Synthesis and Pharmacological Evaluation of Acrylate‐Based Gastrosparing NSAID Prodrugs

Abstract

Dexibuprofen and aceclofenac are well-known NSAID molecules, their oral use leads to gastrointestinal (GI) toxicity. To circumvent that GI toxicity, the prodrug approach is a better alternative. Hence, this research was undertaken to synthesize prodrugs of dexibuprofen and aceclofenac using acrylic polymers with degradable ester bonds. Dexibuprofen was linked to 2-hydroxypropyl methacrylate by an activated ester technique. The resulting material was copolymerized with 2-hydroxyethyl methacrylate and methyl methacrylate (in 1:3 mole ratios) by the free radical polymerization method, utilizing azoisobutyronitrile at 65-70°C. Similarly aceclofenac was also processed. The resulting prodrugs were characterized by IR, NMR, and elemental analysis. The synthesized prodrugs possess optimal physicochemical characteristics such as the intended molecular weight, lipophilicity, partition coefficient, and protein binding. The drug release on hydrolysis was studied in various fluids such as SGF (pH 1.2), SIF (pH 7.4), and SCF (pH 6.8), to establish the drug release kinetics. Pharmacological evaluation exhibited anti-inflammatory activity with remarkable reduction in ulcerogenicity compared to the parent drug. Under the conditions used, the prodrugs showed no antigenicity in Wistar rats. Thus, it was concluded that acrylic-based prodrugs were efficient in drug localization in the stomach, without gastric problems.

Oxaprozin prodrug as safer nonsteroidal anti‐inflammatory drug: Synthesis and pharmacological evaluation

“…The rate of hydrolysis of the dextran prodrug was enumerated as the percentage of drug hydrolyzed. The rate of hydrolysis and half‐life of the prepared prodrug were calculated using equation, r = (2.303/ t ) log ( a / a − x ), where r represents hydrolysis constant, t is the time in h, a is the initial concentration of prodrug, x is the amount of prodrug hydrolyzed, and ( a − x ) is the amount of prodrug remaining …”

“…Later SRBC were suspended in PBS containing serum were incubated for 24 h at 37°C. Hemagglutination condition was assessed …”