The effect of alpha-tocopherol on the in vitro solubilisation of lipophilic drugs.
alpha-Tocopherol is an excellent solvent for many poorly soluble drugs. The aim of this work was to study whether or not the presence of alpha-tocopherol has an influence on the solubilisation of poorly soluble drugs in simulated intestinal fluids (SIF). The solubilizing capacity of mixed micelles containing alpha-tocopherol towards three lipophilic drugs was investigated. The solubilisation of alpha-tocopherol in an aqueous micellar phase was increased by the addition of monoglycerides (MG) and free fatty acids (FFA), preferably of medium chain length, as compared to a simple bile salt solution. The addition of alpha-tocopherol to mixed micellar solutions seems to have an effect on the solubilizing capacity, which can be correlated to the partition coefficient of the drug to be solubilised. A positive effect on the solubilisation of griseofulvin and felodipine was found. For a highly lipophilic drug (Lu28-179), a positive effect on solubilisation was observed only in media containing MG and FFA of medium chain length. Generally, alpha-tocopherol cannot be considered an important factor for the solubilisation of highly lipophilic drugs in SIF. The presence of lipolytic digestion products (LDP) of the proper chain length in relation to the drug to be solubilised is much more important.
Nielsen
P B
PB
Dumex-Alpharma A/S, Dalslandsgade 11, 2300 S, Copenhagen, Denmark.
Müllertz
A
A
Norling
T
T
Kristensen
H G
HG
D000935:Antifungal Agents / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006118:Griseofulvin / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D012995:Solubility / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
D000935:Antifungal Agents; D008055:Lipids; D014810:Vitamin E; D006118:Griseofulvin