چکیده (انگلیسی):

The current work envisages synthesis of an ester prodrug of flurbiprofen whereby its carboxylic
group was condensed with a skeletal muscle relaxant methocarbamol, with the aim
of synergistic activity of two drugs, avoid flurbiprofen mediated gastro-intestinal damage
and minimize the ulceration tendency of flurbiprofen. The synthesized prodrug was characterized
and confirmed by physicochemical and spectroscopic studies. Solubility and partition
coefficient studies indicated an increased lipophilicity and thus better suitability for oral
administration than the parent drugs and the protein binding studies revealed a low protein
binding capacity of the mutual prodrug. Subsequently, in-vitro hydrolysis was studied in different
pH, simulated gastric fluid, simulated intestinal fluid and plasma and quantitative
evaluation was performed by high performance liquid chromatography. It was found that
the prodrug remained unhydrolyzed in the stomach after absorption however, underwent
rapid cleavage by the esterases in blood to give the parent drug. Furthermore, the mutual
ester prodrug was evaluated for its anti-inflammatory, analgesic, skeletal muscle relaxation,
ulcerogenic and total acid content activity and was found to possess comparable activity
with that of the parent drugs. Microscopic structures of the stomach tissues revealed significant
reduction in gastric ulcer formation of mice gastric mucosa as compared to parent
carboxylic acid drug.