Lornoxicam is a selective cyclooxygenase-1 and cyclooxygenase-2 inhibitor that exhibits anti-inflammatory, analgesic, and antipyretic activities. It is used in osteoarthritis and rheumatoid arthritis; and in treatment of postoperative pain and primary dysmenorrhoea. Lornoxicam is completely insoluble in water but soluble in alkaline solutions. Hydrotropic solubilization is a technique used to increase the aqueous solubility of poorly water-soluble drugs and the present study was aimed at developing a hydrotropic technique to increase the solubility of lornoxicam, using 2 M sodium benzoate as the hydrotropic agent. Beer’s law was obeyed in the concentration range of 4–24
Various techniques have been employed to enhance the aqueous solubility of poorly water-soluble drugs. Hydrotropic solubilization is one such method [
Lornoxicam, an oxicam derivative, is a nonsteroidal anti-inflammatory drug, is a selective cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) inhibitor, and exhibits anti-inflammatory, analgesic, and antipyretic activities. It is used in muscular, skeletal, and joint disorders such as osteoarthritis and rheumatoid arthritis. It is also used in the treatment of other painful conditions including postoperative pain and primary dysmenorrhoea.
Lornoxicam is practically insoluble in water but soluble in alkaline solutions. Most of the previous methods employed have used organic solvents or hydrotropes such as sodium lauryl sulphate and urea to increase aqueous solubility of lornoxicam [
UV/visible spectrophotometer (Model-UV-1700, Shimadzu, Japan) was employed for the spectral measurements. Lornoxicam was a generous gift sample from Life Care Formulations Pvt. Ltd., Pondicherry. Commercial tablets of lornoxicam (LORSAID 4, Abbott Healthcare Pvt. Ltd., Mumbai) were purchased from the local pharmacy. All other chemicals and solvents used were of analytical grade.
Solubility of lornoxicam was determined by saturation aqueous solubility method in 2 M sodium benzoate. An excess amount of drug was added to the 100 mL beakers containing mixture of 2 M sodium benzoate. The beakers were shaken for 12 hours at
The standard stock solution of lornoxicam was prepared by dissolving 50 mg of drug in 50 mL of 2 M sodium benzoate. From this stock solution 5 mL was diluted to 50 mL with distilled water to get a concentration of 100
UV spectrum of lornoxicam in 2 M sodium benzoate as hydrotropic agent.
From the stock solution, serial dilutions were made and the absorbances of solutions were measured at the respective wavelength as per the developed method to confirm the linearity.
In order to check the accuracy and reproducibility of the proposed method, recovery studies were conducted. Tablet powder (commercial formulation) equivalent to 4 mg of lornoxicam was transferred to a 50 mL volumetric flask containing 40 mL of 2 M sodium benzoate. Pure lornoxicam sample (2 mg) was added to the same volumetric flask. The flask was shaken for 5 min to solubilize the drug. The solution was then filtered through Whatman filter paper No. 41. The filtrate was diluted with distilled water appropriately and absorbance was measured at 381 nm against corresponding reagent blank. Drug content was estimated and percent recovery was calculated using the following formula. Similar procedure was repeated using 4 mg and 6 mg of pure lornoxicam as spiked concentration. Consider
Precision was determined by studying the repeatability and intermediate precision. The standard deviation, coefficient of variance (CV), and standard error were calculated for the drug.
The intraday concentration of the drug was calculated on the same day at an interval of one hour, whereas the interday concentration of drug was calculated on three different days, within the laboratory conditions [
The intersubject variation was calculated by taking into account the analysis carried out by three different individuals on the same day and at the same time, within the laboratory conditions [
The LOD and LOQ of lornoxicam by the proposed method were determined using calibration standards. LOD and LOQ were calculated as
The results of solubility studies indicated that aqueous solubility of lornoxicam was enhanced in hydrotropic mixture solution of 2 M sodium benzoate as compared to solubility in distilled water. The solubility of pure lornoxicam in distilled water was found to be 0.012 mg/mL, whereas in 2 M sodium benzoate the solubility was found to be approximately 5 mg/mL. The increase in solubility was more than 100-fold. Hence this method was optimized and employed in the analysis of the tablet formulation. A portion of the solution was kept at room temperature for 24 hours to check the stability of drug in presence of sodium benzoate.
The study revealed that estimations of lornoxicam can be done within 24 hours without any detrimental effect on drug stability as no precipitation was observed. From this study it is obvious that there was no interference of 2 M sodium benzoate in estimation of lornoxicam at the wavelength of 381 nm. Based on this a large number of poorly water-soluble drugs having
The Beer-Lambert’s concentration range was found to be 4–24
Analysis of tablet formulations of lornoxicam.
Tablet formulation | Label claim |
% label claim |
Standard error |
---|---|---|---|
Commercial tablet I | 4 | 100.03 ± 0.217 | 0.1087 |
Accuracy and reproducibility of the proposed method were further confirmed by recovery studies. The results of the study revealed that any small change in the drug concentration in the solution could be accurately determined by the proposed method (Table
Result of recovery studies.
Amount of |
Amount of |
% recovery |
Standard error |
---|---|---|---|
4 | 2 | 100.17 ± 0.431 | 0.216 |
4 | 4 | 100.21 ± 0.205 | 0.102 |
4 | 6 | 99.99 ± 0.013 | 0.006 |
Repeatability results indicated the precision under the same operating conditions over a short interval of time and interassay precision. Intermediate precision study expresses variation within laboratory conditions in different days.
In intra- and interday precision and intersubject variation study, coefficient of variation was not more than 1.0% indicating good intermediate precision.
The value of LOD was 0.34
Optical characteristics data and validation parameters.
Parameters | Values for lornoxicam |
---|---|
Working |
381 nm |
Beer’s law limit | 4–24 |
Molar absorptivity | 14.537 |
Correlation coefficient* | 0.9998 |
Intercept* | 0.0032 |
Slope* | 0.03873 |
LOD* | 0.34 |
LOQ* | 1.038 |
Intraday precision* (CV) | 0.0071 |
Interday precision* (CV) | 0.0012 |
Intersubject precision* (CV) | 0.0046 |
Thus a new method has been developed that is precise, simple, cost effective, accurate, and safe which has been validated. This proposed method which was developed on the principle of hydrotropic solubilization concept can be well employed in routine analysis of lornoxicam in tablets.
The authors report no conflict of interests.
The authors are thankful for Gokula Education Foundation for providing necessary facilities to carry out the research work.