Mixed micelle formation with phosphatidylcholines: The influence of surfactants with different molecule structures

作者：Rupp Christopher; Steckel Hartwig; Mueller Bernd W

来源：International Journal of Pharmaceutics, 2010, 387(1-2): 120-128.

DOI：10.1016/j.ijpharm.2009.12.018

• Phosphatidylcholine
• Sucrose esters
• Packing parameter
• Mixed micelles

The number of mixed micellar(MM) drug products being introduced into the commercial pharmaceutical market is very limited although there is need for alternative dosage forms for poorly soluble active drug substances. While known systems are composed of phosphatidylcholine and bile salts, it was the aim of this study to investigate if alternative surfactants are able to form isotropically clear solutions over a broad range of concentrations and at higher ratios of phosphatidylcholine (PC). It was a particular challenge of this work to find a MM system with a unimodal particle size distribution since it is known that surfactants often form vesicles with phospholipids instead of MM. The theoretical approach behind this work was the transfer of the packing parameter concept, which describes the molecular association of one amphiphilic species, to the organisation behaviour of two different amphiphilic species (water-insoluble phospholipid + surfactant leading to MM). Therefore the influence of the surfactant molecular geometry on the ability to form MM with phospholipids was investigated. A homologous series of two different surfactant classes, namely polyglycerol esters and sucrose esters, with a large hydrophilic head region leading to a smaller packing parameter were analysed regarding their ability to form clear MM solutions with PC. For comparison, surfactants with no strictly defined partition between a polar head and a non-polar tail (e.g. Poloxamer 188) were tested. Decaglycerol laurate and especially sucrose laurate (SL) were superior compared to all other tested surfactants with respect to their ability to form clear solutions with hydrogenated PC (hPC) at a higher ratio and over a broad range of concentrations while unsaturated PC showed an inferior performance to form MM. The favourite MM system composed of SL with 0.5 weight fractions of hPC formed about 20 nm sized MM in a concentration range of 1.0-80 mg/mL and showing a unimodal particle size distribution with a PDI value < 0.1. The results of the study have shown that the transferred packing parameter concept is applicable to the tested surfactants to describe their ability forming mixed micelles with PC.

• 出版日期2010-3-15