Forced Degradation
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A. J. Giri ◽  
Anjali D Kingre ◽  
J. K. Dhumal ◽  
P. R. Doifode ◽  
Pratiksha Jaybhaye ◽  

In present study, Accouring to specification of Indian pharmacopeia the content official limit of not less than (98.5%) and not more than (101.0%) of the lable amount our hypothesis was that when all different brands of metformin were expose to the different degradation parameters. The Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. A forced degradation study is an essential step in the design of a regulatory compliant stability program for both drug substances and products, and formalized as a regulatory requirement in ICH Guideline Q1A in 1993. Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions.

Kalyani Peluri ◽  
S. Rajasekaran

Aim: The foremost purpose of this research work is to diminish the analysis time and to establish cost effective method for estimation of Vildagliptin by RP-UPLC. Study Design: UPLC based Quantification studies. Place and Duration of Study: Department of Pharmacy, Bhagwant University, Ajmer, Rajasthan, Indiabetween June 2020 and August 2020. Methodology: A simple, responsive and precised RP-UPLC method with good robustness was developed and validated as per ICH for the analysis of Vildagliptin in drug substance and separation of degradants generated by different forced degradation conditions. Productive separation of Vildagliptin was attained by the use of Luna C18 column (100x2.6mm and 1.6µm) with a mobile phase composition of 0.1% v/v Trifluoroacetic acid and Acetonitrile in 80:20 v/v, which was pumped with 0.5 ml/min flow rate. The eluted substances were examined with PDA detector at 239nm. Stressed degradation studies were performed with proposed method to determine the percentage degradation of Vildagliptin. Results: The RT of Vildagliptin was observed at 1.56 min. The developed method was validated as per ICHQ2B and proved that the method was precise, sensitive, specific and accurate.The lowest concentration of limit of detection (0.05µg/ml) and limit of quantification(0.5µg/ml) of Vildagliptin make obvious about the sensitivity of the method. The correlation coefficient found to be 0.9997 for given range of linear concentrations. The calculated average percentage recoveries of Vildagliptin in spiked solutions were found to be in the range of 99.1-100.5. The calculated % RSD was determined to be less than 2. Determination of degradation of amount of Vildagliptin by forced degradation studies representing the stability indicating nature of the proposed method. Conclusion: The developed method said to be highly sensitive, accurate, specific and robust, therefore this method has high probability to adopt in pharmaceutical industry for regular analysis of Vildagliptin.

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5632
Anna Gumieniczek ◽  
Anna Berecka-Rycerz ◽  
Emilia Fornal ◽  
Barbara Żyżyńska-Granica ◽  
Sebastian Granica

During forced degradation, the intrinsic stability of active pharmaceutical ingredients (APIs) could be determined and possible impurities that would occur during the shelf life of the drug substance or the drug product could be estimated. Vildagliptin belongs to relatively new oral antidiabetic drugs named gliptins, inhibiting dipeptidyl peptidase 4 (DPP-4) and prolonging the activities of the endogenous incretin hormones. At the same time, some gliptins were shown as prone to degradation under specific pH and temperature conditions, as well as in the presence of some reactive excipients. Thus, forced degradation of vildagliptin was performed at high temperature in extreme pH and oxidative conditions. Then, selective LC-UV was used for quantitative determination of non-degraded vildagliptin in the presence of its degradation products and for degradation kinetics. Finally, identification of degradation products of vildagliptin was performed using an UHPLC-DAD-MS with positive ESI. Stability of vildagliptin was also examined in the presence of pharmaceutical excipients, using mid-IR and NIR with principal component analysis (PCA). At 70 °C almost complete disintegration of vildagliptin occurred in acidic, basic, and oxidative media. What is more, high degradation of vildagliptin following the pseudo first-order kinetics was observed at room temperature with calculated k values 4.76 × 10−4 s−1, 3.11 × 10−4 s−1, and 1.73 × 10−4 s−1 for oxidative, basic and acidic conditions, respectively. Next, new degradation products of vildagliptin were detected using UHPLC-DAD-MS and their molecular structures were proposed. Three degradants were formed under basic and acidic conditions, and were identified as [(3-hydroxytricyclo- [,7]decan-1-yl)amino]acetic acid, 1-{[(3-hydroxytricyclo[,7]decan-1-yl)amino]acetyl}-pyrrolidine-2-carboxylic acid and its O-methyl ester. The fourth degradant was formed in basic, acidic, and oxidative conditions, and was identified as 1-{[(3-hydroxytricyclo[,7]-decan-1-yl)amino]acetyl}pyrrolidine-2-carboxamide. When stability of vildagliptin was examined in the presence of four excipients under high temperature and humidity, a visible impact of lactose, mannitol, magnesium stearate, and polyvinylpirrolidone was observed, affecting-NH- and CO groups of the drug. The obtained results (kinetic parameters, interactions with excipients) may serve pharmaceutical industry to prevent chemical changes in final pharmaceutical products containing vildagliptin. Other results (e.g., identification of new degradation products) may serve as a starting point for qualifying new degradants of vildagliptin as it is related to substances in pharmacopoeias.

Khushboo Patel ◽  
Ujashkumar Shah ◽  
Hirak Joshi ◽  
Jayvadan K. Patel ◽  
Tejas B. Patel

Aims: The present research was aimed to develop and validate a reverse phase high performance liquid chromatographic (RP-HPLC) method for the quantification of Emtricitabine (EMT) and Tenofovir Alafenamide (TEN) in combination. Methodology: Separation was achieved under optimized chromatographic condition on an Inertsil C18, 250 x 4.6 mm, 5μm column. Various composition of mobile phase was tried. Separation of EMT and TEN was started with Methanol: Buffer and Methanol finally using solvent system of Buffer (pH 3.5) and Methanol in ratio of (30:70) and flow rate adjust at 1.0 ml/min was used as solvent system, the detection was carried out at 262nm using Shimazdu UV-visible detector. The mobile phase run time for the developed analytical method was 10 minutes. Results: The standard curve was found linear in the concentration range of 20-60 μg/ ml (r2- 0.9994) and 2.5-7.5 μg/ ml (r2-0.9992) for EMT and TEN respectively. The %RSD was found to be 0.80-0.95% and 0.63-1.09 for EMT and TEN respectively. Percentage (%) recoveries for EMT and TEN to be in range of 100%-100.6% and 99.32%-100.83% respectively. The limit of detection and the limit of quantification were found to be 4.80 μg/ ml and 14.7 μg/ ml respectively for EMT and 0.11 μg/ ml and 0.33μg/ ml respectively for TEN. Results of forced degradation study showed EMT degradation in acid and base medium while TEN was showed degradation in oxidative stress. The proposed developed RP-HPLC method was validated statistically and the values were found to be within the acceptable limits. Conclusion: In conclusion, the developed RP-HPLC method was found to be simple, specific, and rugged for simultaneous estimation of EMT and TEN. Validation results of method was found within the acceptable limits. Hence it can be used for analysis of EMT and TEN.

Patel Seema A. ◽  
Sayyed Nazifa S. ◽  
Lajporiya Mobina I. ◽  
Manjra Mehfuza U. ◽  
Aejaz Ahmed ◽  

Aims: To develop and validate a new, simple, rapid, precise, and accurate An Eco-friendly RP-HPLC and UV-Method Development and Validation for an estimation of Tolvaptan in Bulk and Tablet dosage form followed by Forced Degradation Studies Place and Duration of the Study: The present work has been carried out at Ali-Allana College of Pharmacy, Akkalkuwa between November-2020 to April-2021. Methodology: The UV-Spectroscopic method was developed for the estimation of tolvaptan in bulk and tablet dosage form. The solvent selected for the tolvaptan UV analysis was 4% aq. SLS solution, the solution of 10µg/ml was scanned in UV region from 200-400 nm and the λmax value was determined. The RP-HPLC method was developed on Sunsil C18 150 mm x 4.6mm x 5μ column using acetonitrile: water [45:55] as mobile phase at flow rate 1.0 ml/min and UV detection at 266 nm. Results: The maximum absorbance was observed at 266 nm. The wavelength 266 nm was selected for further analysis of tolvaptan. The calibration curve was determined using drug concentrations ranging from 20-100 µgm/ml. The system suitability was performed by injecting a standard solution containing 200µg/ml of tolvaptan in six replicates. For two of them, the peak asymmetric were <1.5 and the theoretical plate number was >2000, and the %RSD of tolvaptan was less than 2. Conclusion: From the above results, it was concluded that the developed UV and RP-HPLC methods are precise and accurate and can be applied for the quantitative estimation of tolvaptan from bulk and tablet dosage forms. The method can be used for routine testing of tolvaptan by the pharmaceutical industry. Validation of the developed method was done as per International Conference on Harmonization (ICH) Q2R1 guidelines.

Florian Johann ◽  
Steffen Wöll ◽  
Matthias Winzer ◽  
Jared Snell ◽  
Bernhard Valldorf ◽  

2021 ◽  
Vol 7 (1) ◽  
Shilpi Pathak ◽  
Pradeep Mishra

Abstract Background A stability-indicating RP-HPLC method was developed and validated for the estimation of empagliflozin drug and its tablet dosage form using a DAD detector. The mobile phase consisted of methanol/acetonitrile/0.1%OPA (75:20:5). The peak was observed at 2.54 min using 222.0 nm absorption maxima. Results Calibration curve plot was found within the range of 10–50 µg/mL. The coefficient of determination (R2) was found to be 0.9990. Forced degradation studies were performed for the empagliflozin in various conditions, and the results were calculated as %RSD values and were found to be within the limits. Conclusion The method was validated as per ICH guidelines with respect to all validation parameters.

Parul Grover ◽  
Monika Bhardwaj ◽  
Lovekesh Mehta

David Hayes


Objective: Statistically designed and Box-Behnken design (BBD) assisted reversed-phase high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated for the identification of an antipsychotic medication Olanzapine and its organic impurities in pure drug along with forced degradation studies. Methods: The present developed method employed BBD optimized chromatographic conditions comprising of an Inertsil ODS 3V analytical column with dimension 250 mm x 4.6 mm and particle size 5µ. The isocratic mobile phase was used as a mixture of monobasic sodium phosphate buffer (0.01 M, pH 6), methanol and acetonitrile in the proportion of 40/30/30, v/v. The mobile phase flow rate and UV λmax was 1 ml/min and 260 nm, respectively. The method was optimized by Box-Behnken design using design expert software, comprising of three factors for Olanzapine for instance flow rate (A), mobile phase composition (B) and pH (C) while resolution between Olanzapine related compound A and Olanzapine related compound B (Y1) and tailing of Olanzapine (Y2) were taken as a response. Results: Application of BBD yielded statistically designed method with excellent quality parameters achieved in terms of linearity with the coefficient of correlation (R2>0.9999), limit of detection (LOD, 0.0023-0.16 µg/ml), the limit of quantification (LOQ, 0.007-0.39 µg/ml), accuracy (99-100%) and precision ((2%, relative standard deviation (%RSD) were evaluated as per latest available procedures. Conclusion: Forced degradation conditions were carried out, demonstrated that the optimized method was stable and no any interfering peaks eluting at the similar retention time of the studied compounds. The method was found to be stable, easy, rugged and robust, could be applied for the similar types of the pure drug.

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