Stability Indicating

A simple and precise stability-indicating high performance liquid chromatography method was developed and validated for the simultaneous estimation of Tolperisone Hydrochloride and Diclofenac Sodium in commercial tablet dosage form. Separation was achieved by using C18 (250mm × 4.6 mm, 5µm) column and mobile phase comprising of potassium dihydrogen phosphate buffer (pH: 6.0): acetonitrile (70:30% v/v) at a flow rate of 1.0ml/min. The detection wavelength was 275 nm. The retention times for Tolperisone Hydrochloride and Diclofenac Sodium were 5.26min and 3.59min, respectively. Linearity of Tolperisone Hydrochloride and Diclofenac Sodium were found in range of 15-52.5µg/ml and 5-17.5µg/ml. The % recovery of Tolperisone Hydrochloride was found to be 99.58%-100.88% and 100.75%-101.33% for Diclofenac Sodium. The values of Limit of detection and limit of quantification were found to be 0.203µg/ml and 0.616µg/ml for Tolperisone Hydrochloride and 0.003µg/ml and 0.010µg/ml for Diclofenac Sodium, respectively. The linear regression coefficient for both drugs was found to be 0.999. The method was found to be robust since the retention times and areas were within the limits even after little deliberate variations in pH, flow rate, mobile phase ratio. Stress studies were conducted on the drug substance and product under the ICH prescribed stress condition viz. hydrolysis, oxidation, photolysis and thermal stress. The drugs showed sufficient decomposition under acidic hydrolysis, alkaline hydrolysis, and oxidation. The drug was found to be moderately sensitive to thermal studies and sunlight studies. This method can be successfully employed for simultaneous quantitative analysis of Tolperisone Hydrochloride and Diclofenac Sodium in pharmaceutical dosage form.

A simple, rapid, accurate, precise and economical reverse phase high performance liquid chromatographic method was developed for simultaneous quantification of two anti-hypertensive drugs Olmesartan and Chlorthalidone. The separation of both the drugs was achieved on BDS C18 250mm x 4.6 mm, 5m using a mobile phase of 10 mM orthophosphoric acid buffer and acetonitrile (45:55v/v) at a flow rate of 1.0 mL min-1 and detection was performed at 212 nm using photodiode array (PDA) detector. The drug was subjected to various ICH prescribed stress conditions including hydrolysis (neutral, acid and alkaline), oxidation, photolysis and thermal degradation. The proposed method was validated with respect to specificity, linearity, accuracy, and precision, limit of detection (LOD), limit of quantitation (LOQ), stability and robustness as per ICH guidelines. The proposed analytical method could effectively separate the drug from its degradation products employed as stability indicating studies.

The concept of "Quality by Design" (QbD) is getting popularized in pharmaceutical manufacturing industry to understand the product and process to identify the risks involved during manufacturing.  One of the perpetual quality attribute is to have robust analytical method that can provide consistent results though out the life cycle of the product. General considerations during analytical method validation is to perform robustness studies by deliberate changes made in pH of the buffer in mobile phase, change in organic ratio, change in column oven temperature, change in buffer strength and using different column lot numbers etc. However to improve the analytical quality standard, a novel method concept under QbD was introduced which uses single mobile phase for three drug components and estimates using different column chemistries used in pharmaceutical industry viz., C18, C8, phenyl and Cyano column. The validated RP-LC method was successfully applied to the quantitative determination of Chlorpheniramine, Ibuprofen and Pseudoephedrine in tablet dosage form, helping to improve quality control and to assure therapeutic efficacy using all column chemistries.

  The present work describes the development of stability indicating assay method for Diacerein and Aceclofenac in their combined dosage form that would provide helpful information to the manufacturers. Stress studies were conducted on the drug substance and product under the ICH prescribed stress conditions viz. hydrolysis, oxidation, humidity, photolysis, thermal stress. The separation of the drug from its degradation products, trials were made by taking acetonitrile: water, acetonitrile: phosphate buffer, acetonitrile: phosphoric acid in various blends. Separation was achieved using C-18 column and a mobile phase comprising of Acetonitrile: Phosphoric acid 0.1 M (61: 39) at a flow rate of 1.5 mL/min. The detection wavelength was 260 nm. The drug showed sufficient decomposition under alkaline hydrolysis (0.05 N NaOH), acidic hydrolysis (0.05 N HCl), neutral hydrolysis (distilled water), and oxidative hydrolysis (6% H2O2). The drug was found to be moderately sensitive to humidity studies (75 % RH), photochemical studies (UV 254 nm), and thermal studies (600C). Recovery studies were also carried out for both the drugs and the mean percent recovery were found to be 100.69 for diacerein and 99.15 for aceclofenac. Mean percent estimation in marketed formulation gave 99.63% for diacerein and 100.04% for aceclofenac. The above method was validated for accuracy, precision, ruggedness, limit of detection, limit of quantitation and was found to be satisfactory for routine analysis of diacerein and aceclofenac in their combined dosage form in the presence of their degradation products.   Key words: Aceclofenac, Diacerein, Stress Degradation, Stability Indicating, Validation