Toward the establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range of representative formulations.
The Lipid Formulation Classification System Consortium is an industry-academia collaboration, established to develop standardized in vitro methods for the assessment of lipid-based formulations (LBFs). In this first publication, baseline conditions for the conduct of digestion tests are suggested and a series of eight model LBFs are described to probe test performance across different formulation types. Digestion experiments were performed in vitro using a pH-stat apparatus and danazol employed as a model poorly water-soluble drug. LBF digestion (rate and extent) and drug solubilization patterns on digestion were examined. To evaluate cross-site reproducibility, experiments were conducted at two sites and highly consistent results were obtained. In a further refinement, bench-top centrifugation was explored as a higher throughput approach to separation of the products of digestion (and compared with ultracentrifugation), and conditions under which this method was acceptable were defined. Drug solubilization was highly dependent on LBF composition, but poorly correlated with simple performance indicators such as dispersion efficiency, confirming the utility of the digestion model as a means of formulation differentiation.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia.
Hywel D
HD
Williams
Philip
P
Sassene
Karen
K
Kleberg
Jean-Claude
JC
Bakala-N'Goma
Marilyn
M
Calderone
Vincent
V
Jannin
Annabel
A
Igonin
Anette
A
Partheil
Delphine
D
Marchaud
Eduardo
E
Jule
Jan
J
Vertommen
Mario
M
Maio
Ross
R
Blundell
Hassan
H
Benameur
Frédéric
F
Carrière
Anette
A
Müllertz
Christopher J H
CJ
Porter
Colin W
CW
Pouton
D002498:Centrifugation / Q000592:standards; D002626:Chemistry, Pharmaceutical / Q000592:standards; D003613:Danazol / Q000737:chemistry* / Q000378:metabolism / Q000592:standards; D004063:Digestion; D004337:Drug Carriers; D017408:Guidelines as Topic; D057166:High-Throughput Screening Assays / Q000592:standards*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry* / Q000592:standards; D015588:Observer Variation; D012015:Reference Standards; D015203:Reproducibility of Results; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards*
D004337:Drug Carriers; D008055:Lipids; D003613:Danazol