Formulation and Evaluation of Buccal Mucoadhesive Bilayer Tablets of Apixaban
Abstract
Background: Apixaban is a factor Xa inhibitor, an anticoagulant; that exhibits low oral bioavailability (around 50%) as a result of its extensive first-pass metabolism, which highlights the need for improved delivery methods.
Aim: This research is carried out to formulate and evaluate a bilayered buccal tablet formulation of Apixaban that adheres to mucosal surfaces.
Materials and Methods: Apixaban was obtained from (NATCO Pharma Limited-Chemical Division, Hyderabad); The specified qualities were achieved in formulations (F1 to F9) by varying the amounts of polymers such as sodium alginate, hydroxypropyl methylcellulose (HPMC K4M), and Carbopol (934p). To make mucoadhesive bilayered buccal tablets, the direct compression method was employed. Tablets were evaluated for physicochemical properties (thickness, weight, hardness, drug content), mucoadhesive strength, in vitro drug release, and stability. Fourier-Transform Infrared (FTIR) spectroscopy assessed drug-excipient compatibility.
Results: The optimized formulation (F7), with its 20 mg of Carbopol, was emerged from a series of testing. Excellent drug uniformity (approximately 99%), and strong adhesive properties. Drug release testing showed nearly 88% release within 180 minutes, following the first-order and Higuchi diffusion model (R² = 0.9904). FTIR confirmed no drug-excipient interactions, and stability studies at 40 °C / 75 % RH demonstrated physical and chemical integrity over three months.
Conclusion: The formulated buccal mucoadhesive bilayer tablets provide a potentially effective, non-invasive route for apixaban administration that circumvents hepatic metabolism and enhance bioavailability.
Keywords: Apixaban, Bilayered Buccal Tablet, Mucoadhesion, Direct compression method, Carbopol.
Keywords:
Apixaban, Bilayered Buccal Tablet, Mucoadhesion, Direct compression method, CarbopolDOI
https://doi.org/10.22270/jddt.v15i12.7466References
1. Shirsand SB, Shivakumar HG, Hiremath SN, Suresh S, Venkatesh YP. Formulation and optimization of mucoadhesive bilayer tablets of atenolol. DARU Journal of Pharmaceutical Sciences. 2012;20(1):72. https://doi.org/10.4103/2230-973X.96924 PMid:23071958 PMCid:PMC3465156
2. Shital S, Bhanudas R. Mucoadhesive buccal drug delivery: An overview. J Adv Pharm Educ Res. 2013;3(4):319-26.
3. Salamat-Miller N, Chittchang M, Johnston TP. The use of mucoadhesive polymers in buccal drug delivery. Advanced Drug Delivery Reviews. 2005;57(11):1666-1691. https://doi.org/10.1016/j.addr.2005.07.003 PMid:16183164
4. Reddy PC, Chaitanya KS, Rao YM. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. DARU Journal of Pharmaceutical Sciences. 2011;19(6):385-397.
5. Mehta Y, Bhatt DL. A review of venous thromboembolism risk assessment models. Thrombosis Journal. 2023;21(1):122.
6. Mackman N. New insights into the mechanisms of venous and arterial thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2020;40(5):1014-1023.
7. Byon W, Garonzik S, Boyd RA, Frost CE. Apixaban: a clinical pharmacokinetic and pharmacodynamic review. Clinical Pharmacokinetics. 2019;58(10):1265-1279. https://doi.org/10.1007/s40262-019-00775-z PMid:31089975 PMCid:PMC6769096
8. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992. https://doi.org/10.1056/NEJMoa1107039 PMid:21870978
9. Baka E, Comer JEA, Takács-Novák K. Study of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound. J Pharm Biomed Anal. 2008;46(2):335-41. https://doi.org/10.1016/j.jpba.2007.10.030 PMid:18055153
10. Giron D. Thermal analysis of drugs and drug products. J Pharm Biomed Anal. 1995;11(11-12):1185-92.
11. SG, Mohite SK. Development and validation of UV spectrophotometric method for estimation of Apixaban in bulk and tablet dosage form. Int J Pharm Sci Res. 2014;5(4):1363-67.
12. Sireesha K, Reddy BP, Rani AP. UV spectrophotometric method development and validation for the determination of Apixaban in bulk and tablet dosage form. Asian J Pharm Clin Res. 2018;11(10):258-61.
13. Singh A, Sharma PK, Garg VK, Garg G. Compatibility studies by FT-IR spectroscopy between losartan potassium and excipients used in the development of tablet formulations. Int J Pharm Pharm Sci. 2011;3(3):189-91.
14. Muralidharan S, Kumar V. FTIR and compatibility studies of montelukast sodium with excipients used in the formulation of tablets. Int J Pharm Pharm Sci. 2013;5(2):352-57.
15. Borgaonkar PA, Shinde J, Jadhav S. Formulation and evaluation of bilayer buccal tablets of zolmitriptan. J Pharm Res Int. 2021;33(33B):34-42.
16. Patel VM, Prajapati BG, Patel MM. Formulation, evaluation and comparison of bilayered and multilayered buccal devices of propranolol hydrochloride. AAPS PharmSciTech. 2007;8(1):E147-53. https://doi.org/10.1208/pt0801022 PMid:17408221 PMCid:PMC2750433
17. United States Pharmacopeia. Weight variation test for tablets. USP 41-NF 36. Rockville (MD): United States Pharmacopeial Convention; 2018. p. 6741-6742.
18. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. Vol. I. Ghaziabad: IPC; 2022. General Chapter: Tablets - Evaluation Tests; p. 877-878.
19. United States Pharmacopeia. USP 43-NF 38. Rockville (MD): United States Pharmacopeial Convention; 2020. General Chapter <705> Quality Tests - Tablets; p. 5125-5126.
20. British Pharmacopoeia Commission. British Pharmacopoeia. Vol. I. London: TSO (The Stationery Office); 2020. General Monograph - Tablets; p. A380-A381.
21. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. Vol. I. Ghaziabad: IPC; 2022. General Chapter: Tablets - Evaluation Tests; p. 881-883.
22. British Pharmacopoeia Commission. British Pharmacopoeia. Vol. I. London: TSO; 2020. General Monograph - Tablets; p. A382-A383.
23. United States Pharmacopeia. USP 43-NF 38. Rockville (MD): United States Pharmacopeial Convention; 2020. General Chapter <1217> Tablet Breaking Force; p. 6732-6734.
24. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. Vol. I. Ghaziabad: IPC; 2022. General Chapter: Tablets - Friability; p. 885-886.
25. British Pharmacopoeia Commission. British Pharmacopoeia. Vol. I. London: TSO; 2020. General Monograph - Tablets; p. A384-A385.
26. United States Pharmacopeia. USP 43-NF 38. Rockville (MD): United States Pharmacopeial Convention; 2020. General Chapter <1216> Tablet Friability; p. 6728-6730.
27. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. Vol. I. Ghaziabad: IPC; 2022. General Monograph - Tablets: Assay / Uniformity of Content; p. 893-895
28. Patel VM, Prajapati BG, Patel MM. Design and evaluation of a mucoadhesive drug delivery system for systemic delivery of propranolol hydrochloride. AAPS PharmSciTech. 2007;8(3):E119-26. https://doi.org/10.1208/pt0802045 PMid:17622120 PMCid:PMC2750360
29. Patel VM, Prajapati BG, Patel MM. Design and evaluation of a mucoadhesive drug delivery system for systemic delivery of propranolol hydrochloride. AAPS PharmSciTech. 2007;8(3):E119-26. https://doi.org/10.1208/pt0802045 PMid:17622120 PMCid:PMC2750360
30. Borges AF, Silva C, Coelho JFJ, Simões S. Oral mucoadhesive drug delivery systems-A review of mucoadhesion theories and testing methods. Carbohydr Polym. 2015;117:667-81.
31. Reddy PV, Murthy TEGK, Reddy SC. Buccal drug delivery using mucoadhesive tablets: Development and evaluation of propranolol hydrochloride tablets. Indian J Pharm Sci. 2002;64(4):343-8.
32. Bhupinder B, Singh SK, Rana AC, Gupta GD. Formulation and evaluation of mucoadhesive buccal tablets of metoprolol tartrate. Int J Drug Dev Res. 2012;4(2):147-61.
33. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217-23.
34. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-33. https://doi.org/10.1016/S0928-0987(01)00095-1 PMid:11297896
35. Indian Pharmacopoeia Commission. Indian Pharmacopoeia, Vol. I. Stability testing of active pharmaceutical ingredients and finished pharmaceutical products. Ghaziabad: IPC; 2022. p. 112-118.
36. The United States Pharmacopeial Convention. United States Pharmacopeia and National Formulary (USP-NF). General chapter <1225> - Stability considerations in dispensing practice. Rockville, MD; 2022. p. 8756-8764.
37. Medicines and Healthcare products Regulatory Agency. British Pharmacopoeia, Vol. I. Stability of pharmaceutical products. London: MHRA; 2023. p. A325-A333
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