Evaluation of the presence of polymorphic forms and influence on the dissolution profile of Tenoxicam in active pharmaceutical ingredient and formulations
DOI:
https://doi.org/10.22456/2527-2616.90005Keywords:
tenoxicam, polymorphism, crystalline structure, active pharmaceutical ingredients, pharmaceutical formulationsAbstract
Polymorphism is a relatively common phenomenon among pharmaceutical compounds, and one of the main aspects to be considered in the production and development of medications. The investigation of polymorphism associated with oxicams, a group belonging to the class of non-steroidal anti-inflammatory drugs (NSAIDs) has increased in recent years and, in the case of tenoxicam, the existence of four polymorphic forms is reported in the literature. The objective of this study was to characterize the presence of different polymorphic forms of tenoxicam in active pharmaceutical ingredient and oral pharmaceutical formulations, as well as to evaluate the influence on in vitro dissolution. The characterization of the three samples of pharmaceutical ingredient of tenoxicam from different suppliers by X-Ray Diffraction (XRD), Infrared (IR) and dissolution profile indicated the presence of a form III crystalline structure, without presenting significant differences between the in vitro dissolution profiles analyzed, and a Dissolution Efficiency (DE%) of 60.30%, 60.70% and 72.34%, respectively. When the four pharmaceutical specialties of tenoxicam were submitted to XRD analysis, they also presented form III crystalline structures. Despite this, the formulations presented different dissolution profiles and a DE% of 75.23%, 83.69%, 78.19% and 90.63%, respectively, without compromising their quality. However, often polymorphism affects physico-chemical properties of drugs, showing the importance of studying this phenomenon, by correlating the presence of crystalline structures to alterations in the quality of active ingredients and pharmaceutical products.Downloads
References
Cuffini SL, Pitaluga AJ, Tombari D. Polimorfismo em fármacos. In: Storpirtis S, Gonçalves JE, Chiann C, Gai MN. Biofarmacotécnica. Rio de Janeiro: Guanabara Koogan; 2011:21-30.
LU J, Rohani S. Polymorphism and crystallization of active pharmaceutical ingredients (APIs). Curr. Med. Chem. 2009;16:884-905. DOI: https://doi.org/10.2174/092986709787549299
Allen LVJ, Popovich NG, Ansel HC. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 9th ed. Baltimore: Lippincott Willians & Willians; 2011.
Singhal D, Curatolo W. Adv. Drug polymorphism and dosage form design: a practical perspective. Drug Delivery Rev 2004;56:335-347. DOI: https://doi.org/10.1016/j.addr.2003.10.008
Capucho HC, Mastroianni PC, Cuffini S. Farmacovigilância no Brasil: a relação entre polimorfismo de fármacos, efetividade e segurança dos medicamentos. Rev. Ciênc. Farm. Básica Apl. 2008;29:277-283.
Oliveira MA, Yoshida MI, Gomes ECL. Análise térmica aplicada a fármacos e formulações farmacêuticas na indústria farmacêutica. Quim. Nova 2011;34:1224-1230. DOI: https://doi.org/10.1590/S0100-40422011000700022
Morris KR, Griesser UJ, Eckhardt CJ, Stowel JG. Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes. Adv. Drug Deliver. Rev. 2001;48:91-114. DOI: https://doi.org/10.1016/S0169-409X(01)00100-4
Stephenson GA. Applications of X-Ray Powder Diffraction in the Pharmaceutical Industry. Rigaku J. 2005;22:2-15.
Florence AT, Attwood D. Physicochemical Principles of Pharmacy. 3th ed. London: Palgrave Macmillan; 1998. DOI: https://doi.org/10.1007/978-1-349-14416-7
Zhang J, Tan X, Gao J, Fan W, Gao Y, Qian S. Characterization of two polymorphs of lornoxicam. Journal of Pharmacy and Pharmacology. J. Pharm. Pharmacol. 2013;65:44-52. DOI: https://doi.org/10.1111/j.2042-7158.2012.01573.x
Cantera RG, Leza MG, Bachiller CM. Solid Phases of Tenoxicam. J. Pharm. Sci. 2002;91:2240-2251. DOI: https://doi.org/10.1002/jps.10207
BRITISH PHARMACOPOEIA COMMISSION. British Pharmacopoeia 2013. London: The Stationery Office, 2013.
Alladi S, Shastri NR. Semi solid matrix formulations of meloxicam and tenoxicam: an in vitro and in vivo evaluation. Arch. Pharmacal Res. [Online] 2014. Apr. Available from: http://link.springer.com/article/10.1007/ s12272-014-0396-3/fulltext.html. [last acess 10 Jan 2016].
Kim T, Kang E, Chun I, Gwak H. Pharmacokinetics of formulated tenoxicam transdermal delivery systems. J. Pharm. Pharmacol. 2008;60:135-138. DOI: https://doi.org/10.1211/jpp.60.1.0017
Yu L, Reutzel-Edens SM, Mitchell CA. Crystallization and polymorphism of conformationally flexible molecules: Problems, patterns, and strategies. Org. Process Res. Dev. 2000;4:396-402. DOI: https://doi.org/10.1021/op000028v
Schmidt AC, Schwarz I, Mereiter K. Polymorphism and Pseudopolymorphism of salicaine and salicaine hydrochloride crystal polymorphism of local anaesthetic drugs. J. Pharm. Sci. 2006;95:1097-1113. DOI: https://doi.org/10.1002/jps.20533
Patel JR, Carlton RA, Needham TE, Chichester CO, Vogt FG. Preparation, structural analysis, and properties of tenoxicam cocrystals. International Journal of Pharmaceutics. Int. J. Pharm. 2012;436:685-706. DOI: https://doi.org/10.1016/j.ijpharm.2012.07.034
Bolla G, Sanphui P, Nangia A. Solubility advantage of tenoxicam phenolic cocrystals compared to salts. Cryst. Growth Des. 2013;13:1988-2003. DOI: https://doi.org/10.1021/cg4000457
Lin SY. An overview of famotidine polimorphs: solidstate characteristics, termodynamics, polymorphic transformation and quality control. Pharm Res 2014;31:1619-1631. DOI: https://doi.org/10.1007/s11095-014-1323-5
Karabas I, Orkoula MG, Kontoyannis CG. Analysis and stability of polymorphs in tablets: the case of Risperidone. Talanta 2007;71:1382-1386. DOI: https://doi.org/10.1016/j.talanta.2006.07.009
Pavia D, Kriz G, Lampman G. Introduction to spectroscopy: A guide for students of organic chemistry. 3rd ed. Washington: Brooks/Cole Thomson Learning; 2001.
Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm. Technol. 1996;20:64-74.
Yuksel N, Kanik AE, Baykara T. Comparison of in vitro dissolution profiles by ANOVA based, model dependent and independent methods. Int. J. Pharm 2000;209:57-67. DOI: https://doi.org/10.1016/S0378-5173(00)00554-8
Gibaldi M. Biopharmaceutics and Clinical Pharmacokinetics. 4th ed. Philadelpia: Lea & Febiger, 1991.
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