Advances and Challenges in Buccal Drug Delivery Systems: A Comprehensive Review of Mucoadhesive Technologies, Novel Formulations, and Clinical Applications
Keywords:
Buccal drug delivery, Mucoadhesive polymers, Nanocarriers, Smart drug delivery systems, Controlled releaseAbstract
Buccal drug delivery offers a non-invasive route that bypasses first-pass metabolism and enhances patient compliance. This review highlights recent progress in mucoadhesive polymers, including both traditional and stimuli-responsive materials that improve drug retention and controlled release. Various dosage forms such as tablets, films, sprays, and advanced systems like microneedles and nanofibers are examined for their design and clinical potential. Nanocarrier integration has expanded buccal delivery to include peptides, proteins, and nucleic acids. Key challenges—such as enzymatic degradation, limited permeability, and patient adherence—are discussed alongside regulatory and market considerations. Future directions point toward smart, personalized systems and AI-driven formulation strategies.
References
1. Parmar HG, Jain JJ, Patel TK, Patel VM. Buccal patch: A technical note. Int J Pharm Sci Rev Res. 2010;4:2010.
2. Rossi S, Sandri G, Caramella CM. Buccal drug delivery: a challenge already won? Drug Discov Today Technol. 2005;2:59–65.
3. Patel VF, Liu F, Brown MB. Modeling the oral cavity: in vitro and in vivo evaluations of buccal drug delivery systems. J Control release. 2012;161:746–56.
4. Laffleur F. Mucoadhesive polymers for buccal drug delivery. Drug Dev Ind Pharm. 2014;40:591–8.
5. Rao NGR, Shravani B, Reddy MS. Overview on buccal drug delivery systems. J Pharm Sci Res. 2013;5:80.
6. Patel VM, Prajapati BG, Patel MM. Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharm. 2007;57:61–72.
7. Okeke OC, Boateng JS. Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy. Int J Biol Macromol. 2016;91:31–44.
8. Pamlényi K, Kristó K, Sovány T, Regdon Jr G. Development and evaluation of bioadhesive buccal films based on sodium alginate for allergy therapy. Heliyon. 2022;8.
9. Jaipakdee N, Pongjanyakul T, Limpongsa E. Preparation and characterization of poly (vinyl alcohol)-poly (vinyl pyrrolidone) mucoadhesive buccal patches for delivery of lidocaine HCL. Int J Appl Pharm. 2018;10:115–23.
10. Shirvan AR, Bashari A, Hemmatinejad N. New insight into the fabrication of smart mucoadhesive buccal patches as a novel controlled-drug delivery system. Eur Polym J. 2019;119:541–50.
11. Yu Y, Cheng Y, Tong J, Zhang L, Wei Y, Tian M. Recent advances in thermo-sensitive hydrogels for drug delivery. J Mater Chem B. 2021;9:2979–92.
12. Liu L, Yao W, Rao Y, Lu X, Gao J. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms. Drug Deliv. 2017;24:569–81.
13. Smart JD. Buccal drug delivery. Expert Opin Drug Deliv. 2005;2:507–17.
14. Osouli-Bostanabad K, Puliga S, Serrano DR, Bucchi A, Halbert G, Lalatsa A. Microfluidic manufacture of lipid-based nanomedicines. Pharmaceutics. 2022;14:1940.
15. Kaur N, Nirmala SL, Kumar H. A review on study of buccal patches: current status of formulation and evaluation methods. J Drug Deliv Ther. 2014;4:69–79.
16. Okur NÜ, Bülbül EÖ, Yağcılar AP, Siafaka PI. Current status of mucoadhesive gel systems for buccal drug delivery. Curr Pharm Des. 2021;27:2015–25.
17. Caffarel-Salvador E, Kim S, Soares V, Tian RY, Stern SR, Minahan D, et al. A microneedle platform for buccal macromolecule delivery. Sci Adv. 2021;7:eabe2620.
18. Desai DD, Manikkath J, Lad H, Kulkarni M, Manikkath A, Radhakrishnan R. Nanotechnology-based mucoadhesive and mucus-penetrating drug-delivery systems for transbuccal drug delivery. Nanomedicine. 2023;18:1495–514.
19. Abd El Azim H, Nafee N, Ramadan A, Khalafallah N. Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins. Int J Pharm. 2015;488:78–85.
20. Jin Y, Wen J, Garg S, Liu D, Zhou Y, Teng L, et al. Development of a novel niosomal system for oral delivery of Ginkgo biloba extract. Int J Nanomedicine. 2013;421–30.
21. Ma P, Si X, Chen Q, Ma L, Hou M, Xu Z, et al. Oral drug delivery systems for ulcerative colitis therapy: A comparative study with microparticles and nanoparticles. Curr Cancer Drug Targets. 2019;19:304–11.
22. Shelley H, Babu RJ. Role of cyclodextrins in nanoparticle-based drug delivery systems. J Pharm Sci. 2018;107:1741–53.
23. Singh AK, Sharma AK, Khan I, Gothwal A, Gupta L, Gupta U. Oral drug delivery potential of dendrimers. Nanostructures Oral Med. Elsevier; 2017. p. 231–61.
24. Sankar V, Hearnden V, Hull K, Juras DV, Greenberg MS, Kerr AR, et al. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis. 2011;17:73–84.
25. Chen F-M, An Y, Zhang R, Zhang M. New insights into and novel applications of release technology for periodontal reconstructive therapies. J Control release. 2011;149:92–110.
26. Gevirtz C. Fentanyl Face-Off: Fentora Versus Actiq. Top Pain Manag. 2008;23:1–5.
27. Sharma S, Prasad A, Nehru R, Anand KS, Rishi RK, Chaturvedi S, et al. Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine. Headache J Head Face Pain. 2002;42:896–902.
28. Caon T, Jin L, Simões CMO, Norton RS, Nicolazzo JA. Enhancing the buccal mucosal delivery of peptide and protein therapeutics. Pharm Res. 2015;32:1–21.
29. Uddin MN, Allon A, Roni MA, Kouzi S. Overview and future potential of fast dissolving buccal films as drug delivery system for vaccines. J Pharm Pharm Sci. 2019;22:388–406.
30. Wening K, Breitkreutz J. Oral drug delivery in personalized medicine: unmet needs and novel approaches. Int J Pharm. 2011;404:1–9.
31. Patil PP, Pawar AP, Mahadik KR, Gaikwad VL. An overview of regulations for bioequivalence assessment of locally acting orally inhaled drug products for the United States, Europe, Canada, and India. Expert Opin Drug Deliv. 2021;18:1843–55.
32. Reddy PC, Chaitanya KSC, Rao YM. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. DARU J Pharm Sci. 2011;19:385.
33. Kumar A, Kumar A. Smart pharmaceutical formulations of biopolymeric materials in buccal drug delivery. Biomed Mater Devices. 2024;1–9.
34. Vllasaliu D, Thanou M, Stolnik S, Fowler R. Recent advances in oral delivery of biologics: nanomedicine and physical modes of delivery. Expert Opin Drug Deliv. 2018;15:759–70.
