Devika Tripathi1*, Nandini Chaudhary1, Dinesh Kumar Sharma2, Jagannath Sahoo3
1Pharmacy Department, Pranveer Singh Institute of Technology, Kanpur, India.
2Pharmacy Department, Himalayan Institute of Pharmacy Dehradun, Uttarakhand, India.
3Pharmacy Department, Krishna Institute of Engineering and Technology, Ghaziabad, India.
Ketoprofen used as a Non-steroidal anti-inflammatory drug selected as a poorly water-soluble model drug. Due to the poorly soluble nature of Ketoprofen liberate reduced bioavailability. Hydrotropic solubilization technique is a promising technique used to improve the solubility of water-insoluble drugs. In this investigation, 2M sodium salicylate has been employed in the titrimetric estimation of Ketoprofen and shows synergistic enhancement in the solubility of Ketoprofen by many folds as compared to the distilled water. It excluded the use of various organic solvent like ethanol; methanol and chloroform widely utilized in the titrimetric estimation of various poorly soluble drugs but due to the higher cost, volatility, toxicities lead to environmental pollution hence are the cons of it. The proposed method is new, simple, precise, and inexpensive. The results of the analysis have been validated statistically. The mean % recoveries were found to be close to 100, indicating the accuracy of the proposed method. Low values of standard deviation, % coefficient of variation, and standard error further proved the reproducibility and precision of the proposed method.
Ketoprofen, Non-steroidal anti-inflammatory drugs. It is widely known to manage mild to moderate pain, fever, and inflammation narrowing the prostaglandin level, responsible for pain, fever, and inflammation. Responses can be projected by blocking the enzyme i.e. cyclooxygenase resulted out in subtracting the pain and fever1-10. It is known to exhibit poor water solvency and dissolubility. Reportedly, numerous techniques have been explored to boost up the solubility of such poorly soluble drugs. Among them, the Hydrotropic solubilization technique is found to be potent that accounts for enhancing the solubility of drugs with the involvement of the third component i.e. hydrotropes which is in charge of increasing the solubility of poorly soluble drugs.
There are various hydrotropic agents such as urea, sodium benzoate, sodium citrate, sodium salicylate, sodium acetate, etc. that have been employed to strengthen the aqueous solubility of drugs11-20. In this context, a hydrotropic solution of sodium salicylate was employed as a solubilizing agent to analyze the drug i.e. Ketoprofen through titrimetric estimation. The solubility of Ketoprofen in 2M sodium salicylate solution was utilized for the study. There was an enormous increase in solubility of Ketoprofen was observed. Continuance of study further employed various organic solvents like methanol, chloroform, alcohol, dimethylformamide, and benzene for the solubilization of poorly water-soluble drugs and their analytical studies were also the part of. Primarily, the objective of this study was to employ the concept of hydrotropy and preclude the use of organic solvents21 to overcome the existing drawbacks of organic solvents like higher cost, toxicity, pollution, and analytical errors due to volatility.30.
MATERIAL AND METHOD
Ketoprofen was supplied as a gift sample by Akums Drugs and Pharmaceutical Ltd. All other chemicals and solvents were used for an analytical grade.
Analysis of Ketoprofen bulk drug by IP:
For the analysis of Ketoprofen from official method Indian Pharmacopoeia31,32: Accurately weighed 100mg of Ketoprofen drug was dissolved in 25ml of ethanol (95%) which was previously neutralized to phenolphthalein solution which was used as an indicator, 25ml of water was also added. It was then titrated with a 0.1M sodium hydroxide solution. Each ml of 0.1M sodium hydroxide is equivalent to 0.02543g of C16H14O3. Drug content was determined (n=3) and represent in Table 1.
Analysis of Ketoprofen bulk drug by the proposed method:
In the proposed method for analysis: Weighed accurately approx.100mg of Ketoprofen drug and transferred to a 250ml conical flask. 25ml of a solution of 2 M sodium salicylate was added and the flask was shaken for about 10 min to dissolve the drug. Titration was performed with 0.1 M sodium hydroxide using phenolphthalein as an indicator. Blank titration was performed for necessary correction. Each ml of 0.1 M sodium hydroxide is equivalent to 0.02543 g of C16H14O3. Drug content was determined (n=3) and presented in Table 1.
Table 1: Analysis data of bulk drug sample with statistical evaluation (n= 3)
Amount of bulk Drug taken (mg)
Method of analysis
% drug estimated (Mean ± S.D.)
Coefficient of Variation (%)
IPM = Indian Pharmacopoeia method, PTM= Proposed titrimetric method
RESULT AND DISCUSSION:
From the above-mentioned table, the results demonstrate that the mean percent drug content of Ketoprofen in the bulk sample was measured by the Indian Pharmacopoeia method was 99.25±1.155 shown in table no. 1. Likely, the proposed method was successfully applied in the analysis of bulk drug, and the mean percent drug content of Ketoprofen reported was 98.97±1.033 employing 2M sodium salicylate. Hence, the obtained results revealed the accuracy of results between the analysis done by the proposed method and the analysis of the standard method i.e. Indian Pharmacopoeia, and proven that the proposed method productively enhanced the solubility of Ketoprofen in 2 M Sodium salicylate than in distilled water.
Hence, the proposed method proved to be simple, accurate, new, and environment friendly. The organic solvent is precluded but not at the expense of accuracy. The proposed method can be successfully employed in the routine analysis of Ketoprofen. There is a good scope for other poorly water-soluble drugs which may be tried to get solubilize by suitable hydrotropic agents to carry out their titrimetric analysis precluding the use of costlier and unsafe organic solvents. Like this method, other hydrotropes can also be tried by combining them to exert a synergistic effect on the solubility of poorly water-soluble drugs to be applied in different fields of analysis. Mixed hydrotropy may find wide use in the development of aqueous formulations of poorly water-soluble drugs in the future.
The authors are thankful to Akums drugs and Pharmaceuticals Ltd., Haridwar for supplying Ketoprofen as a gift sample.
CONFLICT OF INTEREST:
The authors declare no conflict of interest
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25. Maheshwari RK, Chaturvedi SC, Jain NK. Novel application of Hydrotropic Solubilization in the Quantitative analysis of some NSAIDs and their solid dosage forms. Indian Journal of Pharmaceutical Science. 2007; 69(1): 101-105.
26. Maheshwari RK, Gupta HM, Singh M, Ramchandani U, Pandey S.P. A novel application of Hydrotropic Solubilization in the Spectrophotometric analysis of Gatifloxacin in a solid dosage form. Asian Journal of Chemistry. 2008; 20(1): 241- 244.
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32. Darwish A, Florence AT, Saleh AM. Effects of hydrotropic agents on the Solubility, Precipitation, and protein binding of Etoposide. Journal of Pharmaceutical Science. 1989; 78: 577- 581.
Received on 04.05.2020 Modified on 15.06.2020
Accepted on 20.07.2020 © RJPT All right reserved