DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF AZILSARTAN MEDOXIMIL AND CHLORTHALIDONE IN BULK FORM AND FORMULATION USING QUALITY BY DESIGN
Objective: Development of an accurate, precise, robust, sensitive, economical and rapid isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method complying quality by design (QbD) trends for simultaneous estimation of azilsartan medoximil and chlorthalidone in bulk and formulation form and validation of the method as per ICH guidelines.
Methods: The simultaneous estimation of the drugs-azilsartan and chlorthalidone was performed using C8 column having dimensions 150Ã—4.6 mmÃ—5 Âµm, injection volume 10 Âµl, flow rate 0.8 ml/min., runtime 10 min., column temperature 20 oC, sampler temperature 5 Â°C and ultraviolet detection using a photodiode array detector at 220 nm as constant. The optimized method was validated as per ICH guidelines.
Results: The retention times for chlorthalidone and azilsartan medoxomil were 2.4 min. and 5.1 min. respectively with resolution 17. The method was validated as per the ICH guidelines. The linearity of chlortalidone and azilsartan medoxomil was in the range of 6.3 to 15 Âµg/ml and 20 to 48 Âµg/ml respectively. The potency of the formulation was found to be 108.12 % and 98.20 % respectively, which are within acceptable limits as per IP.
Conclusion: Method validation results have proven the method to be selective, precise, accurate, and robust, as well as stability indicating. The C8 column used for analysis gave encouraging results with better resolution and less retention time. This method can be successfully applied for the routine analysis involving the determination of content uniformity and dissolution profiling as well as stability study by the industry.
Keywords: RP-HPLC, QbD, ICH, Azilsartan medoximil, Chlorthalidone.
2. Perry CM. Azilsartan medoxomil: a review of its use in hypertension. Clin Drug Invest 2012;32:621-39.
3. http://pharmacy.hsc.wvu.edu/media/1137/edarbyclor-azilsartan-chlorthalidone.pdf. [Last accessed on 15 Apr 2013].
4. Jones JD, Jackson SH, Agboton C, Martin TS. Azilsartan medoximil (edarbi). The Eighth Angiotensin II Receptor Blocker. P T 2011;36:634-6, 638-40.
5. Zaiken K, Cheng JW. Azilsartan medoxomil: a new angiotensin receptor blocker. Clin Ther 2011;33:1577â€“89.
6. Sica DA. Rationale for the use of fixed-dose combinations in the treatment of hypertension: the cycle repeats. Drugs 2002;62:2761â€“88.
7. Woodman R, Brown C, Lockette W. Chlorthalidone decreases platelet aggregation and vascular permeability and promotes angiogenesis. Hypertension 2010;56:463-70.
8. BÃ¶nner G, Bakris GL, Sica D. Comparison of antihypertensive efficacy of the new angiotensin receptor blocker azilsartan medoxomil with ramipril. J Hypertension 2010;28:283.
9. Weber MA, White WB, Sica D. Antihypertensive efficacy of the novel angiotensin receptor blocker azilsartan medoxomil in combination with amlodipine. J Hypertension 2010;28:279â€“80.
10. Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A, et al. Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med 2012;125:1229.e1-1229.e10.
11. White WB, Weber MA, Sica D. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension 2011;57:413â€“20.
12. Sica D, Bakris GL, White WB. New angiotensin II receptor blocker azilsartan medoxomil coadministered with chlorthalidone provides potent blood pressure reduction in stage 2 hypertension. J Clin Hypertens 2010;12:A114.
13. Cushman WC, Bakris GL, White WB. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorthiazide in stage2 systolic hypertension. Hypertension 2012;60:310â€“8.
14. Ernst ME, Carter BL, Goerdt CJ. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 2006;47:352-8.
15. http://www.takeda.us/newsroom/press_release_detail.aspx?id=231. [Last accessed on 07 Feb 2013].
16. Pierini D, Anderson KV. Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. Ann Pharmacother 2013;47:694-703.
17. Gorla R, Nagaraju CH, Sreenivasulu B, Sreenivas N, Korupolu RB. New simple UV Spectrophotometric method for determination of Azilsartan medoxomil in bulk and pharmaceutical dosage forms. Int J Res Pharm Biomed Sci 2013;4:1133-7.
18. Kasimala MB, Kasimala BB. Reverse phase-HPLC method development and validation for the simultaneous estimation of azilsartan medoxomil and chlortalidone in pharmaceutical dosage form. Jamonline 2012;2:117â€“26.
19. Sravani P, Rubesh S, Duganath N, Devanna N. Method development and validation for the simultaneous estimation of Azilsartan and Chlorthalidone by RP-HPLC in pharmaceutical dosage form. Indian J Pharm Sci 2014;4:725-9.
20. http://www.glsciences.com. [Last accessed on 16 Mar 2013].
21. Patil AS, Pethe AM. Quality by design (QbD): a new concept for development of quality pharmaceuticals. IJQPA 2013;4:13-9.
22. Vogt FG, Kord AS. Development of quality-by-design analytical methods. J Pharm Sci 2010;100:797-812.
23. Drenne JK. Quality by designâ€“what does it really mean. J Pharm Innovation 2007;2:65-6.
24. International Conference on Harmonisation (ICH), Validation of analytical procedures: text and methodology Q2 (R1); 2005.
25. International Conference on Harmonisation (ICH),, Specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances, Q6A; 1999.