Formulation and Evaluation of Buccoadesive Tablets of Nateglinide

Abstract

The present study focuses on the formulation and evaluation of buccoadhesive tablets of Nateglinide, an oral antidiabetic drug used in the management of type 2 diabetes mellitus. Due to its short half-life and extensive first-pass metabolism, buccal delivery offers an alternative route to improve bioavailability. Buccoadhesive tablets were prepared using different polymers such as HPMC, Carbopol, and sodium CMC by direct compression method. The prepared formulations were evaluated for physicochemical parameters, swelling index, drug content uniformity, and in-vitro drug release. The results indicated that the optimized formulation showed satisfactory adhesion, controlled drug release, and improved drug availability, suggesting buccal delivery as a promising approach for Nateglinide administration.

Introduction

This study focuses on the development and evaluation of mucoadhesive buccal tablets of Nateglinide to improve the treatment of Type 2 Diabetes Mellitus. Nateglinide is an effective short-acting antidiabetic drug, but its therapeutic use is limited by extensive first-pass metabolism, low bioavailability, short half-life (approximately 1.5 hours), and the need for frequent dosing. Buccal drug delivery was proposed as an alternative route to bypass hepatic metabolism, enhance bioavailability, provide sustained drug release, and improve patient compliance.

The tablets were formulated using Carbopol 934P, HPMC K4M, and Sodium CMC as mucoadhesive and release-controlling polymers through the direct compression method. Eight formulations (F1–F8) with different polymer ratios were prepared and evaluated for physicochemical properties including weight variation, hardness, thickness, friability, drug content, surface pH, swelling index, and in vitro drug release.

All formulations met pharmacopoeial quality standards, exhibiting:

• Uniform tablet weight and thickness.
• Adequate hardness (5.5–6.7 kg/cm²).
• Friability below 1%, indicating good mechanical strength.
• Drug content within the acceptable range (95–105%).
• Surface pH between 6.6 and 7.2, suggesting compatibility with the buccal mucosa and minimal irritation.

Drug release studies demonstrated sustained release for up to 16 hours, with Formulation F7 showing the best overall performance by achieving approximately 100% drug release with controlled release kinetics. The balanced ratio of Carbopol and HPMC in F7 provided optimal swelling, gel formation, and drug diffusion. In contrast, F3 exhibited a burst release due to lower matrix resistance, while F4 showed the slowest release because of its high Carbopol and low HPMC content.

Release kinetics analysis indicated that drug release followed the Higuchi model, suggesting a diffusion-controlled mechanism, while the Korsmeyer–Peppas model indicated non-Fickian (anomalous) transport, where both diffusion and polymer relaxation contributed to sustained drug release.

Overall, the study concludes that mucoadhesive buccal tablets are a promising alternative to conventional oral Nateglinide formulations, offering enhanced bioavailability, reduced first-pass metabolism, prolonged drug release, fewer dosing requirements, and improved patient compliance. Among all formulations, F7 was identified as the optimized formulation and is recommended for further in vivo studies and potential clinical application.

Conclusion

From the results of the present study, it can be concluded that mucoadhesive buccal tablets of Nateglinide were successfully formulated and evaluated. The developed formulations exhibited satisfactory physicochemical properties and complied with pharmacopoeial specifications. The study confirmed that polymer concentration plays a crucial role in controlling drug release behavior. Among all formulations, F7 was identified as the optimized formulation, as it showed controlled and sustained drug release (~100% in 16 hours) with desirable mechanical properties and stability. The balanced combination of Carbopol and HPMC in F7 contributed to effective gel formation, swelling, and controlled drug diffusion. The in vitro release studies indicated that the formulations followed a diffusion-controlled release mechanism, best described by the Higuchi model. The non-Fickian release behavior suggests that both polymer swelling and drug diffusion are responsible for the sustained release profile. The buccal drug delivery system proved to be a promising alternative to conventional oral dosage forms by: • Enhancing bioavailability • Reducing first-pass metabolism • Providing sustained drug release • Improving patient compliance Thus, the developed formulation offers significant advantages in the management of Type 2 Diabetes Mellitus by maintaining consistent plasma drug levels and reducing dosing frequency. In conclusion, the study successfully achieved its objectives of developing a stable, effective, and patient-friendly sustained release formulation of Nateglinide. The optimized formulation (F7) can be considered a promising candidate for further in vivo studies and potential clinical application.

References

[1] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81–S90. [2] World Health Organization. Global report on diabetes. Geneva: WHO; 2016. [3] Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci. 1998;1(1):15–30. [4] Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005;57(11):1556–1568. [5] Rathbone MJ, Drummond BK, Tucker IG. Oral cavity as a site for systemic drug delivery. Adv Drug Deliv Rev. 1994;13(1–2):1–22. [6] Hollander PA, Schwartz SL, Gatlin MR, Haas SJ, Zheng H. Importance of early insulin secretion: comparison of nateglinide and glyburide. Diabetes Care. 2001;24(6):983–988. [7] Shinkai H. Nateglinide: a novel rapid-acting insulinotropic agent. Drugs Today (Barc). 1999;35(12):895–907. [8] Sweetman SC. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009. [9] Boateng JS, Ayensu I, Pawar H, Tetteh J. Polyox and carrageenan-based buccal delivery systems. J Pharm Sci. 2013;102(2):457–476. [10] Nafee NA, Boraie NA, Ismail FA, Mortada LM. Design and characterization of mucoadhesive buccal patches. AAPS PharmSciTech. 2003;4(4):E49. [11] Peppas NA, Buri PA. Surface, interfacial and molecular aspects of polymer bioadhesion. J Control Release. 1985;2(4):257–275. [12] Laffleur F. Mucoadhesive polymers for buccal drug delivery. Drug Dev Ind Pharm. 2014;40(5):591–598. [13] Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm. 2009;71(3):505–518. [14] Indian Pharmacopoeia Commission. Indian Pharmacopoeia. Ghaziabad: IPC; 2018. [15] Aulton ME, Taylor KM. Aulton’s Pharmaceutics: The Design and Manufacture of Medicines. 4th ed. Elsevier; 2013. [16] Carr RL. Evaluating flow properties of solids. Chem Eng.1965;72:163–168. [17] Hausner HH. Friction conditions in a mass of metal powder. Int J Powder Metall. 1967;3(4):7–13. [18] United States Pharmacopeia. USP 36–NF 31. Rockville: USP Convention; 2013. [19] ICH. Validation of analytical procedures: Q2(R1). Geneva; 2005. [20] Patel VF, Liu F, Brown MB. Advances in oral transmucosal drug delivery. J Control Release. 2011;153(2):106–116. [21] Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery systems: a promising option. Int J Pharm. 2006;321(1–2):1–11. [22] Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Capuccella M, et al. Development of mucoadhesive patches. J Control Release. 2004;99(1):73–82. [23] Gupta A, Garg S, Khar RK. Measurement of bioadhesive strength of mucoadhesive buccal tablets. Indian Drugs. 2007;44(4):270–276. [24] Semalty M, Semalty A, Kumar G. Formulation and characterization of mucoadhesive buccal films. Indian J Pharm Sci. 2008;70(1):43–48. [25] Park H, Robinson JR. Mechanisms of mucoadhesion. Pharm Res. 1987;4(6):457–464. [26] Lehr CM, Bouwstra JA, Schacht EH, Junginger HE. In vitro evaluation of mucoadhesiveproperties. Pharm Res. 1992;9(1):70–75. [27] Ponchel G, Irache JM. Specific and non-specific bioadhesive particulate systems. Int J Pharm. 1998;157(1):11–24. [28] Mortazavi SA, Smart JD. An investigation into the role of water movement. Int J Pharm. 1995;124(2):173–182. [29] Khanna R, Agarwal SP, Ahuja A. Preparation and evaluation of buccal tablets. Indian Drugs. 1997;34(5):299–305. [30] Smart JD. Buccal drug delivery. Expert Opin Drug Deliv. 2005;2(3):507–517.

Copyright

Copyright © 2026 Susmitha Pilli, Tamma Kusuma, Meer Hussain Shaik, Doppasani Meenakshi, Birudugadda Lisha, Chamataboina Mounika, Pragallapti Rambabu, V. Bhaskara Raju. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.