scholarly journals FORCED DEGRADATION STUDY OF STATINS: A REVIEW

2018 ◽  
Vol 10 (6) ◽  
pp. 38
Author(s):  
Rini Yulianita ◽  
Iyan Sopyan ◽  
Muchtaridi Muchtaridi
Keyword(s):  
Degradation Products ◽  
Storage Conditions ◽  
Lipid Lowering ◽  
Forced Degradation ◽  
Degradation Study ◽  
Drug Degradation ◽  
Drug Products ◽  
Drug Substances ◽  
Accelerated Stability ◽  
Forced Degradation Studies

Forced degradation study is the degradation of new drug substances and drug products in more severe conditions than accelerated conditions. Forced degradation study were conducted to demonstrate the specificity of stability-indicating methods, providing insight into degradation pathways and drug degradation products, assisting in the elucidation of degradation product structures, identifying degradation products that could be spontaneously generated during storage and use of drugs and to facilitate improvement in manufacturing process and formulation corresponding with accelerated stability studies. Statins, a class of lipid-lowering medications, are the most widely prescribed drugs and an example of an unstable drug. Statins are susceptible to hydrolysis in the presence of high temperatures and humidity. Therefore, the review discusses various studies of forced degradation studies in six statins drug (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) to describe the drug's intrinsic stability thus it can assist the selection of formulations and packaging as well as proper storage conditions.

scholarly journals Determination of Rosuvastatin in the Presence of Its Degradation Products by a Stability-Indicating LC Method

2005 ◽  
Vol 88 (4) ◽  
pp. 1142-1147 ◽  
Author(s):  
Tushar N Mehta ◽  
Atul K Patel ◽  
Gopal M Kulkarni ◽  
Gunta Suubbaiah
Keyword(s):  
Degradation Products ◽  
Stability Study ◽  
Tablet Formulation ◽  
Assay Method ◽  
Forced Degradation ◽  
Degradation Study ◽  
Stability Indicating ◽  
Degraded Samples ◽  
Accelerated Stability

Abstract A forced degradation study was successfully applied for the development of a stability-indicating assay method for determination of rosuvastatin Ca in the presence of its degradation products. The method was developed and optimized by analyzing the forcefully degraded samples. Degradation of the drug was done at various pH values. Moreover, the drug was degraded under oxidative, photolytic, and thermal stress conditions. Mass balance between assay values of degraded samples and generated impurities was found to be satisfactory. The proposed method was able to resolve all of the possible degradation products formed during the stress study. The developed method was successfully applied for an accelerated stability study of the tablet formulation. The major impurities generated during the accelerated stability study of the tablet formulation were matches with those of the forced degradation study. The developed method was validated for determination of rosuvastatin Ca, and the method was found to be equally applicable to study the impurities formed during routine and forced degradation of rosuvastatin Ca.

scholarly journals Identification of degradation impurity of TGR5 receptor agonist-ZY12201 by LC–MS technique during force degradation study

2021 ◽  
Vol 3 (6) ◽  
Author(s):  
Chandrakant Sojitra ◽  
Chintan Dholakia ◽  
Padmaja Sudhakar ◽  
Kumar K. Singh ◽  
Sameer Agarwal
Keyword(s):  
Degradation Products ◽  
Oxidative Degradation ◽  
Active Pharmaceutical Ingredient ◽  
Storage Conditions ◽  
Receptor Activation ◽  
Degradation Pathway ◽  
Forced Degradation ◽  
Degradation Study ◽  
Glucagon Like Peptide 1 ◽  
Orally Bioavailable

AbstractForced degradation study is a systemic characterization of degradation products of active pharmaceutical ingredient (API) at conditions which posses more harsh environment that accelerates degradation of API. Forced degradation and stability studies would be useful in selection of proper, packaging material and storage conditions of the API. These are also useful to demonstrate degradation pathways and degradation products of the API and further characterisation of the degradation products using mass spectrometry. TGR5 is a G protein-coupled receptor, activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The potent and orally bioavailable TGR5 agonist, ZY12201, shows activation of TGR5 which increase secretion of GLP-1 and help in lowering blood glucose level in animal models. Hence it is necessary to establish and study degradation pathway and stability of API for better handling and regulatory approval. Force degradation studies of ZY12201 have shown presence of one oxidative impurity during oxidative degradation in HPLC analysis. The oxidized product is further characterized by LC–MS to elucidate structure of impurity and characterize its degradation pathway.

scholarly journals Current Trend in Performance of Forced Degradation Studies for Drug Substance and Drug Product’s

2020 ◽  
Vol 10 (2-s) ◽  
pp. 149-155
Author(s):  
Rajveer Bhaskar ◽  
Monika Ola ◽  
Vinit Agnihotri ◽  
Arjun Chavan ◽  
Harpalsing Girase
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Drug Product ◽  
Current Trend ◽  
Forced Degradation ◽  
Regulatory Requirement ◽  
New Drug ◽  
Drug Substances ◽  
Forced Degradation Studies ◽  
Degradation Studies

The stability of a new drug substances and new drug products is a vital parameter which may affect purity, safety & potency. Changes in drug stability can threat patient safety by formation of toxic degradation products or deliver to lower dose than expected. Therefore it is to know the purity profile & behaviour of a drug substances under the various environmental condition.  Forced Degradation studies show the chemical behavior of the molecule which in turn helps in the  development of  new formulation & package . Degradation study is required to the design of a regulatory compliant stability program for the both drug substances & products, and formalized as a regulatory requirement in ICH Guideline Q1A in 1993. Forced degradation studies (chemical and physical stress testing) of new chemical entities and drug product which is required to develop and demonstrate the specificity i.e stability indicating method. Forced degradation studies used to determination of the degradation pathways and degradation product of drug substances i.e during storage, development, manufacturing and packaging Thus , this review discusses the current trends in performance of forced degradation studies by provide the information about strategy for conducting the studies of forced degradation Keywords: - Regulatory Guidelines (ICH, FDA, EMA), Degradation condition, Forced degradation, Degradation product.

scholarly journals Development and Stability of Forced Degradation Studies Indicating Different Brands of Metformin Drugs

2021 ◽  
pp. 54-60
Author(s):  
A. J. Giri ◽  
Anjali D Kingre ◽  
J. K. Dhumal ◽  
P. R. Doifode ◽  
Pratiksha Jaybhaye ◽  
...  
Keyword(s):  
Drug Product ◽  
Forced Degradation ◽  
Chemical Behavior ◽  
Regulatory Requirement ◽  
Degradation Study ◽  
Essential Step ◽  
Drug Substances ◽  
Forced Degradation Studies ◽  
Degradation Studies ◽  
Ich Guideline

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.

scholarly journals Optimization of a forced degradation study of atorvastatin employing an experimental design approach

2018 ◽  
Vol 37 (2) ◽  
Author(s):  
Maja Hadzieva Gigovska ◽  
Ana Petkovska ◽  
Jelena Acevska ◽  
Natalija Nakov ◽  
Blagica Manchevska ◽  
...  
Keyword(s):  
Experimental Design ◽  
Ion Trap ◽  
Degradation Products ◽  
Forced Degradation ◽  
Experimental Conditions ◽  
Liquid Chromatograph ◽  
Degradation Study ◽  
Mobile Phases ◽  
Forced Degradation Studies ◽  
Full Factorial

This study involved the optimization of experimental conditions for the forced degradation of atorvastatin employing the experimental design (DoE) approach, as a scientific multifactorial strategy. Using 2n full factorial design, stress conditions of oxidative, hydrolytic and thermal degradation were optimized to obtain a targeted level of atorvastatin degradation. Atorvastatin and all related and degradation products were separated on Poroshell 120 EC C18 50 ´ 3.0 mm 2.7 μm, using 10 mM ammonium formate and acetonitrile as mobile phases in the gradient mode. The impurity structures were confirmed by the direct hyphenation of a liquid chromatograph to an ion trap mass spectrometer with a heated electrospray ionization interface.This study highlights the multifold benefits of implementing the DoE concept, which provides a better understanding of the significant factors responsible for degradation and ensures a successful way to achieve degradation, thereby replacing the trial and error approach used in conventional forced degradation studies.

SIGNIFICANCE OF FORCED DEGRADATION STUDIES FOR DRUG SUBSTANCE AND DRUG PRODUCTS WITH REFERENCE TO ANTIHYPERTENSIVE AGENTS

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (01) ◽  
pp. 5-17
Author(s):  
J. G Modi ◽  
◽  
J. K Patel ◽  
N. A Gohel ◽  
K. G Modi ◽  
...  
Keyword(s):  
Degradation Products ◽  
Drug Product ◽  
Antihypertensive Agents ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Product ◽  
Stress Conditions ◽  
Drug Substance ◽  
Forced Degradation ◽  
Degradation Study ◽  
Drug Products

Stability testing is used to provide evidence of how the quality of an Active Pharmaceutical Ingredient (API) or drug product varies with time under the infuence of a variety of environmental factors such as temperature, humidity and light. If drug product is not stable under various environmental conditions, it may affect the patient safety by formation of a toxic degradation product(s) or deliver a lower dose than expected. Stress testing of the API can help to identify the likely degradation products, which, in turn, can help to establish the degradation pathways and the intrinsic stability of the molecule. Forced degradation study is a process in which the natural degradation rate of a pharmaceutical product is increased by applying an additional stres by which stability of a drug substance or a drug product with effects on purity, potency and safety can be predicted. The present review summarizes the forced degradation study of antihypertensive agents, where degradation products for different stress conditions have been reported. As per review, maximum degradation products have been reported by alkaline, oxidative and photolytic stress conditions.

Synthesis and Characterization of Potential and Degraded Impurities of Regadenoson

2020 ◽  
Vol 16 (8) ◽  
pp. 1130-1139
Author(s):  
Singaram Sathiyanarayanan ◽  
Chidambaram Subramanian Venkatesan ◽  
Senthamaraikannan Kabilan
Keyword(s):  
Mass Spectra ◽  
Degradation Products ◽  
Hplc Method ◽  
Forced Degradation ◽  
Spectroscopic Techniques ◽  
A2a Adenosine Receptor ◽  
Degradation Study ◽  
Related Substances ◽  
Adenosine Receptor Agonist

Background: Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator and commonly used as a pharmacologic cardiac stressing agents. Methods: HPLC method was used for the analysis of related substances. The degraded impurities during the process were isolated and characterized by IR, Mass and NMR spectral analysis. Results: Forced degradation study of regadenoson under conditions of hydrolysis (neutral, acidic and alkaline) and oxidations suggested in the ICH Q1A(R2) was accomplished. The drug showed significant degradation under all the above conditions. On the whole, five novel degradation products were found under diverse conditions along with process related impurities which were not reported earlier. Conclusion: All the degradation products were well characterized by using advanced spectroscopic techniques like IR, 1H NMR, 13C NMR and Mass spectra. The identification of these impurities will be productive for the quality control during the production and stability behavior of the regadenoson drug substance.

Validation of Analytical Methods for Tacrolimus Determination in Poly(ε-caprolactone) Nanocapsules and Identification of Drug Degradation Products

2021 ◽  
Vol 21 (12) ◽  
pp. 5920-5928
Author(s):  
Guilherme A. Camargo ◽  
Amanda M. Lyra ◽  
Fernanda M. Barboza ◽  
Barbara C. Fiorin ◽  
Flávio L. Beltrame ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Degradation Products ◽  
Multiple Reaction Monitoring ◽  
Forced Degradation ◽  
Alkaline Stress ◽  
Drug Degradation ◽  
Relative Standard ◽  
Polymeric Nanocapsules ◽  
Alkaline Conditions

The aim of this paper was to use chromatographic tools for validating an analytical method for the tacrolimus (TAC) determination in polymeric nanocapsules and for identifying the drug degradation products after alkaline stress. A rapid Ultra-High-Performance Liquid Chromatography coupled with photo-diode array (UHPLC-PDA) method was successfully performed using the following chromatographic conditions: the Shimadzu Shim-pack XR-ODS III C18 column (100 mm×2.00 mm, 2.2 μm), the mobile phase consisting of methanol and acidified ultrapure water (89:11 v/v), the flow rate of 0.55 mL·min−1, and the ultraviolet (UV) detection at 235 nm. This method was validated as per International Council for Harmonisation (ICH) guidelines. In addition, a TAC forced degradation assay was carried out after alkaline stress and its degradation products were investigated using Liquid Chromatography coupled tandem mass spectroscopy (LC-MS/MS). The calibration curve was linear in the range of 100.0–300.0 μg·mL−1 (r >0.9999). Accuracy was confirmed by the TAC recovery of 96.55 to 98.19%. Precision (intraday and interday) were demonstrated by relative standard deviation lower than 0.89% and 3.25%, respectively. Selectivity and robustness were also proved. The method developed it was successfully applied to quantify TAC from polymeric nanocapsules, showing a high loading efficiency rate (>96.47%). The main drug degradation product observed in a multiple reaction monitoring (MRM) experiment was m/z 844, confirming the susceptibility of TAC under alkaline conditions; this finding was first time described.

scholarly journals RP-HPLC assay method development for Paracetamol and Lornoxicam in combination and characterization of oxidative degradation products of Lornoxicam

2013 ◽  
Vol 19 (4) ◽  
pp. 471-484
Author(s):  
Pritam Jain ◽  
Miketa Patel ◽  
Amar Chaudhari ◽  
Sanjay Surana
Keyword(s):  
Method Development ◽  
Degradation Products ◽  
Oxidative Degradation ◽  
Assay Method ◽  
Forced Degradation ◽  
Control Analysis ◽  
Reverse Phase ◽  
Solution Form ◽  
Forced Degradation Studies ◽  
Degradation Studies

A simple, specific, accurate and precise reverse phase high pressure liquid chromatographic method has been developed for the simultaneous determination of Paracetamol and Lornoxicam from tablets and to characterize degradation products of Lornoxicam by reverse phase C18 column (Inertsil ODS 3V C-18, 250 x 4.6 mm, 5 ?). The sample was analyzed using Buffer (0.02504 Molar): Methanol in the ratio of 45:55, as a mobile phase at a flow rate of 1.5 mL/min and detection at 290 nm. The retention time for Paracetamol and Lornoxicam was found to be 2.45 and 9.40 min respectively. The method can be used for estimation of combination of these drugs in tablets. The method was validated as per ICH guidelines. The linearity of developed method was achieved in the range of 249.09 - 747.29 ?g/mL (r2=0.9999) for Paracetamol and 4.0125 - 12.0375 ?g/mL (r2=0.9999) for Lornoxicam. Recoveries from tablets were between 98 and 102%. The method was validated with respect to linearity, accuracy, precision, robustness and forced degradation studies which further proved the stability-indicating power. During the forced degradation studies lornoxicam was observed to be labile to alkaline hydrolytic stress and oxidative stress (in the solution form). However, it was stable to the acid hydrolytic, photolytic and thermal stress (in both solid and solution form). The degraded products formed were investigated by electrospray ionization (ESI) time-of-flight mass spectrometry, NMR and IR spectroscopy. A possible degradation pathway was outlined based on the results. The method was found to be sensitive with a detection limit of 0.193 ?g/ml, 2.768 ?g/ml and a quantitation limit of 0.638 ?g/ml, 9.137 ?g/ml for lornoxicam and paracetamol, respectively. Due to these attributes, the proposed method could be used for routine quality control analysis of these drugs in combined dosage forms.

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