Validation of Stability Indicating Method and Degradation Kinetic Study of Apremilast
A novel stability indicating RP- HPLC method was developed for the estimation of Apremilast in bulk and marketed formulation. Separation was achieved by using Shimadzu HPLC Analytical Technologies Limited C18 (250 mm x 4.6 mm, 5µm) as stationary phase. The optimized mobile phase consist of potassium dihydrogen ortho phosphate (pH-3.2): acetonitrile in ratio of 40:60 %v/v with flow rate of 1mL/min by using methanol as diluent. Retention time of Apremilast was found to be 5.4 min which was estimated at wavelength 360nm. Linearity of Apremilast was observed in the concentration range of 50-400µg/mL with r² value of 0.9999. Assay of Apremilast tablet was found to be 99.14-100.75%. Stability indicating nature of RP- HPLC method was estimated by conducting degradation kinetic study. The forced degradation of Apremilast bulk indicate that degradation in acidic, alkali, oxidative and photolysis condition were found to be 21%, 6.5%, 25.7% and 3.9% respectively. The kinetic study of apremilast in alkali degradation followed first order kinetic study. The result indicate that the developed RP-HPLC method is suitable for estimation of Apremilast in presence of degradant product. The above method was validated as per ICH guideline.
Keywords: Apremilast, RP-HPLC, Validation, Forced Degradation Study, Alkali Degradation Kinetic study
2. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochemical pharmacology. 2012 Jun 15; 83(12):1583-90.
3. Xiong K, Ma X, Cao N, Liu L, Sun L, Zou Q, Wei P. Identification, characterization and HPLC quantification of impurities in apremilast. Analytical Methods. 2016;8(8):1889-97.
4. Landge SB, Dahale SB, Jadhav SA, Solanki PV, Bembalkar SR, Mathad VT. Development and validation of stability indicating rapid RP-LC method for determination of process and degradation related impurities of Apremilast, an anti-inflammatory drug. Am J Anal Chem. 2017 Jun 12; 8:380.
6. Chaudhari SR, Shirkhedkar AA. Design of Experiment Avenue for development and validation of RP-HPLC-PDA method for determination of apremilast in bulk and in in-house tablet formulation. Journal of Analytical Science and Technology. 2019 Dec; 10(1):10. 8.https://www.gmp-compliance.org/guidelines/gmp-guideline/ich-q2r1-validation-of- analytical-procedures-text-and-methodology
7. Lonkar N, Sawant S, Dole M. Development and validation of stability indicating RP-HPLC method for the estimation of apremilast by forced degradation studies. W. J Pharm Pharm Sci. 2017a. 2017; 6:1493-502
8. Badhe P, Aher S, Saudagar RB. Analytical Method of Apremilast: A Review. Journal of Drug Delivery and Therapeutics. 2019 Jun 29; 9(3-s):1116-9.
9. Bhole RP, Naksakhare SR, Bonde CG. A Stability Indicating HPTLC Method for Apremilast and Identification of degradation products using MS/MS. Journal of Pharmaceutical Sciences and Research. 2019 May 1; 11(5):1861-9.
10. Ravisankar P, Sulthana MS, Babu PS. Development and validation of stability-indicating UV spectrophotometric method for determination of Apremilast in bulk and pharmaceutical dosage form. Ind J Res Pharm Biotechnol. 2017; 5:47. 14.https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-2-r1-validation- analytical-procedures-text-methodology-step-5_en.pdf
11. Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, Hu C, Day RM. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. The Lancet. 2012 Aug 25; 380(9843):738-46.
12. Pandya CP, Rajput SJ. Stress Degradation Studies of Anagliptin, Development of Validated Stability Indicating Method, Degradation Kinetics Study, Identification and Isolation of Degradation Products. Chromatographia. 2018 Nov 1; 81(11):1533-50.
13. Pandya CP, Rajput SJ. Stress Degradation Studies of Riociguat, Development of Validated Stability Indicating Method, Identification, Isolation and Characterization of Degradation Products by LC-HR-MS/MS and NMR Studies. Indian Journal Of Pharmaceutical Education And Research. 2019 Oct 1; 53(4):S630-41.
14. Bockhorn H, Hornung A, Hornung U, Schawaller D. Kinetic study on the thermal degradation of polypropylene and polyethylene. Journal of Analytical and Applied Pyrolysis. 1999 Jan 1; 48(2):93-109.
15. SHRIMALI C, BAGHEL M, RAJPUT S. Development and validation of stability indicating rp-hplc method of nepafenac and its degradation products: application to degradation kinetic. Int J Pharm Pharm Sci. 2014; 6(9):387-93.
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