Development, Validation & Applications of Green UV Method for the Estimation of Ibuprofen in Solid Dispersion

Ibuprofen is a non-steroidal anti-inflammatory drug widely used for the treatment of pain, inflammation, and fever. It belongs to the propionic acid derivatives class of NSAIDs. Ibuprofen is classified as a Biopharmaceutics Classification System Class II drug because it has low aqueous solubility and high permeability. Its poor aqueous solubility can reduce dissolution rate and may affect oral drug availability.

Table No. 1. Physicochemical properties of Ibuprofen

Solid dispersion is an effective technique used to improve the solubility and dissolution rate of poorly water-soluble drugs. In this technique, the drug is dispersed in a hydrophilic carrier, which can improve wettability, reduce particle aggregation, increase surface area, and improve contact between the drug and dissolution medium. [1-6, 12, 15] Sodium starch glycolate was selected as the carrier in the present study because of its swelling property and ability to improve the wettability of poorly soluble drugs.

UV spectrophotometry is a simple, rapid, economical, and commonly used technique for estimation of drugs in pharmaceutical formulations. [7-9, 13, 14] Green analytical chemistry focuses on reducing the use of toxic solvents and minimizing environmental impact during analysis. Ethanol and water are comparatively safer, economical, and environmentally acceptable solvents. [10, 11] Therefore, ethanol: water in the ratio of 50:50 v/v was selected as a green solvent system for the estimation of Ibuprofen.

The present study was carried out to develop a UV spectrophotometric method for Ibuprofen using ethanol: water (50:50 v/v), validate selected analytical parameters, prepare ibuprofen solid dispersion using sodium starch glycolate by solvent evaporation method, and evaluate the solubility enhancement of the prepared formulation.

2. MATERIALS AND METHODS

1. 1. Materials

Ibuprofen active pharmaceutical ingredient was used as the model drug. Sodium starch glycolate was used as the hydrophilic carrier for preparation of solid dispersion. Ethanol and distilled water were used for preparation of ethanol: water solvent system in the ratio of 50:50 v/v. Marketed ibuprofen tablets were used for comparative solubility study.

1. 2. Instruments

A UV-Visible spectrophotometer was used for absorbance measurement. Other instruments used were a sonicator, hot air oven, digital weighing balance, centrifuge, volumetric flasks, pipettes, glass rod, and other standard laboratory glassware.

1. 3. Preliminary Solubility Study

The solubility of ibuprofen API was studied in distilled water, ethanol, and ethanol: water (50/50 v/v). An accurately weighed quantity of ibuprofen API was added to each solvent system and mixed properly. The solubility behaviour was observed, and ethanol: water (50/50 v/v) was selected for further analytical and formulation studies because it showed suitable solubility and supported green chemistry principles.

1. 4. Determination of λ_max

A standard solution of Ibuprofen was prepared using ethanol: water (50/50 v/v). The solution was scanned over the wavelength range of 200-400 nm using ethanol: water (50/50 v/v) as blank. The wavelength at which maximum absorbance was obtained was selected as the λ_max for further analysis.

1. 5. Preparation of Calibration Curve

A standard stock solution of Ibuprofen was prepared in ethanol: water (50:50, v/v). Suitable dilutions were prepared to obtain concentrations of 3, 6, 9, 12, and 15 μg/ml. The absorbance of each solution was measured at 222nm. A calibration curve was plotted between concentration and absorbance, and the regression equation and coefficient of determination were calculated.

1. 6.  Method Validation

The developed UV spectrophotometric method was evaluated for linearity, accuracy, precision, robustness, ruggedness, limit of detection, and limit of quantification.

Linearity was evaluated using Ibuprofen concentrations of 3-15 μg/ml. Accuracy was evaluated by recovery study at 80%, 100%, 120% levels. System precision was determined by repeated measurement of Ibuprofen standard solution. Intra-day and inter-day precision were determined by analysing Ibuprofen solution at different concentrations within the same day and on different days, respectively.

Robustness was evaluated by making small changes in wavelength from 222 nm to 220 nm and 224 nm. Ruggedness was evaluated by performing the analysis using two different analysts. LOD and LOQ were calculated from the standard error and slope of the calibration curve. [8, 9]

1. 7. Preparation of Solid Dispersion

Ibuprofen solid dispersion was prepared by solvent evaporation method using sodium starch glycolate as hydrophilic carrier in a drug-to-carrier ratio of 1:2. Accurately weighed Ibuprofen API and sodium starch glycolate were transferred into a clean beaker. Ethanol: water (50:50 v/v) solvent system was added to dissolve the drug and uniformly disperse the carrier.

The mixture was sonicated to obtain a homogeneous dispersion. The solvent was evaporated, and the obtained mass was dried in a hot air oven until complete removal of solvent. The dried mass was triturated gently, passed through sieve no. 44, and stored in an airtight container for further evaluation. [1-6]

1. 8. Drug Content Analysis

An accurately weighed quantity of prepared solid dispersion equivalent to the required amount of Ibuprofen was transferred into a volumetric flask containing ethanol: water (50:50 v/v). The solution was sonicated to ensure dissolution. Suitable dilution was prepared, and absorbance was measured at 222 nm. Drug content was calculated using the calibration curve equation.

1. 9. Solubility Enhancement Study

The solubility enhancement study was performed to compare Ibuprofen tablet powder and prepared Ibuprofen solid dispersion. Accurately weighed quantities of Ibuprofen tablet powder and solid dispersion were separately dispersed in the selected solvent system. The samples were kept for 24 and 48 hours. After equilibration, the samples were centrifuged, and the supernatant was collected. Suitable dilutions were prepared from the supernatant, and absorbance was measured at 222 nm using a UV-Visible spectrophotometer.

2.10 STATISTICAL ANALYSIS

The results were expressed as mean, standard deviation, and percentage relative standard deviation. The calibration curve was evaluated by linear regression analysis, and the coefficient of determination was calculated.

Table No.2. Solubility study of Ibuprofen API

3. RESULTS AND DISCUSSION

1. 1. Preliminary Solubility Study

Ibuprofen showed low solubility in distilled water and high solubility in ethanol. Ethanol: water (50:50 v/v) showed suitable solubility and was therefore selected for further analytical and formulation studies. The selected solvent system was also considered comparatively safer and suitable for a green analytical approach.

 3.2 Green Chemistry

Fig No. 1. Green Chemistry Assessment of the Developed UV Spectrophotometric Method

The developed UV spectrophotometric method achieved a green chemistry score of 0.75 indicating good compliance with the principles of Green Analytical Chemistry. The use of an Ethanol: water (50:50 v/v) solvent system reduced the use of hazardous organic solvents and minimized environmental impact. The method required comparatively low solvent consumption, generated less hazardous waste, and involved simple analytical instrumentation with low energy requirements. These findings demonstrate that the developed method is environmentally friendly and suitable for routine pharmaceutical analysis while supporting sustainable analytical practices.

1. 3. Determination of λ_max

Table No. 3. Determination of λ_max of Ibuprofen

The UV spectrum of Ibuprofen showed maximum absorbance at 222 nm in ethanol: water (50:50 v/v). Therefore, 222 nm was selected as the λ_max for further analysis.

Fig. No. 2. Lambda max (λ_max) of Ibuprofen

Table No. 4. Calibration Curve of Ibuprofen

Sr. No.	Concentration (μg/ml)	Absorbance	Mean	Standard Deviation	% Relative Standard Deviation
1.	1.1 μg/ml	0.148	6.98	4.746788	0.680056
2.	4.0 μg/ml	0.351
3.	6.8 μg/ml	0.548
4.	9.8 μg/ml	0.757
5.	13.2 μg/ml	0.992

Fig. No. 3. Calibration Curve of Ibuprofen

Fig No. 4. Overlay Graph of Calibration Curve

The solubility study showed that the Ibuprofen solid dispersion had higher absorbance than Ibuprofen tablet powder after 24 hours and 48 hours. At 24 hours, the solid dispersion show an absorbance of 0.792 compared with 0.267 for tablet powder. At 48 hours, the solid dispersion showed an absorbance of 0.839 compared with 0.298 for tablet powder. These findings indicate improved solubility of Ibuprofen in the prepared solid dispersion.

The enhanced solubility may be due to improved wettability, reduced aggregation of drug particles, and increased surface area of Ibuprofen in the presence of sodium starch glycolate. The hydrophilic carrier may have helped the drug particles to disperse more effectively in the solvent system. 

4. CONCLUSION

A green UV spectrophotometric method was developed for estimation of Ibuprofen using ethanol: water (50:50, v/v) as solvent system. Ibuprofen showed maximum absorbance at 222 nm, and the method was linear in the concentration range of 3-15 μg/ml with an R² value of 0.9988. The method showed acceptable precision, robustness, ruggedness, LOD, and LOQ under the studied conditions. Ibuprofen solid dispersion prepared using sodium starch glycolate in a 1:2 drug-to-carrier ratio showed improved solubility compared with ibuprofen tablet powder.

The accuracy and drug-content findings indicate that further optimization of sample preparation, dilution, and calculation procedures is required before the method can be claimed as fully validated for routine quality-control analysis. However, the study demonstrated the potential of solid dispersion technology and ethanol: water (50:50, v/v) solvent system for improving the solubility and analytical estimation of ibuprofen

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