Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2015.08.016
Brazilian Journal of Anesthesiology
Scientific Article

Mucoadhesive buccal films of tramadol for effective pain management

Filmes bucais mucoadesivos de tramadol para o controle eficaz da dor

Xiao-Qin Li; Zhao-Ming Ye; Jian-Bing Wang; Cai-Rong Fan; Ai-Wu Pan; Cong Li; Ren-Bing Zhang

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Abstract

Abstract Background and objectives: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is used in the management of chronic pain and is recommended as first line drug in the treatment of postoperative or orthopedic injury induced acute pain. The present work is designed to prepare and evaluate mucoadhesive buccal film of tramadol hydrochloride as a novel form of prolonged analgesia for patients with orthopedic injuries. Methods: Buccal films of tramadol hydrochloride were prepared by solvent casting method. The prepared films were evaluated for the various evaluation parameters like thickness, surface pH, weight uniformity, content uniformity, folding endurance, swelling index, in vitro drug release study, in vitro test for mucoadhesion and in vivo studies (primary mucosal irritancy test and analgesic activity). Results: All the formulations exhibited good results for physicochemical characterizations. In in vitro drug release study the films exhibited controlled release more than 12 hours. The formulation BFT2 (containing chitosan and PVP K-90) showed no irritant effect on buccal mucosa and elicit the significant in vivo analgesic activity with 57.14% analgesia against that of standard (61.04%). It was concluded that the mucoadhesive films of tramadol hydrochloride can be effectively used to alleviate the severe pain of orthopedic injuries with prompt onset and prolonged action.

Keywords

Mucoadhesion, Buccal film, Tramadol, Analgesia, Swelling, Orthopedic injury

Resumo

Resumo Justificativa e objetivos: O cloridrato de tramadol é um analgésico opioide de ação central que se liga a receptores opioides específicos. É usado no tratamento de dor crônica e recomendado como fármaco de primeira linha para o tratamento no pós-operatório ou em dor aguda induzida por lesão ortopédica. O presente estudo visa a preparar e avaliar o filme bucal mucoadesivo de cloridrato de tramadol como uma nova forma de analgesia prolongada para pacientes com lesões ortopédicas. Método: Filmes bucais de cloridrato de tramadol foram preparados pelo método de evaporação de solvente. Os filmes preparados foram avaliados para os vários parâmetros de avaliação, como espessura, pH da superfície, uniformidade do peso, uniformidade do conteúdo, resistência a dobras, índice de intumescimento, estudo de liberação da droga in vitro, teste in vitro para mucoadesão e estudos in vivo (teste de irritação da mucosa primária e atividade analgésica). Resultados: Todas as formulações apresentaram bons resultados para caracterizações físico-químicas. Em estudo de libertação de droga in vitro, os filmes exibiram liberação controlada por mais de 12 horas. A formulação de BFT2 (com quitosana e PVP K-90) não mostrou efeito irritante sobre a mucosa bucal e provocou uma atividade analgésica significativa in vivo com 57,14% de analgesia versus a do padrão (61,04%). Concluiu-se que os filmes mucoadesivos de cloridrato de tramadol podem ser usados eficazmente para aliviar a dor intensa de lesões ortopédicas com início rápido e ação prolongada.

Palavras-chave

Mucoadesão, Filme bucal, Tramadol, Analgesia, Edema, Lesão ortopédica

References

Semalty A, Bhojwani M, Bhatt GK, Gupta GD, Shrivastav AK. Design and evaluation of mucoadhesive buccal films of diltiazem hydrochloride. Indian J Pharm Sci. 2005;67:548-52.

Lu Z, Chen W, Hamman J. Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release. Curr Drug Deliv. 2007;4:257-63.

Verma S, Kaul M, Rawat A, Saini S. An overview on buccal drug delivery system. Ind J Pharm Sci Res. 2011;2:1303-21.

Boddupalli BM, Mohammad ZNK, Nath RA, Banji D. Mucoadhesive drug delivery system an overview. J Adv Pharm Tech Res. 2010;1:381-7.

Giannoidis P, Furlong A, Macdonald D. Non-union of the femoral diaphysis: the influence of reaming and non-steroidal anti-inflammatory drugs (NSAIDs). J Bone Joint Surg. 2000;82:655-8.

Kalinkova GN. Studies of beneficial interactions between active medicaments and excipients in pharmaceutical formulations. Int J Pharm. 1999;187:1-15.

Grant PS. Analgesia delivery in the ED. Am J Emerg Med. 2000;24:806-9.

Semalty A, Semalty M, Nautiyal U. Formulation and evaluation of mucoadhesive buccal films of enalapril maleate. Indian J Pharm Sci. 2010;72:576-81.

Semalty M, Semalty A, Kumar G. Formulation and characterization of mucoadhesive buccal films of glipizide. Indian J Pharm Sci. 2008;70:43-8.

Ramarao P, Diwan PV. Formulation and in vitro evaluation of polymeric films of diltiazem hydrochloride and indomethacin for transdermal administration. Drug Dev Ind Pharm. 1998;24:327-36.

Woolfson DD, McCafferty F, Moss GP. Development and characterization of a moisture-activated bioadhesive drug delivery system for a percutaneous local anesthesia. Int J Pharm. 1998;169:83-94.

Biswajit B, Kevin G, Thimmasetty J. Formulation and evaluation of pimozide buccal mucoadhesive films. Int J Pharm Sci Nanotechnol. 2010;2:739-48.

Noha AN, Nabila AB, Fatma AI, Lobna MM. Design and characterization of mucoadhesive buccal films containing cetylpyrinium chloride. Acta Pharm. 2003;53:199-212.

Shidhaye SS, Saindane NS, Sutar S, Kadam V. Mucoadhesive bilayered patches for administration of sumatriptan succinate. AAPS PharmSciTech. 2008;9:909-16.

Guyot M, Fawaz F. Design and in vitro evaluation of adhesive matrix for transdermal delivery of propranolol. Int J Pharm. 2000;204:171-82.

Patel RS, Poddar SS. Development and characterization of mucoadhesive buccal films of Salbutamol sulphate. Curr Drug Deliv. 2009;6:140-4.

Dhankar V, Garg G, Dhamija K, Awasthi R. Preparation, characterization and evaluation of ranitidine hydrochloride-loaded mucoadhesive microspheres. Polim Med. 2014;44:75-81.

Tojo K, Hikima T. Bioequivalence of marketed transdermal delivery systems for tulobuterol. Biol Pharm Bull. 2007;30:1576-9.

Deshmane SV, Channawar MA, Chandewar MA, Joshi UM, Biyani KR. Chitosan based sustained release mucoadhesive buccal films containing verapamil HCl. Int J Pharm Pharma Sci. 2009;1:216-29.

Patel JK, Chavda JR. Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P mucoadhesive microspheres for anti-Helicobacter pylori therapy. J Microencapsul. 2009;26:365-76.

Patel JK, Patel RP, Amin AF, Patel MM. Formulation and evaluation of mucoadhesive glipizide microspheres. AAPS PharmSciTech. 2005;20:E49-55.

Shojaei AH, Chang RK, Guo X, Burnside BA, Couch RA. Systemic drug delivery via the buccal mucosa route. Pharm Technol. 2001:70-81.

Agarwal S, Aggarwal S. Mucoadhesive polymeric platform for drug delivery; a comprehensive review. Curr Drug Deliv. 2015;12:139-56.

Morales JO, Huang S, Williams 3rd RO, McConville JT. Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery. Coll Surf B Biointerf. 2014;122:38-45.

Perioli L, Ambrogi V, Angelici F. Development of mucoadhesive patches for buccal administration of ibuprofen. J Control Rel. 2004;14:73-82.

Cid YP, Pedrazzi V, de Sousa VP, Pierre MB. In vitro characterization of chitosan gels for buccal delivery of celecoxib: influence of a penetration enhancer. AAPS PharmSciTech. 2012;13:101-11.

Kamel R, Mahmoud A, El-Feky G. Double-phase hydrogel for buccal delivery of tramadol. Drug Dev Ind Pharm. 2012;38:468-83.

Messina J, Darwish M, Fine PG. Fentanyl buccal tablet. Drugs Today (Barc). 2008;44:41-54.

Mercadante S. Oral trasmucosal fentanyl citrate for breakthrough pain treatment in cancer patients. Expert Opin Pharmacother. 2012;13:873-8.

Taylor DR. Single-dose fentanyl sublingual spray for breakthrough cancer pain. Clin Pharmacol. 2013;24:131-41.

Davies AI, Finn A, Tagarro I. Intra- and inter individual variabilities in the pharmacokinetics of fentanyl buccal soluble film in healthy subjects: a cross-study analysis. Clin Drug Investig. 2011;31:317-24.

Morales ME, Ruiz MA, López G, Gallardo V. Development of oral suspensions of microparticles of ethylcellulose with tramadol. Drug Dev Ind Pharm. 2010;36:885-92.

Barkin RL. Extended-release tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Am J Ther. 2008;15:157-66.

Belgamwar VS, Patel HS, Joshi AS, Agrawal A, Surana SJ, Tekade AR. Design and development of nasal mucoadhesive microspheres containing tramadol HCl for CNS targeting. Drug Deliv. 2011;18:353-60.

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