Stress Degradation Behavior of a Polypill and Development of Stability Indicating UHPLC Method for the Simultaneous Estimation of Aspirin, Atorvastatin, Ramipril and Metoprolol Succinate

Satheesh Kumar Shetty, K.V Surendranath, P Radhakrishnanand, Roshan M Borkar, Prashant S Devrukhakar, Johnson Jogul, Upendra Mani Tripathi

.

DOI: 10.4236/ajac.2011.24049                

Abstract

A novel, sensitive and precise UHPLC method has been developed and validated for the simultaneous determination of the all the active components of a Polypill viz Zycad, i.e., Aspirin (ASP) Atorvastatin (ATV), Ramipril (RMP) and Metoprolol (MTP) in Zycad tablet dosage form in the presence of degradation products. Forced degradation of individual as well as combination of all the drug substances components of Polypill was conducted in accordance with ICH guidelines. Acidic, basic, neutral, and oxidative hydrolysis, thermal stress, and photolytic degradation were used to assess the stability-indicating power of the method. Use of 100 × 2.1 mm, 1.7 µm stationary phases with simple mobile phase combination buffer consisting of 0.1% Perchloric acid (adjusted to pH 2.5) and Acetonitrile, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 215 nm with a flow rate of 0.6 mL?min–1. The method was optimized using samples generated by forced degradation studies. The method was validated for linearity, accuracy (recovery), precision, Specificity and robustness. The method was linear in the range of 37.5 to 150.0 µg?mL–1 for ASP, 5.0 to 20.0 µg?mL–1 for ATV and 2.5 to 10.0 µg?mL–1 for RMP and 25.0 to 100.0 µg?mL–1 for MTP.

Keywords

Liquid Chromatography; UHPLC, Polypill, Aspirin, Atorvastatin, Ramipril And Metoprolol Succinate; Forced Degradation; Validation; Stability Indicating

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	G. Sanz and V. Fuster, “Fixed-Dose Combination Therapy and Secondary Cardiovascular Prevention: Rationale, Selection of Drugs and Target Population,” Nature Clin-ical Practice Cardiovascular Medicine, Vol. 6, No. 2, 2009), pp. 101-110. doi:10.1038/ncpcardio1419
[2]	“Global Burden of Disease 2004 Update,” World Health Organization, 2008.
[3]	C. D. Mathers and D. Loncar, “Projections of Global Mortality and Burden of Disease from 2002 to 2030,” PLoS Medicine, Vol. 3, No. 11, 2006, p. e442. doi:10.1371/journal.pmed.0030442
[4]	M. R. Law and N. J. Wald, “Risk Factor Thresholds: Their Existence under Scrutiny,” British Medical Journal, Vol. 324, No. 7353, 2002, pp. 570-576. doi:10.1136/bmj.324.7353.1570
[5]	V. Kumar, R. P. Shah and S. Singh, “LC and LC–MS Methods for the Investigation of Polypills for the Treat-ment of Cardiovascular Diseases: Part.1 Separation of Active Compo,” Journal of Pharmaceutical and Biomed-ical Analysis, Vol. 47, 2008, pp. 508-515. doi:10.1016/j.jpba.2008.01.041
[6]	S. P. Clissold, “Aspirin and Related Derivatives of Sali-cylic Acid,” Drugs, Vol. 32, 1986, pp. 8-26. doi:10.2165/00003495-198600324-00003
[7]	D. G. Julian, D. A. Chamberlain and S. J. Pocock, “A Comparison of Aspirin and Anticoagulation Following Thrombolysis for Myocardial Infarction (the AFTER Study): A Multicentre Unblinded Randomized Clinical Trial,” BMJ (British Medical Journal), Vol. 313, No. 7070, 1996, pp. 1429-1431.
[8]	J. W. Nawrocki, S. R. Weiss, M. H. Davidson, D. L. Sprecher, S. L. Schwartz, P. J. Lupien, P. H. Jones, H. E. Haber, et al., “Reduction of LDL Cholesterol by 25% to 60% in Patients with Primary Hypercholesterolemia by Atorvastatin, a New HMG-CoA Reductase Inhibitor,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 15, No. 5, May 1995, pp. 678-682. doi:10.1161/01.ATV.15.5.678
[9]	L. Pilot, M. Abrahamowicz, M. Eisenberg, K. Humphries, H. Behlouli and J. V. Tu, “Effect of Different Angioten-sin-Converting-Enzyme Inhibitors on Mortality among Elderly Patients with Congestive Heart Failure,” Canadian Medical Association Journal, Vol. 178, No. 10, 2008, pp. 1303-1311. doi:10.1503/cmaj.060068
[10]	Q. Zhang, H. Jin, L. Wang, J. Chen, C. Tang and J. Du, “Randomized Comparison of Metoprolol Versus Con-ventional Treatment in Preventing Recurrence of Vaso-vagal Syncope in Children and Adolescents,” International Medical Journal of Experimental and Clinical Research, Vol. 14, No. 4, pp. 199-203.
[11]	E. R. Montgomery, S. Taylor, J. Segretario, et al., “De-velopment and Validation of a Reversed-Phase Liquid Chromatographic Method for Analysis of Aspirin and Warfarin in a Combination Tablet Formulation,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 15, No. 1, 1996, pp. 73-82.
[12]	S. Erturk, A. E. Sevinc, L. Ersoy and S. Ficicioglu, “HPLC Method for the Determination of Atorvastatin and Its Impurities in Bulk Drug and Tablets,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 33, No. 5, 2003, pp. 1017-1023. doi:10.1016/S0731-7085(03)00408-4
[13]	A. Puratchikody, R. Valarmathy and P. Shiju, “RP-HPLC Determination of Atorvastatin Calcium in Solid Dosage Forms,” Journal of Pharmacological Reviews, 2003, pp. 79-80.
[14]	H. J. Panchal, B. N. Suhagia, N. J. Patel, I. S. Rathod, B. H. Patel, “Development and Validation of a HPTLC Me-thod for the Simultaneous Estimation of Atorvastatin Calcium and Ezetimibe,” Chromatographia, Vol. 69, No. 1-2, 2009, pp. 91-95. doi:10.1365/s10337-008-0831-z
[15]	F. Belal, I. A. Al-Zaagi, E. A. Gadkariem and M. A. Ab-ounassif, “A Stability-Indicating LC Method for the Si-multaneous Determination of Ramipril and Hydrochloro-thiazide in Dosage Forms,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 24, No. 3, 2001, pp. 335-342. doi:10.1016/S0731-7085(00)00474-X
[16]	M. B. Shankar, F. A. Metha, K. K. Bhatt, R. S. Metha and M. Geetha, “Simultaneous spectrophotometric determi-nation of losartan potassium and hydrochlorothiazide in tablets,” Indian Journal of Pharmaceutical Sciences, Vol. 65, No. 2, 2003, pp. 167-170.
[17]	“ICH Stability Testing of New Drug Substances and Products Q1A (R2),” International Conference on Har-monization, IFPMA, Geneva, 2003.
[18]	“ICH guidelines on Validation of Analytical Procedures, Text and Methodology Q2 (R1),” FDA, Published in the Federal Register 60, 1995.
[19]	“United States Pharmacopoeia,” 32nd Edition, United States Pharmacopeial Convention, Rockville, USP 32, 2009.
[20]	M. Bakshi and S. Singh, “Development of Validated Stability-Indicating Assay Methods-Critical Review,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 28, 2002, pp. 1011-1040.