Spectrophotometric determination of drug partition coefficients in dimyristoyl-L-alpha-phosphatidylcholine/water: a comparative study using phase separation and liposome suspensions

The partition coefficients (Kp) between lipid bilayers of dimyristoyl-L-alphaphosphatidylcholine (DMPC) unilamellar liposomes and water were calculated for four drugs, chlordiazepoxide (a benzodiazepine), isoniazid and rifampicin (tuberculostatic drugs) and griseofulvin (an antifungal antibiotic), using spectrophotometric data and two different approaches. In one, spectrophotometric data were obtained in liposome suspensions and the values of Kp were determined from second derivative intensities. In the other, the aqueous and lipid phases were separated by filtering through a Centricon filter unit prior to spectrophotometric determination of drug concentration in each phase. Both methods provide precise and accurate values for the partition coefficient of the drugs in water (Hepes)/DMPC media. None of them presents a clear advantage in the total time needed for the determinations, but for drugs which absorb near or below 275nm, the need to eliminate liposome scattering may favour the phase separation method.