Bi-layer tablets of sitagliptin phosphate & metformin hydrochloride – preparation and evaluation
DOI:
https://doi.org/10.56782/pps.318Keywords:
Bi-layer tablet, immediate release, sustained release, factorial designAbstract
Bi-layer tablets with sitagliptin phosphate as a Immediate Release (IR) layer and metformin HCl as a Sustained Release (SR) layer were developed for hypoglycemic control. The IR formulations were formulated using Aegle marmelos gum (natural antidiabetic agent and disintegrant) by direct compression method and was found to have good pre- and post-compression properties. Disintegeration time for SP3 (2.5 mg of gum) was found to be 128 seconds. Among the IR formulations, SP3 drug release was found to be 99.31% within 10 minutes, aligning with the marketed product Januvia. For sustained release layer optimization, 3² full factorial design was used to study the effects of sustained release polymers X1 - calcium starch (matrix forming polymer) and X2 - HPMC K100 on drug release of metformin at 1, 6, and 12 hours. Metformin SR layer was evaluated for weight variation, hardness, friability and dissolution. MF7 was selected as optimized formulation by factorial design and it achieved 98.52% release over 12 hours similar to marketed product Glycomet. Sustained drug release followed first-order kinetics (R2 = 0.9832) with non-Fickian diffusion (n = 0.765). Further bi-layer tablets were punched and characterized. Bi-layer tablet having MF7 and SP3 as sustained and immediate release layer was considered as optimized and evaluated. Immediate IR layer from the bi-layer tablet had shown 96.15% of sitagliptin release in 10 min and Metformin SR layer have sustained drug release 97.16% up to 12 similar to Innovator bilayer tablet (Istamet). Compatibility studies (FT-IR) showed no component interactions. Bi-layer tablet formulation had shown promising release profiles, offering effective glycemic control and improved patient compliance.
Downloads
References
1. Aulton, M.E. Pharmaceutics: The science of dosage form design, 2nd ed.; Churchill Livingstone: Edinburgh, Scotland, 2002; pp. 244-245. 2. Lachman, L.; Lieberman, H.A.; Kanig, J. L. Theory and Practice of Industrial Pharmacy, 3rd Edn; Lippincott Williams & Wilkins: Philadelphia, United States, 1986; pp. 447-448. 3. Preeti, K.; Kasture, PV. Formulation and in vitro evaluation of bilayer tablets of zolpidem tartrate for biphasic drug release. Int. J. Pharmtech. Res. 2011, 3, 1919-1929. 4. Lalita, L.K.; Banerjee, S.K.; Gadhave, M.V.; Gaikwad, D.D.; Gaykar, A.J. Review on bilayer floating tablet. Asian J. Pharm. Res. Dev. 2013, 1, 31–39. 5. Deshpande, R.; Govda, D. V.; Nawaz, M.; Maramwar, N.; Deepak. Bilayer Tablets Emerging Trends: A Review International Journal of Pharmaceutical Sciences and Research 2011, 2(10), 2534-2544. 6. Ballav, C.; Gough, SC.; Safety and efficacy of sitagliptin-metformin in fixed combination for the treatment of type 2 diabetes mellitus. Clinical Medicine Insights: Endocrinology and Diabetes 2013, 6, 25-37. 7. Yedurkar, P.; Dhiman, MK.; Petkar, K.; Sawant, K. Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro, pharmacokinetic and pharmacodynamic investigations. J. of microencapsul. 2012, 29(2), 126-137. 8. Chowdary, K.P.R.; Tripura Sundari, P.; Sailaja, G. Design and evaluation of Gliclazide CR tablets employing calcium starch – a new starch-based polymer. International Journal of Chemical Sciences 2008, 6(3), 1299-1305. 9. Mahdi, A.; Hameed, D.M.; Al Hindawi A.M.; Najm N.H. Spectrophotometric Methods for Estimation of Metformin HCl and Sitagliptin Phosphate Drugs in Bulk and Some Pharmaceutical Preparations. International journal of Drug Delivery Technology 2021, 11(2), 347-350. DOI: 10.25258/ijddt.11.2.19 10. Almaqtari, M.A.; Al-Odaini, N.A.; Alarbagi, F.A.; Al-Maydama, H. Development and validation of a new spectrophotometric method for simultaneous determination of sitagliptin and metformin hydrochloride in tablet pharmaceutical dosage forms using chemometrics technique in comparison with HPLC. Eclética Química 2023, 48(1), 72-94. DOI: 10.26850/1678-4618eqj.v48.1.2023.p.72-94. 11. Sinha, P.; Maurya, M.; Mishra, M.K. Simultaneous Estimation of Sitagliptin Phosphate And Metformin Hydrochloride In Bulk And Tablet Dosage Form By Ftir Spectrophotometric. World Journal of Pharmaceutical Research 2022, 11(9), 1075-1085. DOI: 10.22159/ijcpr.2022v14i2.1963 12. Hossain, M.S.; Jahan, S.; Rahman, S.A.; Rahman, M.; Kumar, D.; Paul, S.; Rajbangshi, J.C. Design expert software assisted development and evaluation of empagliflozin and sitagliptin combination tablet with improved in-vivo anti-diabetic activities. Heliyon 2023, 9(3), Art. No: 14259. DOI: 10.1016/j.heliyon.2023.e14259 13. Nguyen, N.N.; Pham, D.T.; Nguyen, D.T.; Trinh, T.T. Bilayer tablets with sustained-release metformin and immediate-release sitagliptin: preparation and in vitro/in vivo evaluation. Journal of Pharmaceutical Investigation 2021, 51(5), 579-586. DOI: 10.1007/s40005-021-00533-z 14. Yadav, P.K.; Malik, J.; Singh, G.; Kumar, G.P.; Singh, S.P.; Tiwari, A.; Gupta, P. Formulation evaluation and optimisation of bilayer floating tablet that contained repaglinide and glipizide. International Journal of Pharmaceutical Sciences and Drug Analysis 2024, 4(1), 24-36. 15. Gunnam, S.; Chowdary, K.P.R. Formulation and evaluation of lornoxicam floating tablets employing a new modified starch - optimization by 23 factorial design. Pharmacie Globale 2014, 5(3), 1-5. 16. Patel, H.P.; Patel, D.P.; Christian, J.R.; Shah, P.A.; Patel, K.G.; Gandhi, T.R. Box-Behnken Design Assisted Protein Precipitation Optimization for Simultaneous Determination of Metformin Hydrochloride and Alogliptin Benzoate in Plasma along with Pharmacokinetic Application. Indian Journal of Pharmaceutical Sciences 2021, 83(4), 785-793. 17. Fatima, H.; Mohammed, S.; Begum, A. Effect of Croscormellose Sodium in Sustained Release Layer of Valsartan in Bilayer Tablet with Clopidogrel as Immediate Drug Release and Valsartan as Sustained Drug Release. Journal of Drug Delivery and Therapeutics 2023, 13(12), 35-50. DOI: 10.22270/jddt.v13i12.6067 18. Singh, S.; Shinde, R.; Rangari, N.; Gahukar, K.; Ingawale, S. Formulation and evaluation of mouth dissolving tablets of sitagliptin phosphate with enhanced permeability. NeuroQuantology 2022, 20(9), 5091-5098. DOI: 10.14704/nq.2022.20.9.NQ44589 19. Arya, G.; Mamgain, S.; Saxena, A. Formulation and Evaluation of Bilayer Tablets For The Treatment of Diabetes. Educational Administration: Theory and Practice 2024, 30(6), 3437-3445. DOI: 10.53555/kuey.v30i6.5833 20. Pareek, M.; Sharma, V.; Ravindra, N.; Kumawat, S. Formulation and Evaluation of Bilayer Tablet of Metformin HCl and Sitagliptin. International Journal of Health Advancement and Clinical Research (tz) 2024, 2(2), 1-5. 21. Manga, K.; Sudhakar, M.; Meghana, K.; Avanthi, K.; Swathi, G. Formulation and evaluation of bilayered tablets of sustained release metformin HCl and gliclazide. World Journal of Pharmaceutical Sciences 2022, 10(3), 315-24. DOI: 10.54037/wjps.2022.100310 22. Sahu, E.; Darwhekar, G.N. Formulation and evaluation of bilayer tablet of metformin hydrochloride and sitagliptin phosphate using tamarind seed mucilage. Int J Pharm Sci Med. 2020, 5, 1-5. 23. Kaushal, A.; Arora, S.; Sharma, N.; Singh, S. Development of Bilayer Tablet Containing Saxagliptin Immediate Release and Metformin Sustained Release Using Quality by Design Approach. Current Drug Therapy 2021, 16(2), 184-203. DOI: 10.2174/1574885516666210315100848
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Sailaja Gunnam, Sindhura T, Rajeswari Aleti, Monika Nijhawan
This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
How to Cite
