1Daly College ,1, Residency Area, Indore, Madhya Pradesh 452001 (M.P.)
2Department of Pharmacy, Shri G.S. Institute of Technology and Science, 23, Park Road Indore (M.P.) 452003.
In the present investigation, ibuprofen, a commonly used non-steroidal anti-inflammatory drug (NSAID), was selected as a model compound to explore solubility enhancement through the hydrotropy technique. A synergistic blend of hydrotropic agents comprising 15% sodium salicylate, 5% niacinamide, 5% sodium citrate, and 5% sodium acetate was employed for this purpose. The mixed hydrotropic system demonstrated a remarkable increase in solubility, exhibiting more than a forty-fold enhancement compared to the solubility of ibuprofen in distilled water. This significant improvement confirms the potential of hydrotropic combinations as an efficient and environmentally safer alternative to conventional solubilization methods. Furthermore, the hydrotropy assisted solubilization was effectively utilized in the titrimetric estimation of ibuprofen, eliminating the requirement for organic solvents that are often hazardous, expensive, and environmentally unfriendly. The analytical results obtained using the proposed method were in excellent agreement with those reported in the Indian Pharmacopoeia, confirming the accuracy and reliability of the developed approach. Importantly, the presence of the hydrotropic agents did not interfere with the analytical procedure, ensuring the precision of the estimation. Overall, the study demonstrates that the mixed hydrotropic system provides a simple, safe, economical, and eco-friendly method for enhancing the solubility and analytical determination of poorly water-soluble drugs like ibuprofen, potentially extending its application to other BCS Class II drugs.
Ibuprofen is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) due to its analgesic, antipyretic, and anti-inflammatory effect[1]. Despite its therapeutic benefits, ibuprofen’s poor solubility,[2] in water poses challenges for both formulation development and accurate analytical estimation. Traditional methods to improve solubility often rely on organic solvents such as methanol, ethanol, chloroform, or acetone However, these solvents are associated with several disadvantages, including toxicity, high cost, and environmental concerns[3]. In response to these issues, the field of green analytical chemistry has gained importance, emphasizing safer, more sustainable methods that minimize or eliminate the use of hazardous chemicals[4].
Hydrotropy[5] has emerged as a promising strategy to enhance the solubility of poorly water-soluble drugs.[6] This approach involves the use of hydrotropic agents[7], which are typically organic salts or compounds capable of increasing solubility through molecular interactions without altering the chemical structure of the drug[8]. The concept of mixed hydrotropy [9-11] where multiple hydrotropic agents are combined, has shown a synergistic effect[12], further improving solubility[13] while reducing the quantity of individual agents required[6].
Titrimetric analysis provides a straightforward and cost-effective method for quantitatively determining the purity and content of the active pharmaceutical ingredient Ibuprofen[14], [15, 16]. The process involves dissolving a precisely weighed sample of powdered Ibuprofen tablets in a neutral, organic solvent like ethanol or methanol, since Ibuprofen is largely insoluble in water[17].
In this study, ibuprofen was chosen as a model drug to investigate solubility enhancement and quantitative determination using a mixed hydrotropic system[11, 18, 19]. The goal is to develop a simple, cost-effective, and environmentally friendly analytical method[18] that avoids the use of toxic organic solvents[18], thereby aligning with green chemistry principles and promoting sustainable practices in pharmaceutical analysis[8, 20-23].
MATERIALS AND METHODS
MATERIALS
Ibuprofen drug sample and solvents employed in this analysis were taken for analysis from Schon Pharmaceutical Limited, Indore.
METHOD
Preparation Of Mixed Hydrotropic Solution
15 g of Sodium Salicylate, 5 g of Niacinamide, 5 g of Sodium Citrate and 5 g of Sodium Acetate were transferred in a 100 ml volumetric flask and about 60 ml of the distilled water was added. Flask was shaken sufficiently to get clear solution, then volume was made up to 100 ml with distilled water to get the mixed hydrotropic blend.
Solubility Studies of Ibuprofen
The solubility of Ibuprofen in the hydrotropic blend was determined at 28 ± 1 °C. An excess amount of ibuprofen was added to a screw-capped 30 mL glass vial containing the mixed hydrotropic blend solution. The vial was mechanically shaken for 12 hours at 28 ± 1 °C in an orbital flask shaker (Khera Instruments Pvt. Ltd., Indore). After sealing the vial with a rubber closure and an aluminium cap to ensure an airtight fit, it was kept undisturbed for 24 hours. The solution was then centrifuged for 5 minutes at 2000 rpm (Remi, India). The supernatant liquid was filtered through Whatman filter paper No. 41, and the filtrate was analysed titrimetrically to determine the solubility[24].
Analysis Of Ibuprofen Drug Sample by Indian Pharmacopoeial Method
400 mg Ibuprofen drug was weighed accurately and transferred in a conical flask. 100 ml of ethanol (95%) was taken in another conical flask and few drops of phenolphthalein indicator were added. Clear colourless solutions was obtained. Then 0.1N NaOH solution was added one drop at a time and flak was shaken. Addition of 0.1 N NaoH was continued to get just pink colour. Now, this is phenolphthalein neutralized ethanol. Then this ethanol was transferred to conical flask containing the Ibuprofen drug and flask was shaken to get clear solution. Then titration was perform adding the 0.1 N NaOH from burette. Same procedure was repeated two times more[25].
Analysis Of Ibuprofen Drug by Proposed Method Using Mixed Hydrotropic Blend Solution.
100 ml of mixed hydrotropic blend solution was transferred in a conical flask and few drops of phenolphthalein indicator solution were added remained colourless . Drop by drop 0.1 N NaOH was added to get just pink colour. Then , 400 mg ibuprofen drug sample was transferred in the conical flask and the flask was shaken to get clear solution . Then, titration was performed adding 0.1 N NaOH from burette same procedure was repeated two more times.
RESULT AND DISCUSSION
Percent drug estimation by the proposed method was found to be 97.48 and 98.56% by Indian Pharmacopeial method. Result from the solubility studies as evident from experiment showed that enhancement in solubility by utilization of ibuprofen by more than 40-fold. And the results from the proposed analysis method are comparable with the Indian pharmacopoeia method. The validation of proposed method is further confirmed statically by low values of standard deviation percent coefficient of variation and standard error.
Table 1- Analysis Data of Ibuprofen Bulk Drug Sample
|
Amount Of Drug Taken (Mg) |
Amount Found (Mg) |
Percentage Estimated |
||
|
|
IPM |
PM |
IPM |
PM |
|
400 mg |
390.62 |
389.21 |
97.66 |
97.48 |
|
400 mg |
393.57 |
399.92 |
98.39 |
99.80 |
|
400 mg |
398.77 |
394.76 |
99.69 |
98.69 |
Table 2 – Statistical Evaluation of Analysis
|
Method |
Mean Percent Estimated |
Standard Deviation |
% Cofficient Of Variation |
Standard Error |
|
IPM |
98.56 |
1.0285 |
1.043 |
0.593 |
|
PM |
98.66 |
1.1603 |
1.118 |
0.662 |
CONCLUSION
The present work establishes that hydrotropic agents can serve as reliable and environmentally friendly substitute for conventional methods in the titrimetric estimation of ibuprofen. By significantly improving the solubility of ibuprofen in aqueous medium and eliminating the dependence on organic solvents, the hydrotropic technique provides a straightforward, precise, and economical option for routine pharmaceutical analysis. Definitely there is further scope of hydrotropic solubilizing agent for titrimetric analysis of ibuprofen without the use of organic solvents.
REFERENCES
T. Motwani*, A. Mali, Green and Efficient Estimation of Ibuprofen Via Mixed Hydrotropy Approach, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 4186-4190 https://doi.org/10.5281/zenodo.17723506
10.5281/zenodo.17723506
