Prodrug Designing of NSAIDs

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), commonly used for the treatment of chronic inflammatory diseases suffer from several undesired side effects, the most important being gastrointestinal (GI) irritation and ulceration. The prodrug designing is one of the several strategies used to overcome this drawback. The rationale behind the prodrug concept is to achieve temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption. In this paper, a review on the concept of prodrugs designing of NSAIDs to improve their efficacy and reduce the toxicity is being presented.

Esterification of glycerol and ibuprofen in solventless media catalyzed by free CALB: Kinetic modelling

“…The chronic use by oral administration of NSAID can cause gastric mucosal damage, more concretely stomach ulceration, bleeding and perforation [2]. In recent years, prodrugs (bioreversble derivates) of NSAID have been developed to block the carboxylic acid group of NSAIDs as a way of reducing or avoiding the gastrointestinal (GI) side effects [3]. At the present time, prodrug of NSAID have been used as suspensions, emulsion, microemulsion and nanoemulsions [4].…”

“…In addition, as they are natural esterase substrates, esters are suitably labile, in vivo [3]. Also, some hydrophilic esters are more soluble and biodisponible than the original drug [9].…”

“…dard errors or, in other words, the lowest t-values or narrowest intervals of error at 95% confidence. Considering the p-values for all of them (<0.0001), all models are sound enough to be tested (conclusion that could be reached considering the results from the Multivariable fitting of the selected kinetic model (model3) to experimental data at 50 and 80 • C for (a-b) the low water content set of runs and (c-d) the high water content set of runs.…”

A Stability-Indicating RP-HPLC-UV Method for Determination and Chemical Hydrolysis Study of a Novel Naproxen Prodrug

“…Because NSAIDs are almost always used chronically especially by the elderly, their dangerous gastrointestinal (GI), cardiac, and renal side effects constitute a problem hindering their use. The prodrug approach is an effective way to mask the carboxylic acid group of NSAIDs, which is the main culprit in the GI adverse effects [3,4].…”

Synthesis and characterization of novel pyrazolone derivatives

“…During the discovery of pyrazolone, they were only known as NSAIDs [2] but, since year 2000, they play versatile role in several complications like cerebral ischemia and cardiovascular diseases [3]. The chemistry of pyrazolone has gained increasing attention due to its diverse pharmacological properties [4] such as cytotoxic [5,6], anti-inflammatory [7], antimicrobial [8,9], antioxidant [10], antiviral [11], oral hypoglycemic activity [12] and analgesic [13,14].…”