Improving the lipophilicity of piroxicam by silyl groups and its confirmation by RP-HPLC and computational chemistry

The painkiller piroxicam was examined in this research study. Two derivatives dimethyl-tert-butyl-silyloxy and triethyl silyloxy piroxicam were synthesized to improve the drug's lipophilicity and permeability. Thin layer chromatography was used to separate silylated derivatives, and SN2 was the reaction mechanism. FT-IR and 1 H-NMR spectroscopy were used to identify the produced compounds. Reverse phase high performance liquid chromatography (RP-HPLC) was employed to examine the lipophilicity of the silylated derivatives of piroxicam. Due to the non-polar nature of the column used in this device and the polarity of piroxicam and its derivatives, the retention time of silylated derivatives was longer in the column compared to the original piroxicam, due to the inherent nature of these materials which have high non polar properties. The results show an acceptable increase in the lipophilicity of the silylated derivatives compared to piroxicam. To evaluate the hydrophobic properties of drugs e.g., piroxicam and the silyl derivatives of piroxicam, the distribution of the species around the drugs were investigated in a Water/Octanol mixture using molecular dynamics simulation (MDS). Results of the radial distribution functions (RDFs) and continuous hydrogen bond networks suggest a favorable interaction between Octanol molecules and the silyl derivatives of piroxicam compared to piroxicam.