Drug Partitioning I: Nonemulsifying Method for Measuring Distribution Coefficients

A simple rocking apparatus has been constructed for routine determination of distribution coefficients. With this apparatus, up to 36 two-phase samples in cylindrical tubes are equilibrated by rocking the horizontal tubes at 1 c.p.m. (cycle per minute) through an arc of 45°. This rocking causes the interface between the two immiscible phases to expand and contract slowly; it also causes the shape of each phase to vary constantly. These two actions facilitate uniform distribution of solute within each phase and facilitate drug transfer from one phase to the other. Emulsion formation is negligible since little turbulence is created. Considerable man hours are saved with some pharmaceutical systems if the rocking method, rather than the usual shake-out method, is used. The experimental method is simple and, where shake-out methods can be employed, gives results which are in agreement with results from shake-out methods. Data for the distribution of ephedrine, chlorpromazine and its salts, several benzoic acid derivatives, hexachlorophene, and bithionol are presented. Pharmaceutical applications of partitioning are discussed.