Reversed-phase high-performance liquid chromatography for evaluating the distribution of pharmaceutical substances in suppository base–phosphate buffer system

Abstract

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 H 15 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 C 18 column at a number of methanol–5 mM phosphate buffer, pH 7.2 mobile phases containing different percentages of methanol ( φ MeOH). 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 CLOGD 7.2, calculated for the n-octanol–water system. Correlations between log k′ w and CLOGP, log k′ w app and CLOGD 7.2, 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 H 15-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 H 15 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.