METFORMIN ADORNED BILAYER TABLETS FOR TYPE Ⅱ DIABETES MANAGEMENT: FORMULATION DEVELOPMENT AND CHARACTERIZATION

Atif Khattak; Shefaat Ullah Shah; Pervaiz Akhtar Shah; Sheikh Abdur Rashid; Hashmat Ullah; Hadia Gul; Saima Mahmood; Mudassar Mazher; Rabia Baloch; Sidra Mumtaz

doi:10.53555/jptcp.v31i4.6048

Atif Khattak
Shefaat Ullah Shah
Pervaiz Akhtar Shah
Sheikh Abdur Rashid
Hashmat Ullah
Hadia Gul
Saima Mahmood
Mudassar Mazher
Rabia Baloch
Sidra Mumtaz

Keywords

Diabetes mellitus, bilayer tablet, Carbopol, direct compression, in-vitro drug release

Abstract

Diabetes mellitus is a chronic metabolic disorder and its management requires uninterrupted drug administration, as failure to show the compliance results in fatal consequences. This study was executed to develop, optimize and characterize metformin HCl adorned bilayer tablets which underwent initial burst release in the stomach followed by a sustained release pattern to meet the once daily requirements for patients acceptability. Metformin HCl is scheduled to be taken three times a day due to having reduced half-life of 2-6 h. Therefore, its development into bilayer tablets having both immediate (IR) and sustained release (SR) layers would be clearly beneficial in reducing the frequency of administration as well as patients compliance. The immediate release layer anticipated the initial burst release in the stomach to quickly produce the antidiabetic effect with subsequent persistent extended action generated by controlled release layer. Direct compression method was used to fabricate bilayer tablets of metformin HCl by incorporating numerous polymers (HPMC K4M, carbopol and chitosan) in varied concentrations. The drug and polymeric admixtures were assessed for compatibility through FTIR and results revealed no interactions among the drug and various polymers. The flow parameters were found to be within the acceptable official range. After compression into bilayer tablets different physico -chemical tests were performed. All the tests were found to be consistent with official limits. The results of in-vitro data showed biphasic release pattern with the release from IR layer within 15 minutes and up to 24 h controlled drug release from SR layer. MT3 was chosen as an optimized formulation batch based on the results of in-vitro controlled drug release, physico-chemical tests and stability profiles. Kinetic model fitting of the release data of formulations (MT1-MT9) demonstrated Fickian diffusion mechanism with zero order kinetics (n<0.5). There was no statistical significant difference found for cumulative drug release of IR layer (p>0.05), however, for SR layer a significant difference was observed for the cumulative amount of drug release (p<0.05). Thus, the anticipated results revealed the potential of carbopol polymer for assuring the biphasic release of metformin HCl.

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References

1. Garcia UG, Vicente AB, Jebari S, Sebal AL, Siddiqi H, Uribe KB. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci [Internet]. 2020 Aug 30 [cited 2022 Jun 10];21(17):6275. Available from: https://www.mdpi.com/1422-0067/21/17/6275/htm
2. Lu G, Wu Z, Shang J, Xie Z, Chen C, zhang C. The effects of metformin on autophagy. Biomed Pharmacother. 2021 May 1;137:111286.
3. Sheleme T. Clinical Pharmacokinetics of Metformin. In: Metformin: Pharmacology and Drug Interactions [Internet]. 2021 [cited 2023 Feb 10]. Available from: https://books.google.com.pk/books?hl=en&lr=&id=B69aEAAAQBAJ&oi=fnd&pg=PA39&dq=metformin+is+not+bound+to+plasma+proteins+and+does+not+undergo+hepatic+metabolism,+which+makes+pharmacokinetic+drug+interactions+uncommon&ots=A0IGcVcZS5&sig=DhvN9fsbnMCkf8bMHRnH
4. Kaur G, Grewal J, Jyoti K, Jain UK, Chandra R, Madan J. Oral controlled and sustained drug delivery systems: Concepts, advances, preclinical, and clinical status. In: Drug Targeting and Stimuli Sensitive Drug Delivery Systems. William Andrew Publishing; 2018. p. 567–626.
5. Akhtar M, Jamshaid M, Zaman M, Mirza AZ. Bilayer tablets: A developing novel drug delivery system. J Drug Deliv Sci Technol [Internet]. 2020;60:1–10. Available from: https://doi.org/10.1016/j.jddst.2020.102079
6. Rao AL, Sandhya T, Mahalakshmi PS, Raasi KM, Durga SJSL, Teja N. Formulation and evaluation of sustained release bilayer tablets of losartan potassium. Asian J Pharm. 2021;15(2):268–77.
7. Usnale V, Nadiwade N, Bendsure A. BILAYER TABLET: REVIEW. World J Pharm Res [Internet]. 2017 [cited 2022 Sep 2];6(10):337–57. Available from: www.wjpr.net
8. Panda S, Mishra B, Behera S. Bi-Layer Tablets: An Emerging State of Art Technology in Dosage Form Design. J Adv Nanotechnol its Appl [Internet]. 2021 [cited 2022 Sep 2];3(2):1–14. Available from: https://doi.org/10.5281/zenodo.5515151
9. Li C, Wang J, Wang Y, Gao H, Wei G. Recent progress in drug delivery. Acta Pharm Sin B. 2019 Nov 1;9(6):1145–62.
10. Nguyen NNT, Pham DT, Nguyen DT, Trinh TTL. Bilayer tablets with sustained-release metformin and immediate-release sitagliptin: preparation and in vitro/in vivo evaluation. J Pharm Investig [Internet]. 2021 Sep 1 [cited 2023 Feb 3];51(5):579–86. Available from: https://link.springer.com/article/10.1007/s40005-021-00533-z
11. Patil MB, Maru AD, Bhadane JS. Formulation and Evaluation of Sustained Release Bilayer Matrix Tablet of Glimepiride and Metformin Hydrochloride. Asian J Res Pharm Sci. 2021 Nov 26;11(4):273–9.
12. Kumar SA, Debnath M, Anusha K, Manna K, Rao JS. Studies on Formulation Development and Evaluations on Losartan Floating and Bioadhesive Drug Delivery System. Pakistan J Pharm Res. 2017;3(2):84–98.
13. Patel P, Ahir K, Patel V, Manani L, Patel C. Drug-Excipient compatibility studies: First step for dosage form development. Pharma Innov J [Internet]. 2015 [cited 2022 Jun 26];4(5):14–20. Available from: www.thepharmajournal.com
14. Jatav R, Singh D, Rathore P, Prakash Jain N, Goswami RB, Jatav Students of MPharm R. FORMULATION AND EVALUATION OF FLOATING PELLETS OF AMOXICILLIN TRIHYDRATE FOR ERADICATION OF H.PYLORI. World J Pharm Res [Internet]. 2021 [cited 2023 Feb 14];10(9):1024–47. Available from: www.wjpr.net
15. Hanif M, Shah S, Rasul A, Abbas G, Zaman M, Amjad MW, et al. Enhancement of oral bioavailability of ibandronate through gastroretentive raft forming drug delivery system: In vitro and in vivo evaluation. Int J Nanomedicine [Internet]. 2020 [cited 2023 Feb 10];15:4847–58. Available from: https://www.tandfonline.com/action/journalInformation?journalCode=dijn20
16. Latif MS, Al-Harbi FF, Nawaz A, Rashid SA, Farid A, Al Mohaini M. Formulation and Evaluation of Hydrophilic Polymer Based Methotrexate Patches: In Vitro and In Vivo Characterization. Polymers (Basel) [Internet]. 2022 Mar 24 [cited 2022 Jun 26];14(7):1310. Available from: https://www.mdpi.com/2073-4360/14/7/1310/htm
17. Soni H, Ghulaxe C, Upadhyay S, Pillai S. DEVELOPMENT AND IN VITRO EVALUATION OF AN ORAL FLOATING TABLET OF METRONIDAZOLE. J Drug Deliv Ther. 2018;8(2):83–6.
18. Morkhade DM. Comparative impact of different binder addition methods, binders and diluents on resulting granule and tablet attributes via high shear wet granulation. Powder Technol. 2017 Oct 1;320:114–24.
19. Rehman FU, Farid A, Shah SU, Dar MJ, Rehman AU, Ahmed N, et al. Self-Emulsifying Drug Delivery Systems (SEDDS): Measuring Energy Dynamics to Determine Thermodynamic and Kinetic Stability. Pharmaceuticals. 2022;15(9):1064.
20. Ashish D, Vibhu S. Formulation and Evaluation of Floating Tablet of Thiocolchicoside. Curr Res Pharm Sci [Internet]. 2022 Apr 6 [cited 2022 Oct 21];12(1):59–67. Available from: http://www.crpsonline.com/index.php/crps/article/view/299
21. Israr M, Pugliese N, Farid A, Ghazanfar S, Di Cerbo A, Muzammal M. Preparation and Characterization of Controlled-Release Floating Bilayer Tablets of Esomeprazole and Clarithromycin. Molecules [Internet]. 2022 May 18 [cited 2023 Jan 3];27(10):3242. Available from: https://www.mdpi.com/1420-3049/27/10/3242/htm
22. Mubeen I, Zaman M, Farooq M, Mehmood A, Azeez FK, Rehman W, et al. Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis. Polymers (Basel) [Internet]. 2022 Sep 9 [cited 2023 Jan 3];14(18):3770. Available from: https://www.mdpi.com/2073-4360/14/18/3770/htm
23. Valte YB, Sangale HA, Kathuria HS, Talele SG, Jadhav AG. Formulation and evaluation of gastro retentive extended release formulation of metformin hydrochloride. GSC Adv Res Rev [Internet]. 2020 Feb 28 [cited 2023 Feb 3];2(2):008–17. Available from: https://gsconlinepress.com/journals/index.php/gscarr/article/view/120
24. Sikdar YKKM, Ahamed A, Mahbubul Alam M, Raihan Sarkar M, Sajeeb BK. Formulation and In-vitro Evaluation of Bilayer Tablets of Atenolol and Amlodipine. Bangladesh Pharm J [Internet]. 2019 Jul 21 [cited 2023 Jan 3];22(2):153–69. Available from: https://www.banglajol.info/index.php/BPJ/article/view/42299
25. López KJS, Vásquez SLG, Vásquez YAG, Suárez AIT, Barranco PG, Gutiérrez MLY, et al. Formulation and evaluation of gastroretentive floating tablets of metformin hydrochloride based on effervescence and swelling. Farma J. 2019;4(1):305.
26. Daravath B, Swathi D, Rao BB. Formulation Development and Evaluation of Sustained Release Bioadhesive Bilayered Buccal Tablets of Furosemide. Anal Chem Lett [Internet]. 2017 Mar 4 [cited 2023 Jun 20];7(2):215–27. Available from: https://www.tandfonline.com/doi/abs/10.1080/22297928.2017.1326839
27. Elsayed MMA, Aboelez MO, Mohamed MS, Mahmoud RA, El-Shenawy AA, Mahmoud EA, et al. Tailoring of Rosuvastatin Calcium and Atenolol Bilayer Tablets for the Management of Hyperlipidemia Associated with Hypertension: A Preclinical Study. Pharmaceutics [Internet]. 2022 Aug 4 [cited 2023 Jan 3];14(8):1629. Available from: https://www.mdpi.com/1999-4923/14/8/1629/htm
28. Latif MS, Azad AK, Nawaz A, Rashid SA, Rahman MH, Al Omar SY, et al. Ethyl cellulose and hydroxypropyl methyl cellulose blended methotrexate-loaded transdermal patches: In vitro and ex vivo. Polymers (Basel). 2021;13(20):1–17.
29. Iffat W, Shoaib MH, Yousuf RI, Qazi F, Mahmood ZA, Muhammad IN, et al. Use of Eudragit RS PO, HPMC K100M, Ethyl Cellulose, and Their Combination for Controlling Nicorandil Release from the Bilayer Tablets with Atorvastatin as an Immediate-Release Layer. J Pharm Innov [Internet]. 2022 Jun 1 [cited 2023 Jan 3];17(2):429–48. Available from: https://link.springer.com/article/10.1007/s12247-020-09513-6
30. Naseem F, Shah SU, Rashid SA, Farid A, Almehmadi M, Alghamdi S. Metronidazole Based Floating Bioadhesive Drug Delivery System for Potential Eradication of H. pylori: Preparation and In Vitro Characterization. Polymers (Basel) [Internet]. 2022 Jan 27 [cited 2022 Jan 28];14(3):519. Available from: https://www.mdpi.com/2073-4360/14/3/519/htm
31. Djebbar M, Chaffai N, Bouchal F, Aouf N. Effervescent floating tablets of metformin HCl developed by melt granulation. Part I: Effect of hydrophilic polymer on biopharmaceutical properties. GSC Biol Pharm Sci [Internet]. 2019 Feb 28 [cited 2023 Feb 3];6(2):052–67. Available from: https://gsconlinepress.com/journals/index.php/gscbps/article/view/285
32. Djebbar M, Chaffai N, Bouchal F. Development of Floating Tablets of Metformin HCl by Thermoplastic Granulation. Part II: In Vitro Evaluation of the Combined Effect of Acacia Gum/HPMC on Biopharmaceutical Performances. Adv Pharm Bull [Internet]. 2020 [cited 2023 Feb 3];10(3):399. Available from: /pmc/articles/PMC7335996/
33. Clénet D, Hourquet V, Woinet B, Ponceblanc H, Vangelisti M. A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate. Eur J Pharm Biopharm. 2019 Sep 1;142:334–43.
34. Aanisah N, Wardhana YW, Chaerunisaa AY, Budiman A. Review on Modification of Glucomannan as an Excipient in Solid Dosage Forms. Polymers (Basel) [Internet]. 2022 Jun 23 [cited 2023 Mar 12];14(13):2550. Available from: https://www.mdpi.com/2073-4360/14/13/2550/htm
35. Chang SY, Sun CC. Insights into the effect of compaction pressure and material properties on interfacial bonding strength of bilayer tablets. Powder Technol. 2019 Sep 1;354:867–76.
36. Georgy KR, Farid RM, Latif R, Bendas ER. A new design for a chronological release profile of etodolac from coated bilayer tablets: In-vitro and in-vivo assessment. J Adv Res. 2019 Jan 1;15:37–47.
37. Syed MA, Hanif S, Ain N ul, Syed HK, Zahoor AF, Khan IU, et al. Assessment of Binary Agarose–Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization. Molecules [Internet]. 2022 Oct 18 [cited 2023 Apr 11];27(20):7004. Available from: https://www.mdpi.com/1420-3049/27/20/7004/htm
38. Peddapalli H, Bakshi V, Boggula N. Formulation, in vitro and ex vivo characterization of mucoadhesive buccal tablets for antihypertensive drug. Artic Asian J Pharm Clin Res [Internet]. 2018 [cited 2023 Feb 19];11(8):402–11. Available from: http://dx.doi.org/10.22159/ajpcr.2018.v11i8.26126
39. Koirala S, Nepal P, Ghimire G, Basnet R, Rawat I, Dahal A, et al. Formulation and evaluation of mucoadhesive buccal tablets of aceclofenac. Heliyon [Internet]. 2021 Mar 1 [cited 2023 Apr 11];7(3):e06439. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2405844021005442
40. Mašková E, Kubová K, Raimi-Abraham BT, Vllasaliu D, Vohlídalová E, Turánek J, et al. Hypromellose – A traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery. J Control Release. 2020 Aug 10;324:695–727.
41. Vrettos NN, Roberts CJ, Zhu Z. Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications. Pharmaceutics [Internet]. 2021 Sep 30 [cited 2023 Mar 12];13(10):1591. Available from: https://www.mdpi.com/1999-4923/13/10/1591/htm
42. Kumar G, Jain V, Shende S, Jain P, Gaurav Kumar C. Formulation and evaluation of bilayer tablets of clarithromycin and omeprazole against Helicobacter pylori infection. ~ 407 ~ Pharma Innov J [Internet]. 2019 [cited 2021 Apr 5];8(1):407–12. Available from: www.thepharmajournal.com
43. Vlachou M, Siamidi A, Anagnostopoulou D, Christodoulou E, Bikiaris NN. Modified Release of the Pineal Hormone Melatonin from Matrix Tablets Containing Poly(L-lactic Acid) and Its PLA-co-PEAd and PLA-co-PBAd Copolymers. Polymers (Basel) [Internet]. 2022 Apr 1 [cited 2023 Mar 12];14(8):1504. Available from: https://www.mdpi.com/2073-4360/14/8/1504/htm
44. Altaani BM, Almaaytah AM, Dadou S, Alkhamis K, Daradka MH, Hananeh W. Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation. Pharm Res [Internet]. 2020 Apr 1 [cited 2021 Dec 26];37(4):1–15. Available from: https://link.springer.com/article/10.1007/s11095-020-02793-0

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Published

Apr 30, 2024

DOI https://doi.org/10.53555/jptcp.v31i4.6048

How to Cite

Atif Khattak, Shefaat Ullah Shah, Pervaiz Akhtar Shah, Sheikh Abdur Rashid, Hashmat Ullah, Hadia Gul, Saima Mahmood, Mudassar Mazher, Rabia Baloch, & Sidra Mumtaz. (2024). METFORMIN ADORNED BILAYER TABLETS FOR TYPE Ⅱ DIABETES MANAGEMENT: FORMULATION DEVELOPMENT AND CHARACTERIZATION. Journal of Population Therapeutics and Clinical Pharmacology, 31(4), 1952–1967. https://doi.org/10.53555/jptcp.v31i4.6048

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Vol. 31 No. 4 (2024): JPTCP

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