Cosolubilization of non-polar drugs in polysorbate 80 solutions.
This study investigated the cosolubilization phenomenon of three non-polar drugs (hydrocortisone, beta-estradiol, and ethynylestradiol) in polysorbate 80 solutions. It was found that the solubility of any drug decreased in the presence of other steroidal compounds. In an attempt to understand the observation, the author proposed a model to describe and to predict the drug solubility in the presence of other non-polar drugs in a non-ionic surfactant. The model indicates that, in a non-ionic surfactant solution that contains both drugs D(a) and D(b), the total solubility [D(a)(tot)] is related not only to the physical chemical properties of D(a) (micellar equilibrium constant K(a), the intrinsic solubility [D(a)]), as well as the total surfactant concentration [S(tot)], it is also related to the physical chemical properties of the D(b). Mathematically, the [D(a)(tot)] decreases as the product of the micellar equilibrium constant K(b) and the intrinsic solubility [D(b)] increases. The model was also put to the test by comparing the cosolubilization data obtained experimentally with the data calculated from the proposed model. The fact that these two sets of data were in good agreement lent strong support to the newly proposed model.
Li
Ping
P
Pharmaceutical Development, Novartis Pharmaceutical Corporation, East Hanover, NJ 07936, USA. ping.li@pharma.novartis.com
Zhao
Luwei
L
D004364:Pharmaceutical Preparations / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry*; D012995:Solubility
D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D011136:Polysorbates