Synthesis and evaluation of novel mutual prodrugs of Piroxicam

Abstract

Therapeutic efficacy of piroxicam can be improved by retarding gastrointestinal side effects by means of temporarily modification of enolic hydroxyl group chemically. The NSAIDs such as aceclofenac, ibuprofen, mefenamic acid and naproxen were selected as promoities with the aim of getting synergistic effect through these well known pharmaco-counter parts. The targeted prodrugs are synthesized successfully and confirmed by characterization. Synthesis involved chlorination of NSAIDs and coupling of this acid chloride with piroxicam through enolic hydroxyl group to get ester derivatives. Mutual prodrugs were evaluated by hydrolysis study at different pH (acidic, neutral, alkaline) using phosphate buffer. Prodrug derivatives were found to be stable at acidic and neutral pH but prone to hydrolysis at alkaline pH. Thus the objective of the presented study was to overcome the undesirable side effects of NSAIDs. Thus, current studies confirms that the mutual prodrug approach can be applied effectively in order to achieve the purpose of raising effectiveness of piroxicam under two lines; firstly, masking of enolic hydroxyl group through acids and converting them to esters and secondly, utilizing the known NSAIDs for achieving the synergistic effect.

Mutual Prodrugs of Piroxicam

“…This is due to local effect applied by direct contact of drug with gastric mucosa [3]. The enolic hydroxyl group of piroxicam and free acidic group of aryl propionic acids plays a key role in sustaining the efficiency and making the gastric ulceration as well [4].…”

A comparative study of different electrodeposited NiCo2O4 microspheres anchored on a reduced graphene oxide platform: electrochemical sensor for anti-depressant drug venlafaxine

“…Also, thin layer chromatography (TLC) was described for VEN analysis in bulk and capsules. 13 Many spectrophotometric methods [14][15][16][17][18][19][20][21][22] and spectrouorimetric methods 23,24 have been reported for quantitation of VEN as well. Capillary electrophoresis was used for stereoselective analysis of VEN and its metabolites 25 and for determination of the toxic levels of VEN in human serum.…”