Distribution modeling of diazepam and chlorpheniramine between aqueous and non-polar phases in the presence of soy lecithin

Abstract Under certain conditions many pharmaceuticals can accumulate in organic phases due to their low polarity. It is possible that with such drugs in the presence of other substances, like surfactants, an accumulation phenomenon may occur. In this work, a study has been performed in order to determine the influence of surfactants, like soy lecithin, on the behavior of diazepam and chlorpheniramine distribution between an organic and an aqueous phase. First, the extraction of CPM and DZP without soy lecithin was evaluated. As expected, the molecular form (non-charged) were the best extracted. The extraction of CPM and DZP were close to 100% at pH 8.7 and pH 5, respectively. On the other hand, the results show that the presence of a surfactant increases the drug accumulation into the organic phase towards lower values of pH, where the predominated forms of drugs are the protonated for chlorpheniramine (CPMH+) and neutral for diazepam (DZP), this being more important in the chlorpheniramine case which is extracted as CPMH+.SL. A model for extraction of both drugs was developed and tested: in absence of soy lecithin partition coefficients of 181.7 and 19.1 were obtained for chlorpheniramine and diazepam, respectively. In presence of soy lecithin, the model considers the presence of CPMH+ and CPMH2+ in the aqueous phase, meanwhile in the organic phase the model takes into account as extracted species CPMH+.SL− and CPM. The extraction constants values obtained were KextCPMH+ = 0.20 L.mol−1 and Kext(CPMH2)2+ = 1.89*10−6.