Dimitrova B, Doytchinova I, Zlatkova M
Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, Bulgaria.
J Pharm Biomed Anal. 2000 Nov;23(6):955-64. doi: 10.1016/s0731-7085(00)00370-8.
The aim of this study was to assess the potency of the reversed-phase high-performance liquid chromatography (RP-HPLC) for in vitro evaluation of the distribution behavior of common drugs between one of the generally used suppository bases Witepsol H15 and the rectal liquid which is imitated by a phosphate buffer, pH 7.2. The distribution coefficients (log K) of nine compounds--paracetamol, caffeine, diclofenac, propyphenazone, indomethacin, codeine base, codeine phosphate, phenobarbital acid and phenobarbital sodium salt were determined by the classical shake-flask' method followed by RP-HPLC quantitative assay. The capacity factors log k' of the compounds were determined on reversed-phase C18 column at a number of methanol-5 mM phosphate buffer, pH 7.2 mobile phases containing different percentages of methanol (phiMeOH). The apparent capacity factors log k(w)app were derived by extrapolation of the methanol concentration to zero and using the correction for ionization, the real capacity factors log k'(w) were calculated. The lipophilicity of the compounds was assessed by the partition coefficients CLOGP and the distribution coefficients CLOGD7.2, calculated for the n-octanol-water system. Correlations between log k'(w) and CLOGP, log k(w)app and CLOGD7.2, log k(w)app and log K were found. The last correlation indicated that the parameter log k(w)app was suitable for evaluating the distribution behavior of the studied drugs in the examined Witepsol H15-rectal liquid system. The predictive power of this correlation was tested by a set of nine non-congeners. It was shown that the classical 'shake-flask' method for determination of the distribution behavior of the studied drugs between the suppository base Witepsol H15 and the phosphate buffer, pH 7.2 might be replaced by the RP-HPLC technique due to its priorities of rapid, stable and reproducible experiments.
