A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.
1. N. Salamat-Miller, M. Chittchang and T. P. Johnston, The use of mucoadhesive polymers in buccal drug delivery, Adv. Drug Deliv. Rev.57 (2005) 1666–1691; DOI: 10.1016/j.addr.2005.07.003.
2. R. A. Medve, J. Wang and R. Karim, Tramadol and acetaminophen tablets for dental pain, Anesth. Prog.48 (2001) 79–81.
3. B. W. Morrison, S. Christensen, W. Yuan, J. Brown, S. Amlani and B. Seidenberg, Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial, Clin. Ther.21 (1999) 943–953; DOI: 10.1016/S0149-2918(99)80016-2.
4. J. M. Swegle and C. Logemann, Management of common opioid-induced adverse effects, Am. Fam. Physician74 (2006) 1347–1354.
5. I. Bjarnason, J. Hayllar, A. J. Macpherson and A. Russell, Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans, Gastroenterology104 (1993) 1832–1847.
6. A. Sultan, H. J. McQuay, R. A. Moore and S. Derry, Single dose oral flurbiprofen for acute postoperative pain in adults, Cochrane Libr. (2009); DOI: 10.1002/14651858.CD007358.
7. M. Takada, M. Fukusaki, Y. Terao, K. Yamashita, C. Inadomi, M. Takada and K. Sumikawa, Preadministration of flurbiprofen suppresses prostaglandin production and postoperative pain in orthopedic patients undergoing tourniquet inflation, J. Clin. Anesth.19 (2007) 97–100; DOI: 10.1016/j.jclinane.2006.05.028.
8. R. K. Flath, M. L. Hicks, R. A. Dionne and G. B. Pelleu Jr., Pain suppression after pulpectomy with preoperative flurbiprofen, J. Endodont.13 (1987) 339–347; DOI: 10.1016/S0099-2399(87)80116-487.
9. Y. Fujii and Y. Shiga, Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on propofol injection in the hand: a prospective, randomized, double-blind, vehicle-controlled, dose-finding study in Japanese adult surgical patients, Clin. Ther.27 (2005) 588–593; 10.1016/j.clinthera.2005.05.003.
10. P.-L. Lin, S.-Z. Fan, C.-H. Huang, H.-H. Huang, M.-C. Tsai, C.-J. Lin and W.-Z. Sun, Analgesic effect of lidocaine patch 5 % in the treatment of acute herpes zoster: a double-blind and vehicle-controlled study, Region. Anesth. Pain M.33 (2008) 320–325.
11. L. Perioli, V. Ambrogi, S. Giovagnoli, M. Ricci, P. Blasi and C. Rossi, Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen, AAPS PharmSciTech.8 (2007) E20-E27; DOI: 10.1208/pt0803054.
12. H. Okamoto, H. Taguchi, K. Iida and K. Danjo, Development of polymer film dosage forms of lidocaine for buccal administration: I. Penetration rate and release rate, J. Control. Release77 (2001) 253–260; DOI: 10.1016/s0168-3659(01)00509-001.
13. Y. Sudhakar, K. Kuotsu and A. Bandyopadhyay, Buccal bioadhesive drug delivery—a promising option for orally less efficient drugs, J. Control. Release114 (2006) 15–40; 10.1016/j.jconrel.2006.04.012.
14. V. F. Patel, F. Liu and M. B. Brown, Advances in oral transmucosal drug delivery, J. Control. Release153 (2011) 106–116; DOI: 10.1016/j.jconrel.2011.01.027.
15. A. Bernkop-Schnürch and S. Steininger, Synthesis and characterisation of mucoadhesive thiolated polymers, Int. J. Pharm.194 (2000) 239–247; 10.1016/s0378-5173(99)00387-799.
16. I. Knight, The development and applications of sucralose, a new high-intensity sweetener, Can. J. Physiol. Pharmacol.72 (1994) 435–439; DOI: 10.1139/y94-063.
17. L. Allen, Featured excipient: capsule and tablet diluents, Int. J. Pharm. Compd.4 (2000) 306–312.
18. V. M. Patel, B. G. Prajapati, H. V. Patel and K. M. Patel, Mucoadhesive bilayer tablets of propranolol hydrochloride, AAPS PharmSciTech. 8 (2007) E203-E208; 10.1208/pt0803077.
19. L. Perioli, V. Ambrogi, D. Rubini, S. Giovagnoli, M. Ricci, P. Blasi and C. Rossi, Novel mucoadhesive buccal formulation containing metronidazole for the treatment of periodontal disease, J. Control. Release95 (2004) 521–533; DOI: 10.1016/j.jconrel.2003.12.018.
20. S. Mohammadi-Samani, R. Bahri-Najafi and G. Yousefi, Formulation and in vitro evaluation of prednisolone buccoadhesive tablets, Farmaco60 (2005) 339–344; DOI: 10.1016/j.farmac.2005.01.009.
21. S. Edavalath and B. Rao, Design, development and optimization of buccal bioadhesive tablets of diclofenac sodium for the treatment of odontalgia, Ars Pharm.52 (2011) 5–13.
22. M. S. Pendekal Ars Pharm P. K. Tegginamat, Formulation and evaluation of a bioadhesive patch for buccal delivery of tizanidine, Acta Pharm. Sin. B2 (2012) 318–324; DOI: 10.1016/j.apsb.2011.12.012.
23. N. Shah, G. Zhang, V. Apelian, F. Zeng, M. H. Infeld and A. W. Malick, Prediction of drug release from hydroxypropyl methylcellulose (HPMC) matrices: effect of polymer concentration, Pharm. Res.10 (1993) 1693–1695; DOI: 10.1023/a:1018901509855.
24. J. Malakar, A. K. Nayak and S. Goswami, Use of response surface methodology in the formulation and optimization of bisoprolol fumarate matrix tablets for sustained drug release, ISRN Pharmaceutics 2012 (2012), article ID 730624; DOI: 10.5402/2012/730624.
25. S. Dash, P. N. Murthy, L. Nath and P. Chowdhury, Kinetic modeling on drug release from controlled drug delivery systems, Acta Pol. Pharm.67 (2010) 217–223; DOI: 10.1080/10717540490265379.
26. D. Jones, Pharmaceutical Applications of Polymers for Drug Delivery, Smithers Rapra Publishing, U.K. 2004. pp. 31–35.
27. J. Parojčić, Z. Ðurić, M. Jovanović and S. Ibrić, An investigation into the factors influencing drug release from hydrophilic matrix tablets based on novel carbomer polymers, Drug Deliv.11 (2004) 59–65.
28. X. Huang and C. S. Brazel, On the importance and mechanisms of burst release in matrix-controlled drug delivery systems, J. Control. Release73 (2001) 121–136; DOI: 10.1016/s0168-3659(01)00248-601.