Development and Validation of Simultaneous Quantitative Dissolution Analysis for the Two Active Pharmaceutical Ingredients in Dapagliflozin
Propanediol Monohydrate-sitagliptin Phosphate Monohydrate Multi-layered Tablets

Ji-Hye      Shin; Joo-Eun      Kim

doi:10.2174/0115734129270782231123103912

Abstract

Background: Recently, a combination prescription with the main ingredients sitagliptin and dapagliflozin as dipeptidyl peptidase-4 andsodium–glucose cotransporter-2 inhibitors, respectively, for the treatment of type 2 diabetes has widely been issued in hospitals. However, the development of double-layered tablets requires simultaneous quantitative dissolution tests that are significantly efficient and cost-effective.

Objective: Individual analysis of the two active pharmaceutical ingredients (APIs) incurs more than twice the time and cost. Consequently, this study aimed to develop a dissolution analysis method that simultaneously quantifies the APIs dapagliflozin and sitagliptin in multi- layered tablets. This simultaneous quantitative dissolution analysis can dramatically reduce analysis time and cost.

Methods: For reversed-phase high-performance liquid chromatography (RP-HPLC) analysis using ultraviolet detection, a Zorbax C18 column (4.6 × 150 mm, 5 μm) was used, and the flow rate was 1.5 mL/min, injection amount 20 μL, and maximum absorption wavelength set to 205 nm. Additionally, the analysis time was set to 1.5 times the retention time of dapagliflozin.

Results: The retention times of dapagliflozin and sitagliptin were 11.57 and 2.56 min, respectively. Further, their relative standard deviations were 0.11% and 0.05%, respectively. Quantitative analysis using RP-HPLC confirmed no peak interference between the APIs and excipients. Both APIs exhibited linearity at a 20–120% concentration.

Conclusion: The dissolution method developed in this study can quantify both APIs simultaneously, thereby reducing analysis time and cost by more than 50% and increasing efficiency in the pharmaceutical industry.

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[1]
Sheth, M.S.; Castle, D.J.; Wang, W.; Lee, A.; Jenkins, Z.M.; Hawke, L.D. Changes to coping and its relationship to improved wellbeing in the optimal health program for chronic disease. SSM - Mental Health,  2023, 3, 100190.
 [http://dx.doi.org/10.1016/j.ssmmh.2023.100190]

[2]
Chen, L.; Zhang, J.; Sun, Y.; Zhao, Y.; Liu, X.; Fang, Z.; Feng, L.; He, B.; Zou, Q.; Tracey, G.J. A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity. Nat. Commun.,  2023, 14(1), 1405.
 [http://dx.doi.org/10.1038/s41467-023-36946-7] [PMID:  36918550]

[3]
Terao, N. A qualitative study of blood glucose and side effect self-management among patients with type 2 diabetes undergoing chemotherapy for cancer. Asia Pac. J. Oncol. Nurs.,  2023, 10(2), 100172.
 [http://dx.doi.org/10.1016/j.apjon.2022.100172] [PMID:  36632446]

[4]
Lee, H.; Lee, M.; Park, G.; Khang, A.R. Prevalence of chronic diabetic complications in patients with type 2 diabetes mellitus: A retrospective study based on the national health insurance service-national health screening cohort in Korea, 2002~2015. Korean J. Adult Nurs.,  2022, 34(1), 39-50.
 [http://dx.doi.org/10.7475/kjan.2022.34.1.39]

[5]
Sami, W.; Ansari, T.; Butt, N.S.; Hamid, M.R.A. Effect of diet on type 2 diabetes mellitus: A review. Int. J. Health Sci.,  2017, 11(2), 65-71.
 [PMID:  28539866]

[6]
Sanchez-Rangel, E.; Inzucchi, S.E. Metformin: Clinical use in type 2 diabetes. Diabetologia,  2017, 60(9), 1586-1593.
 [http://dx.doi.org/10.1007/s00125-017-4336-x] [PMID:  28770321]

[7]
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet,  1998, 352(9131), 854-865.
 [http://dx.doi.org/10.1016/S0140-6736(98)07037-8] [PMID:  9742977]

[8]
Yoon, K.H.; Lee, J.H.; Kim, J.W.; Cho, J.H.; Choi, Y.H.; Ko, S.H.; Zimmet, P.; Son, H.Y. Epidemic obesity and type 2 diabetes in Asia. Lancet,  2006, 368(9548), 1681-1688.
 [http://dx.doi.org/10.1016/S0140-6736(06)69703-1] [PMID:  17098087]

[9]
Plosker, G.L. Dapagliflozin. Drugs,  2012, 72(17), 2289-2312.
 [http://dx.doi.org/10.2165/11209910-000000000-00000] [PMID:  23170914]

[10]
Chang, Y.K.; Choi, H.; Jeong, J.Y.; Na, K.R.; Lee, K.W.; Lim, B.J.; Choi, D.E. Dapagliflozin, SGLT2 inhibitor, attenuates renal ischemia-reperfusion injury. PLoS One,  2016, 11(7), e0158810.
 [http://dx.doi.org/10.1371/journal.pone.0158810] [PMID:  27391020]

[11]
Debata, J.; Kumar, S.; Jha, S.K.; Khan, A. A new RP-HPLC method development and validation of dapagliflozin in bulk and tablet dosage form. Int. J. Drug Dev. Res.,  2017, 9(2), 48-51.

[12]
Pathak, S.; Mishra, P. A review on analytical methods of dapagliflozin: An update. Int. J. Pharm. Qual. Assur.,  2020, 11(3), 355-360.
 [http://dx.doi.org/10.25258/ijpqa.11.3.9]

[13]
Suma, B.V.; R, D.; Shenoy, P. A new high-performance thin layer chromatographic method development and validation of dapagliflozin in bulk and tablet dosage form. Int. J. Pharm. Pharm. Sci.,  2019, 11(8), 58-63.
 [http://dx.doi.org/10.22159/ijpps.2019v11i8.34339]

[14]
Skow, M.A.; Bergmann, N.C.; Knop, F.K. Diabetes and obesity treatment based on dual incretin receptor activation: ‘twincretins’. Diabetes Obes. Metab.,  2016, 18(9), 847-854.
 [http://dx.doi.org/10.1111/dom.12685] [PMID:  27160961]

[15]
Qassas, MK; Ameral-mardini, M; Ghazal, H A validated HPLC stability indicating method for the determination of sitagliptin in bulk drug substance and tablets. Int. J. Pharm. Sci. Rev. Res.,  2015, 32(1), 33,194-19.

[16]
Kim, G.W.; Kim, J.H.; Lee, M.Y.; Shin, J.Y.; Shin, Y.G.; Ha, E.H.; Chung, C.H. Factors influencing glycemic control response of sitagliptin. J. Korean Diabetes,  2013, 14(4), 206-211.
 [http://dx.doi.org/10.4093/jkd.2013.14.4.206]

[17]
Satoh-Asahara, N.; Sasaki, Y.; Wada, H.; Tochiya, M.; Iguchi, A.; Nakagawachi, R.; Odori, S.; Kono, S.; Hasegawa, K.; Shimatsu, A. A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients. Metabolism,  2013, 62(3), 347-351.
 [http://dx.doi.org/10.1016/j.metabol.2012.09.004] [PMID:  23062489]

[18]
Pratley, R.E.; Kipnes, M.S.; Fleck, P.R.; Wilson, C.; Mekki, Q.; Group, A.S. Efficacy and safety of the dipeptidyl peptidase‐4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes Obes. Metab.,  2009, 11(2), 167-176.
 [http://dx.doi.org/10.1111/j.1463-1326.2008.01016.x] [PMID:  19125778]

[19]
Sorli, C.; Heile, M.K. Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J. Multidiscip. Healthc.,  2014, 7, 267-282.
 [http://dx.doi.org/10.2147/JMDH.S64084] [PMID:  25061317]

[20]
Min, S.H.; Yoon, J.H.; Hahn, S.; Cho, Y.M. Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: A systematic review with indirect comparison meta‐analysis. Diabetes Metab. Res. Rev.,  2017, 33(1), e2818.
 [http://dx.doi.org/10.1002/dmrr.2818] [PMID:  27155214]

[21]
Li, D.; Shi, W.; Wang, T.; Tang, H. SGLT2 inhibitor plus DPP‐4 inhibitor as combination therapy for type 2 diabetes: A systematic review and meta‐analysis. Diabetes Obes. Metab.,  2018, 20(8), 1972-1976.
 [http://dx.doi.org/10.1111/dom.13294] [PMID:  29573110]

[22]
Acheampong, A.; Gyasi, W.O.; Darko, G.; Apau, J.; Addai-Arhin, S. Validated RP-HPLC method for simultaneous determination and quantification of chlorpheniramine maleate, paracetamol and caffeine in tablet formulation. Springerplus,  2016, 5(1), 625.
 [http://dx.doi.org/10.1186/s40064-016-2241-2] [PMID:  27330891]

[23]
Lavanya, R.; Yunoos, M.; Pradesh, A. Development and validation of RP-HPLC method for the estimation of sitagliptin phosphate in bulk and its tablet dosage form. J. Adv. Pharm. Educ. Res.,  2013, 3(4)

[24]
Rahman, N.; Azmi, S.N.H.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: An integrated approach. Accredit. Qual. Assur.,  2006, 11(1-2), 69-74.
 [http://dx.doi.org/10.1007/s00769-006-0095-y]

[25]
Sharma, S.; Goyal, S.; Chauhan, K. A review on analytical method development and validation. Int. J. Appl. Pharm.,  2018, 10(6), 8-15.
 [http://dx.doi.org/10.22159/ijap.2018v10i6.28279]

[26]
Punagoti, R.A.; Mourya, R. Development and validation of new RP-HPLC method for the quantitative estimation of sitagliptin phosphate in bulk and tablet dosage form. Int. J. Adv. Sci. Res.,  2021, 12(03), 301-305.

[27]
Mercier-Letondal, P.; Marton, C.; Godet, Y.; Galaine, J. Validation of a method evaluating T cell metabolic potential in compliance with ICH Q2 (R1). J. Transl. Med.,  2021, 19(1), 21.
 [http://dx.doi.org/10.1186/s12967-020-02672-7] [PMID:  33407568]

[28]
Vidushi, Y.; Meenakshi, B.; Bharkatiya, M. A review on HPLC method development and validation. Res. J. Life Sci. Bioinform. Pharm. Chem. Sci.,  2017, 2(6), 178.

[29]
Krishnaiah, C.; Reddy, A.R.; Kumar, R.; Mukkanti, K. Stability-indicating UPLC method for determination of Valsartan and their degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms. J. Pharm. Biomed. Anal.,  2010, 53(3), 483-489.
 [http://dx.doi.org/10.1016/j.jpba.2010.05.022] [PMID:  20646890]

[30]
Sahu, P.K.; Ramisetti, N.R.; Cecchi, T.; Swain, S.; Patro, C.S.; Panda, J. An overview of experimental designs in HPLC method development and validation. J. Pharm. Biomed. Anal.,  2018, 147, 590-611.
 [http://dx.doi.org/10.1016/j.jpba.2017.05.006] [PMID:  28579052]

[31]
Bhardwaj, S.K.; Dwivedia, K.; Agarwala, D. A review: HPLC method development and validation. Int J. Anal. Bioanal. Chem.,  2015, 5(4), 76-81.

[32]
Tache, F.; Albu, M. Specificity of an analytical HPLC assay method of metformin hydrochloride. Rev. Roum. Chim.,  2007, 52(6), 603-609.

[33]
Araujo, P. Key aspects of analytical method validation and linearity evaluation. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2009, 877(23), 2224-2234.
 [http://dx.doi.org/10.1016/j.jchromb.2008.09.030] [PMID:  18929516]

[34]
Prasad, P.B.N.; Satyanaryana, K.; Krishnamohan, G. Development and validation of a method for simultaneous determination of metformin and saxagliptin in a formulation by RP-HPLC. Am. J. Anal. Chem.,  2015, 6(11), 841-850.
 [http://dx.doi.org/10.4236/ajac.2015.611080]

[35]
Ermer, J.; Arth, C.; De Raeve, P.; Dill, D.; Friedel, H.D.; Höwer-Fritzen, H.; Kleinschmidt, G.; Köller, G.; Köppel, H.; Kramer, M.; Maegerlein, M.; Schepers, U.; Wätzig, H. Precision from drug stability studies. J. Pharm. Biomed. Anal.,  2005, 38(4), 653-663.
 [http://dx.doi.org/10.1016/j.jpba.2005.02.009] [PMID:  15967293]

[36]
Ershadi, S.; Shayanfar, A. Are LOD and LOQ reliable parameters for sensitivity evaluation of spectroscopic methods? J. AOAC Int.,  2018, 101(4), 1212-1213.
 [http://dx.doi.org/10.5740/jaoacint.17-0363] [PMID:  29566782]

[37]
Panchumarthy, RCNN; Pravallika, D ; Sri, DN A review on step-bystep analytical method validation. IOSR J. Pharm.,  2015, 5(10), 07-19.

[38]
Paul, K.; Gowda BH, J.; Shankar, S.J.; Narasimha, R.D. Development and validation of simplified RP-HPLC method for quantification of Darunavir in commercial tablets. Mater. Today Proc.,  2021, 47, 4155-4161.
 [http://dx.doi.org/10.1016/j.matpr.2021.04.444]

[39]
Sankar, A.; Sythana, S.; Jhansi, A.; Shanmugasundharam, P.; Aumithra, M. Development and validation for simultaneous estimation of sitagliptin and metformin in pharmaceutical dosage form using RP-HPLC method. Int. J. Pharm. Tech. Res.,  2013, 5(4), 1736-1744.

[40]
Dongala, T.; Katari, N.K.; Palakurthi, A.K.; Jonnalagadda, S.B. Development and validation of a generic RP‐HPLC PDA method for the simultaneous separation and quantification of active ingredients in cold and cough medicines. Biomed. Chromatogr.,  2019, 33(11), e4641.
 [http://dx.doi.org/10.1002/bmc.4641] [PMID:  31265736]

[41]
Gustavo, G.A.; Herrador, A.M. A practical guide to analytical method validation, including measurement uncertainty and accuracy profiles. Trends Analyt. Chem.,  2007, 26(3), 227-238.
 [http://dx.doi.org/10.1016/j.trac.2007.01.009]

[42]
Guideline, I.C.H. Validation of analytical procedures Q2 (R2); ICH: Geneva, Switzerland, 2022. 

[43]
Geetha, G.; Raju, K.N.G.; Kumar, B.V.; Raja, M.G. Analytical method validation: An updated. Int. J. Pharma Bio Sci.,  2012, 1, 64-71.

[44]
Shabir, G.A.; John Lough, W.; Arain, S.A.; Bradshaw, T.K. Evaluation and application of best practice in analytical method validation. J. Liq. Chromatogr. Relat. Technol.,  2007, 30(3), 311-333.
 [http://dx.doi.org/10.1080/10826070601084753]

[45]
Jahan, M.S.; Islam, M.J.; Begum, R.; Kayesh, R.; Rahman, A. A study of method development, validation, and forced degradation for simultaneous quantification of paracetamol and ibuprofen in pharmaceutical dosage form by RP-HPLC method. Anal. Chem. Insights,  2014, 9, 75-81.
 [PMID:  25452691]

[46]
Shabir, G.A. Method development and validation for the GC–FID assay of p-cymene in tea tree oil formulation. J. Pharm. Biomed. Anal.,  2005, 39(3-4), 681-684.
 [http://dx.doi.org/10.1016/j.jpba.2005.03.036] [PMID:  15935601]

[47]
Broadhurst, D.; Goodacre, R.; Reinke, S.N.; Kuligowski, J.; Wilson, I.D.; Lewis, M.R.; Dunn, W.B. Guidelines and considerations for the use of system suitability and quality control samples in mass spectrometry assays applied in untargeted clinical metabolomic studies. Metabolomics,  2018, 14(6), 72.
 [http://dx.doi.org/10.1007/s11306-018-1367-3] [PMID:  29805336]

[48]
Stauffer, M. Calibration and validation of analytical methods: A sampling of current approachesIn: BoD–Books on Demand; Intechopen, 2018. 

[49]
Gallo, P.; Di Marco, P.I.; Esposito, F.; Fasano, E.; Scognamiglio, G.; Mita, G.D.; Cirillo, T. Determination of BPA, BPB, BPF, BADGE and BFDGE in canned energy drinks by molecularly imprinted polymer cleaning up and UPLC with fluorescence detection. Food Chem.,  2017, 220, 406-412.
 [http://dx.doi.org/10.1016/j.foodchem.2016.10.005] [PMID:  27855918]

[50]
Viswanathan, C.T.; Bansal, S.; Booth, B.; DeStefano, A.J.; Rose, M.J.; Sailstad, J.; Shah, V.P.; Skelly, J.P.; Swann, P.G.; Weiner, R. Quantitative bioanalytical methods validation and implementation: Best practices for chromatographic and ligand binding assays. Pharm. Res.,  2007, 24(10), 1962-1973.
 [http://dx.doi.org/10.1007/s11095-007-9291-7] [PMID:  17458684]

[51]
Stöckl, D.; D’Hondt, H.; Thienpont, L.M. Method validation across the disciplines—Critical investigation of major validation criteria and associated experimental protocols. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2009, 877(23), 2180-2190.
 [http://dx.doi.org/10.1016/j.jchromb.2008.12.056] [PMID:  19157996]

[52]
Van Eeckhaut, A.; Lanckmans, K.; Sarre, S.; Smolders, I.; Michotte, Y. Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2009, 877(23), 2198-2207.
 [http://dx.doi.org/10.1016/j.jchromb.2009.01.003] [PMID:  19179125]

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Development and Validation of Simultaneous Quantitative Dissolution Analysis for the Two Active Pharmaceutical Ingredients in Dapagliflozin Propanediol Monohydrate-sitagliptin Phosphate Monohydrate Multi-layered Tablets

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