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

Maja Hadzieva Gigovska, Ana Petkovska, Jelena Acevska, Natalija Nakov, Blagica Manchevska, Packa Antovska, Sonja Ugarkovic, Aneta Dimitrovska

Abstract


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.


Keywords


Atorvastatin, related and degradation products, LC/MS, experimental design, forced degradation

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References


S. Singh, M. Bakshi, Guidance on Conduct of Stress Tests to Determine Inherent Stability of Drugs, Pharm. Technolology 4, 1–14 (2000).

S. Klick, P. G. Muijselaar, J. Waterval, T. Eichinger, C. Korn, T. K. Gerding, A. J. Debets, C. Sänger-van de Griend, C. Van den Beld, G. W. Somsen, et al., Toward a Generic Approach for Stress Testing of Drug Substances and Drug Products, Pharm. Technol., No. February, 48–66 (2005).

M. Blessy, R. D. Patel, P. N. Prajapati, Y. K. Agrawal, Development of Forced Degradation and Stability Indicating Studies of Drugs – A Review, J. Pharm. Anal., 4, (3), 159–165 (2014).

DOI: 10.1016/j.jpha.2013.09.003

M. K. Sharma, M. Murugesan, Forced Degradation Study an Essential Approach to Develop Stability Indicating Method. 8 (1), 8–10 (2017).

DOI: 10.4172/2157-7064.1000349

S. Singh, M. Junwal, G. Modhe, H. Tiwari, M. Kurmi, N. Parashar, P. Sidduri, Forced Degradation Studies to Assess the Stability of Drugs and Products, TrAC - Trends Anal. Chem. 49, 71–88 (2013).

DOI: 10.1016/j.trac.2013.05.006

M. Bakshi, S. Singh, Development of Validated Stability Indicating Assay Methods: Critical Review, J. Pharm. Biomed. Anal. 28 (6), 1011–1040 (2002).

DOI: 10.1016/S0731-7085(02)00047-X

S. Shete, C. Dhale, S. Joshi, Force Degradation Study to Stability Indicating Method, World J. Pharm. Pharm. Sci. 3 (8), 863–873 (2014).

T. P. Aneesh, A. Rajasekaran, Forced Degradation Studies – a Tool for Determination of Stability in Pharmaceutical Dosage Forms, Int. J. Biol. Pharm. Res. 3 (5), 699–702 (2012).

ICH, Stability Testing of New Drug Substances and Products Q1A(R2), Int. Conf. Harmon., No. February, 24 (2003).

R. Singh, Z. Rehman, Current Trends in Forced Degradation Study for Pharmaceutical Product Development, J. Pharm. Educ. Res. 3 (1), 54–64 (2012).

Available at: http://www.pcte.edu.in/jper/issues/2012-

-june-volume-3-issue-1/Paper-7.pdf.

J. Swarbrick, N. Carolina, L. L. Augsburger, H. G. Brittain, A. J. Hickey, C. Hill, Pharmaceutical Stress Testing © 2005, Drugs Pharm. Sci.( 2005).

T. Lundstedt, E. Seifert, L. Abramo, B. Thelin, Å. Nyström, J. Pettersen, R. Bergman, Experimental Design and Optimization., Chemom. Intell. Lab. Syst. 42 (1–2), 3–40 (1998).

DOI: 10.1016/S0169-7439(98)00065-3

M. Kurmi, S. Kumar, B. Singh, S. Singh, Imple¬mentation of Design of Experiments for Optimization of Forced Degradation Conditions and Development of a Stability-Indicating Method for Furosemide, J. Pharm. Biomed. Anal. 96, 135–143 (2014).

DOI: 10.1016/j.jpba.2014.03.035

S. Sonawane, P. Gide, Application of Experimental Design for the Optimization of Forced Degradation and Development of a Validated Stability-Indicating LC Method for Luliconazole in Bulk and Cream Formulation, Arab. J. Chem. (2012).

DOI: 10.1016/j.arabjc.2012.03.019

S. Sonawane, P. Gide, Optimization of Forced Degra¬dation Using Experimental Design and Development of a Stability-Indicating Liquid Chromatographic Assay Method for Rebamipide in Bulk and Tablet Dosage Form, Sci. Pharm. 79 (1), 85–96 (2011).

DOI: 10.3797/scipharm.1011-06

S. Sonawane, P. Gide, An Experimental Design Approach for the Forced Degradation Studies and Development of a Stability indicating Lc Method for Eplerenone in Tablets, J. Liq. Chromatogr. Relat. Technol. 34 (17), 2020–2031( 2011).

DOI: 10.1080/10826076.2011.582913

P. Kathleen, Martindale: The Complete Drug Reference, 32nd ed.; Pharmaceutical Press: London, 1999.

Bernard, S.; Mathew, M.; Senthilkumar, K. L.; Girija, K. N. A validated stability indicating reversed phase HPLC method for the determination of atorvastatin calcium. International Journal of Drug Formulation and Research, 1, 9–19 (2013).

S. Dahiya, Stability-indicating RP-HPLC Method for Estimation of Atorvastatin Calcium in Solid Dosage Form, Bull. Pharm. Res. 4 (1), 9–13 (2014).

M. S. Charde, A. Gupta, R. D. Chakole, Simultaneous Determination of Atorvastatin Calcium and Telmisartan in Pharmaceutical Formulations by Reverse Phase-High Performance Liquid Chromatography, Inter. J. Pharm. Chem. 2 (1), 1–6 (2012).

K. K. Kumar, C. K. Rao, A Validated Stability Indicating RP-UPLC Method for Atorvastain Calcium, American Journal of Analytical Chemistry, 3, 392–399 (2012).

M. Kračun, A. Kocijan, A. Bastarda, R. Grahek, J. Plavec, D. Kocjan, Isolation and Structure Deter¬mination of Oxidative Degradation Products of Atorvastatin, J. Pharm. Biomed. Anal. 50 (5), 729–736 (2009). DOI: 10.1016/j.jpba.2009.06.008

M. A. Oliveira, M. I. Yoshida, V. J. Belinelo, R. S Valotto, Degradation Kinetics of Atorvastatin under Stress Conditions and Chemical Analysis by HPLC. Molecules, 18 (2), 1447–1456 (2013).

DOI: 10.3390/molecules18021447

E. Rudwan, A. Mohammed, A. Saeed, A New RP-HPLC Method for Quantitative Analysis of Atorvastatin Calcium in Bulk and Pharmaceutical Dosage Form by Using Design of Experiment Technique Optimization, Int. Res. J. Pure Appl. Chem., 13 (4), 1–10 (2016).

DOI: 10.9734/IRJPAC/2016/31250

L. D. Simionato, L. Ferello, S. G. Stamer, M. F. Repetto, P. D. Zubata, A. I. Segall, A Validated Reversed ­ Phase HPLC Method for the Determination of Atorvastatin Calcium in Tablets Chromatographic Conditions. Austin Chromatogr, 1 (1), 1–5 (2014).

K. Pushpa Latha, D. Ramachandran, Validation of HPLC Method for Determination of Atorvastatin in Tablets and Identify Diketone Impurity by LC-Mass, Int. J. ChemTech Res. 5 (5), 2429–2435 (2013)

Z. Zaheer, M. N. Farooqui, A. P. G. Nikalje, A. A. Mangle, Stability-Indicating High Performance Liquid Chromatographic Determination of Atorvastatin Calcium in Pharmaceutical Dosage Form, African J. Pharm. Pharmacol. 2 (10), 204–210 (2008)

European Pharmacopoeia, 8th ed., European Direc-torate for the Quality of Medicines – Council of Europe, Strasbourg, 2014. Atorvastatinum calcicum trihydricum monograph 04/2011:2191. 1598–1599

R. P. Shah, V. Kumar, S. Singh, Liquid Chromatography/Mass Spectrometric Studies on Atorvastatin and Its Stress Degradation Products, Rapid Commun Mass Spectrom . 22, 613–622 (2008)

DOI https://doi.org/10.1002/rcm.3403

P. Vukkum, J. Moses Babu, R. Muralikrishna, Stress Degradation Behavior of Atorvastatin Calcium and Development of a Suitable Stability-Indicating LC Method for the Determination of Atorvastatin, Its Related Impurities, and Its Degradation Products, Sci. Pharm. 81 (1), 93–114 (2013). DOI: 10.3797/scipharm.1208-06




DOI: http://dx.doi.org/10.20450/mjcce.2018.1471

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