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

The partition coefficients (K-p) between lipid bilayers of dimyristoyl-L-al pha -phosphatidylcholine (DMPC) unilamellar liposomes and water were calcul ated for four drugs, chlordiazepoxide (a benzodiazepine), isoniazid and rif ampicin (tuberculostatic drugs) and griseofulvin (an antifungal antibiotic) , using spectrophotometric data and two different approaches. In one, spect rophotometric data were obtained in liposome suspensions and the values of Kp were determined from second derivative intensities. In the other, the aq ueous and lipid phases were separated by filtering through a Centricon filt er unit prior to spectrophotometric determination of drug concentration in each phase. Both methods provide precise and accurate values for the partit ion coefficient of the drugs in water (Hepes)/DMPC media. None of them pres ents a clear advantage in the total time needed for the determinations, but for drugs which absorb near or below 275 nm, the need to eliminate liposom e scattering may favdour the phase separation method. (C) 2001 Elsevier Sci ence B.V. All rights reserved.