BILE SALT-PHOSPHOLIPID MIXED MICELLES AS SOLUBILIZERS FOR WATER-INSOLUBLE DRUGS

Beena ASHOK*, Sharon AYD**, Kyonghee SON*, Hayat ÖNYÜKSEL*,***,°

Departments of *Biopharmaceutial Sciences,***, Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60612, **Advanced Life Sciences, Woodridge, Illinois 60517
oCorresponding author e-mail: hayat@uic.edu

Summary:
Solubulization of water-insouble drugs is still a challenge in the pharmaceutical industry. This review outlines the use of bile salt-phospholipid micelles as a means to address this issue. Bile salt/phospholipid (BS/PL) mixed micelles improve solubilization of water-insouble drugs and possess reduced toxicity compared to BS simple micelles. The other significant advantages of these systems are prevention of drug precipitation upon aqueous dilution and their existance as clear isotropic solutions suitable for injection. From a manufacturing perspective, mixed micellar solutions can be easily freeze-dried and sterilized by filtration. Pain on infection has also been reported to be reduced with the use of these systems. Micelle-to-vesicle transition on aqueous dilution is an important property which has to be considered while dealing with these systems. A critical lipid composition can be determined and fixed wherein there is a linearrelationship over a certain range between the phospholipid/bile salt ratio and the total lipid concentration. In this range the concentration of mixed micelles can be varied without significantly changing the structure of the micelle. Two predictive models have been developed for solubilization in mixed micelles. The factors affecting the drug solubilization in the micelles and precilinical and clinical studies are also reviewed.

Keywords:
Solubilization, Bile salt phospholipid mixed micelles, Water insoluble drugs, Proliposomes