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


OBJECTIVE
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.
University of Basel, Division of Pharmaceutical Technology, Basel, Switzerland.
Yvonne E
YE
Arnold
Georgios
G
Imanidis
Martin
M
Kuentz
D000284:Administration, Oral; D004063:Digestion; D016503:Drug Delivery Systems / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000378:metabolism; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry*; D008066:Lipolysis; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D012972:Sodium Hydroxide / Q000737:chemistry; D012995:Solubility; D014280:Triglycerides / Q000737:chemistry
D005079:Excipients; D008055:Lipids; D004364:Pharmaceutical Preparations; D014280:Triglycerides; D012972:Sodium Hydroxide