A STUDY ON FORCED DEGRADATION AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR DETERMINATION OF BENZALKONIUM CHLORIDE IN AZELASTINE HYDROCHORIDE PHARMACEUTICAL OPHTHALMIC FORMULATION

  • Pratik Kumar Gupta Department of Chemistry, Mewar University, Chittorgarh, Rajasthan, India.
  • Vibha Chaturvedi Department of Chemistry, Mewar University, Chittorgarh, Rajasthan, India.

Abstract

 

 Objective: This study was designed to conduct forced degradation and validation studies for determination the benzalkonium chloride (BKC) as major homologues form in azelastine hydrochloride pharmaceutical ophthalmic formulation by a novel stability indicating reverse phase high-performance liquid chromatographic method (RP-HPLC).

Methods: Forced degradation study and validation were carried out with a analytical approach of reverse phase chromatographic analysis with C18, cosmosil (250mm x 4.6mm i.d. x 5μm) column using mobile phase consisting acetonitrile – buffer of pH 5.0 with 5N NaOH (45:55 %v/v) at a flow rate of 1.5 ml per minute. Column temperature was maintained at 25°C and detection wavelength was 210nm.By using these chromatographic conditions of method, two major homologues of benzalkonium chloride were separated without any interference of drug components and exciepients.

Results: Forced degradation studies were carried out as per ICH guidelines and established a stability indicating property of a method .The method was found linear in concentration range 40μg/ml to 60μg/ml (50μg/ml±20%), correlation coefficient was found 0.999. The recovery was found to be 99.2%, 100.7% and 101.4% at ±30% of target concentration. The %RSD for method precision and intermediate precision were found 0.28% and 0.30 % respectively. The method was found specific, selective, precise, accurate, linear, robust and stability indicating for quantification benzalkonium chloride in azelastine pharmaceutical ophthalmic formulation.

Conclusion: The method has been found successful for determination of BKC pharmaceutical formulation and validated for all the parameters of validation and found within the acceptance criteria as per ICH guideline Q2R1.

Keywords: Benzalkonium chloride content, HPLC, BKC, Preservative, ophthalmic solution, forced degradation.

Author Biography

Pratik Kumar Gupta, Department of Chemistry, Mewar University, Chittorgarh, Rajasthan, India.
Department Of Chemistry, Mewar University, Chittorgarh-312901, Rajasthan (India)

References

1. Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: The good, the bad and the ugly. Prog Retin Eye Res 2010;29(4):312-34.
2. United States Pharmacopeia. USP 40-NF35. Benzalkonium Chloride; 2017. p. 7531-5.
3. Liu J, Lu GW, Sandoval M, Ciringh Y, Xue G, Jaeger D, et al. Determination of benzalkonium chloride partition in micelle solutions using ultrafiltration method. AAPS PharmSciTech 2009;10(4):1216-23.
4. Nelson L, Goldfrank L. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill Medical; 2011.
5. Marple B, Roland P, Benninger M. Safety review of benzalkonium chloride used as a preservative in intranasal solutions: An overview of conflicting data and opinions. Off J Am Acad Otolaryngol Head Neck Surg 2004;130:131-41.
6. Azelastine Hydrochloride Ophthalmic Solution. 0.05%, OPTIVARâ„¢; 2000. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/ label/2000/21127lbl.pdf.
7. Agarwal A, Tiwari S, Nagariya K. Method development and its validation for quantitative simultaneous determination of latanoprost, timolol and benzalkonium chloride in ophthalmic solution by RPHPLC. J Drug Deliv Ther 2013;3(2):26-30.
8. Al-Fakhory AA, Al-Kalak I, Al-Khatib MJ. Chromatographic determination of total benzalkonium chloride [BAC] in some of ophthalmic preparations by HPLC. Damascus Univ J Basic Appl Sci 2014;30:155-71.
9. Chiapetta SC, de Oliveira EC, Olivier BC, Mercante LA, Henriques DM, Pereira Netto AD. Intralaboratory validation, comparison and application of HPLC-UV-DAD methods for simultaneous determination of benzalkonium chloride, chlorexidine digluconate and triclosan. J Braz Chem Soc 2011;22(10):1913-20.
10. Murnane D, Martin G, Marriot C. Validation of reverse phase HPLC method for concurrent assay of weak base and pharmacologically active steroid. J Pharm Biomed Anal 2006;40:1149-54.
11. Gaber M, Shawish HM, Khedr AM, Abed-Almonem KI. Determination of benzalkonium chloride preservative in pharmaceutical formulation of eye and ear drops using new potentiometric sensors. Mater Sci Eng C 2012;32(8):2299-305.
12. Jovovic M, Kostic N, Jancic-Stojanovic B, Malenovic A. Investigation of tropicamide and benzalkonium chloride stability using liquid chromatography. J Liq Chromatogr Relat Technol 2012;32:231-9.
13. Kapakayala SV, Mubeen G, Kimbahune R. Reverse phase-high performance liquid chromatographic method for quantitation of epinastine hydrochloride in eye drops. Indo Am J Pharm Res 2013;3:7541-8.
14. Kostic DA, Mitic SS, Naskovic DC, Zarubica AR, Mitic MN. Determination of benzalkonium chloride in nasal drops by highperformance liquid chromatography. J Chem 2012;9(3):1599-604.
15. Mehta J, Patidar K, Vyas N. Development and validation of a precise method for determination of benzalkonium chloride (BKC) preservative, in pharmaceutical formulation of latanoprost eye drops. J Chem 2010;7:11-20.
16. Rao PV, Venkatesh P, Kumar MR. Validated stability indicating UPLC method for the estimation of benzalkonium chloride in ketorolac tromethamine ophthalmic solution. Int J Chrom Sci 2013;3:5-9.
17. Santos M, Li M, Rustum AM. A single RP-LC method for the determination of benzalkonium chloride and its potential impurities in benzalkonium chloride raw material. Chromatographia 2010;71(5-6):499-503.
18. Shaikh KA, Patil AT. Stability-indicating HPLC method for the determination of mometasone furoate, oxymetazoline, phenyl ethanol and benzalkonium chloride in nasal spray solution. J Trace Anal Food Drugs 2013;1:14-21.
19. Shen Y, Xu SJ, Wang SC, Tu JS. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography. J Zhejiang Univ Sci B 2009;10(12):877-82.
20. Trivedi HK, Patel C. Development and validation of a precise and stability indicating LC method for the determination of benzalkonium chloride in pharmaceutical formulation using an experimental design. J Chem 2010;7:1514-22.
21. Trivedi RK, Challa S, Patel MC, Trivedi DR, Chatrabhuji PM. A rapid, stability-indicating RP-UPLC method for the simultaneous determination of fluticasone furoate and benzalkonium chloride in a pulmonary drug product. Chem Sci Trans 2013;2:1184-91.
22. Dudkiewicz-Wilczynska J, Tautt J, Roman I. Application of the HPLC method for benzalkonium chloride determination in aerosol preparations. J Pharm Biomed Anal 2004;34(5):909-20.
23. Labranche LP, Dumont SN, Levesque S, Carrier A. Rapid determination of total benzalkonium chloride content in ophthalmic formulation. J Pharm Biomed Anal 2007;43(3):989-93.
24. International Conference of Harmonization. ICH Harmonized Tripartite Guideline Validation of Analytical Procedures: Text and Methodology Q2(R1). Geneva: ICH; 2005.
25. Daravath B, Reddy G, Kamarapu SK. Development and validation of RP-HPLC for simultaneous estimation of chlormepheniramine maleate and diethylcarbamzine citrate in pharmaceutical dosage forms. Asian J Pharm Clin Res 2014;7:98-102.
26. Deshpande PB, Butle SR. Development and validation of stability indicating HPTLC method for determination of darunavir ethanolate and ritonavir. Int J Pharm Pharm Sci 2015;7:66-71.
27. Patil PM, Bobade AS. Development and validation of stability indicating RP-HPLC for determination of atorvastatin calcium and ezetimibe in bulk and pharmaceutical dosage forms. Int J Pharm Pharm Sci 2016;8:38-42.
29. Cione AP, Tonhi E, Silva P. Stability Indicating Methods. Brazil: Bioagri Laboratórios, Intech; 2011.
30. Al-Aani H, Al-Nukkary Y. Determination of benzalkonium chloride in ophthalmic solution by stability indicating HPLC method: Application to a stability study. J Appl Pharm Sci 2016;6:80-9.
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Gupta, P. K., and V. Chaturvedi. “A STUDY ON FORCED DEGRADATION AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR DETERMINATION OF BENZALKONIUM CHLORIDE IN AZELASTINE HYDROCHORIDE PHARMACEUTICAL OPHTHALMIC FORMULATION”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 11, Nov. 2017, pp. 374-82, doi:10.22159/ajpcr.2017.v10i11.21701.
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