Vivekkumar K Redasani, Omkar C. Bhalerao, Mohan G. Kalaskar, Sanjay J. Surana
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.
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Ramesh Jayaprakash, Senthil Kumar Natesan
A simple, economic, accurate, sensitive, specific and precise stability indicating reverse phase high performance liquid chromatographic [RP-HPLC] method for the determination of Regorafenib in pure and tablet dosage from was developed and validated. The chromatographic separation was carried out using Phenomenex Luna-C 18 column (4.5x250 mm; 5 µm particle size) as a stationary phase and methanol: acetonitrile: water (55:25:20 v/v/v) as a mobile phase. The flow rate of 1 mL/min was used with PDA detection at 275 nm. The retention time of Regorafenib was 2.480 min. RP-HPLC method was developed with linearity range of 40-240 µg/mL of Regorafenib. The correlation coefficient [r 2 ] was found to be 0.9999. The assay results obtained was in good agreement with the corresponding labeled amount by developed method within range of 98.83 ± 0.6937. Accuracy of the method was confirmed by recovery studies and the recoveries were found to be between 99.61 % and 100.22 %, the corresponding %RSD was found to be 0.2029. Precision, LOD, LOQ, specificity, robustness and ruggedness were performed as per ICH Q2(R1) guidelines and were within the acceptance criteria. This method can be conveniently used to detect the possible degradation product in the dosage form of Regorafenib during stability studies (acidic, alkaline, oxidative, thermal and photolytic). The method proved to be effective on the analysis of stressed marketed tablet formulation.
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