classes of excipients. Some additives were partially hydrolysed, whereas other excipients displayed complete lipolysis. For the latter class, a simplified mathematical model provided a good first approximation of initial lipolysis kinetics.

Conclusions: Digestion characterization of excipients is important for the development of lipid-based delivery systems. The applied kinetic model and the concept of a relative lipolysis half life seemed to be promising tools for comparing in vitro lipolysis results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Digestion
  • Drug Delivery Systems / methods*
  • Excipients / chemistry*
  • Gastrointestinal Tract / metabolism
  • Half-Life
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lipids / administration & dosage*
  • Lipids / chemistry*
  • Lipolysis
  • Models, Theoretical
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / chemistry*
  • Sodium Hydroxide / chemistry
  • Solubility
  • Triglycerides / chemistry

Substances

  • Excipients
  • Lipids
  • Pharmaceutical Preparations
  • Triglycerides
  • Sodium Hydroxide