Development and Evaluation of Orodispersible Tablets Containing Ketoprofen

Author(s): Laiane J. Oliveira, Andressa Veiga, Nayana C. F. Stofella, Aline Carolina Cunha, Maria da Graça T. Toledo, Itamar F. Andreazza, Fabio S. Murakami*

Journal Name: Current Drug Delivery

Volume 17 , Issue 4 , 2020

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Graphical Abstract:


Abstract:

Background: Orodispersible Tablets (ODTs) are an option to facilitate the intake of pharmaceutical solid dosage forms, which dissolve in the mouth within 30 seconds releasing the drug immediately with no need for water intake or chewing.

Objective: The main goal of our study is the technological development of lactose-free orodispersible tablets that contain ketoprofen.

Methods: We assessed different variables during the pharmaceutical development of ODTs: compression techniques conducted after a wet granulation process, aiming to optimize the flow properties of the formulation, and a suspension freeze-drying molded in blisters. We developed three formulations for each method, each containing one of the superdisintegrants: croscarmellose, crospovidone, or starch glycolate.

Results: During the production of ODTs, we performed quality control of the granulation process, since the production of pellets contributed to the enhancement of the disintegration time and content homogeneity. Quality control tests for ODTs produced by freeze-drying were also satisfactory, despite significant changes in the final physical aspect of these products when compared to that of ODTs produced by compression. In addition, the disintegration times of ODTs produced by freeze-drying were substantially higher. Furthermore, these tablets displayed greater friability and pose a challenge to the control of a standard individual weight.

Conclusion: Among the superdisintegrants, croscarmellose contributed most significantly to reduce the disintegration time and to dissolve KTP effectively in 20 minutes.

Keywords: Pharmaceutical dosage forms, dissolution efficiency, development of formulations, freeze-drying, granulation, direct compression.

[1]
Slavkova, M.; Breitkreutz, J. Orodispersible drug formulations for children and elderly. Eur. J. Pharm. Sci., 2015, 75, 2-9.
[http://dx.doi.org/10.1016/j.ejps.2015.02.015] [PMID: 25736528]
[2]
Petrovick, G.F.; Kleinebudde, P.; Breitkreutz, J. Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties. Eur. J. Pharm. Biopharm., 2018, 122, 137-145.
[http://dx.doi.org/10.1016/j.ejpb.2017.10.018] [PMID: 29106946]
[3]
FDA; Food and Drug Administration, guidance for industry: orally disintegrating tablets, 2008. [Accessed June 15, 2019]; Available at: . https://www.fda.gov/regulatory-information/search-fda-guidance-documents/orally-disintegrating-tablets
[4]
Arshad, A.K.; Sarfaraz, M.D.; Doddayya, H. Design and evaluation of aceclofenac fast dissolving tablets prepared by crystallo-co-agglomeration technique. Int. J. Pharma Sci., 2011, 3, 116-123.
[5]
Gholve, S.; Kaware, A.; Thonte, S.; Kaudewar, D.; Bhusnure, O. Orodispersible tablets: a systematic review. World J. Pharm. Res, 2018, 7(6), 152-165.
[6]
Pandey, P.; Dahiya, M. Oral disintegrating tablets: a review. Int. J. Pharma. Res. Rev., 2016, 5(1), 50-62.
[7]
Camarco, W.; Ray, D.; Druffner, A. Selecting superdisintegrants for orally disintegrating tablet formulations. Pharm. Technol., 2006, 5, 1-4.
[8]
Comoglu, T.; Inal, O.; Yaacoub, H.B. Formulation and in vitro evaluation of ketoprofen fast-dissolving tablets. Pharm. Dev. Technol., 2016, 21(8), 901-908.
[http://dx.doi.org/10.3109/10837450.2015.1022792] [PMID: 25798913]
[9]
Aulton, M.E.; Taylor, K.M.G. Aulton delineamento de formas farmacêuticas, 4th ed.; Elsevier: Rio de Janeiro, . 2016, pp. 25.
[10]
Walsh, J.; Cram, A.; Woertz, K.; Breitkreutz, J.; Winzenburg, G.; Turner, R.; Tuleu, C. European Formulation Initiative. Playing hide and seek with poorly tasting paediatric medicines: do not forget the excipients. Adv. Drug Deliv. Rev., 2014, 73, 14-33.
[http://dx.doi.org/10.1016/j.addr.2014.02.012] [PMID: 24614069]
[11]
FDA; Food and Drug Administration analgesic development for pediatric patients, 2016.[Accessed February 01, 2020]; Available at: . https://www.fda.gov/media/96805/download
[12]
Porażka, J.; Karbownik, A.; Murawa, D.; Spychała, A.; Firlej, M.; Grabowski, T.; Murawa, P.; Grześkowiak, E.; Szałek, E. The pharmacokinetics of oral ketoprofen in patients after gastric resection. Pharmacol. Rep., 2017, 69(2), 296-299.
[http://dx.doi.org/10.1016/j.pharep.2016.11.010] [PMID: 28178590]
[13]
Shohin, I.E.; Kulinich, J.I.; Ramenskaya, G.V.; Abrahamsson, B.; Kopp, S.; Langguth, P.; Polli, J.E.; Shah, V.P.; Groot, D.W.; Barends, D.M.; Dressman, J.B. Biowaiver monographs for immediate-release solid oral dosage forms: ketoprofen. J. Pharm. Sci., 2012, 101(10), 3593-3603.
[http://dx.doi.org/10.1002/jps.23233] [PMID: 22786667]
[14]
Morais, M.B.; Fagundes, U.F. Alergia alimentar.Nutrição e dietética em clínica pediátrica; Lopez, F.A; Brasil, A.L.D., Ed.; Atheneu: São Paulo, 2003, pp. 210-219.
[15]
Rangel, A.H.N.; Sales, D.C.; Urbano, S.A.; Galvão Júnior, J.G.B.; Andrade Neto, J.C.; Macêdo, C.S. Lactose intolerance and cow’s milk protein allergy. Food Sci. Technol., 2016, 36(2), 179-187.http://dx.doi.org/http://dx.doi.org/10.1590/1678-457X.0019
[http://dx.doi.org/10.1590/1678-457X.0019]
[16]
Suchy, F.J.; Brannon, P.M.; Carpenter, T.O.; Fernandez, J.R.; Gilsanz, V.; Gould, J.B.; Hall, K.; Hui, S.L.; Lupton, J.; Mennella, J.; Miller, N.J.; Osganian, S.K.; Sellmeyer, D.E.; Wolf, M.A. NIH consensus development conference statement: Lactose intolerance and health. NIH Consens. State Sci. Statements, 2010, 27(2), 1-27.
[PMID: 20186234]
[17]
Santos, G.J.; Rocha, R.; Santana, G.O. Lactose intolerance: what is a correct management? Rev. Assoc. Med. Bras. (1992), 2019, 65(2), 270-275.
[http://dx.doi.org/10.1590/1806-9282.65.2.270]
[18]
Oliveira, L.J.; Stofella, N.C.F.; Veiga, A.; Féderle, S.; Toledo, M.G.T.; Bernardi, L.S.; Oliveira, P.R.; Filho, M.A.S.C.; Andreazza, I.F.; Murakami, F.S. Physical-chemical characterization studies of ketoprofen for orodispersible tablets. J. Therm. Anal. Calorim., 2018, 133(3), 1521-1533.
[http://dx.doi.org/10.1007/s10973-018-7195-x]
[19]
Allen, J.R.; Popovich, N.G.; Ansel, H.C. Formas farmacêuticas e sistemas de liberação de fármacos, 9th ed; Artmed: Porto Alegre, 2013.
[20]
USP - United States pharmacopeia and the national formulary (USP 41 - NF 36); The United States Pharmacopeia Convention: Rockville, MD, 2018.
[21]
Carr, R.L. Evaluating flow properties of solids. Chem. Eng., 1965, 72, 163-168.
[22]
Hausner, H.H. Friction conditions in a mass of metal powder. Int. J. Metall, 1967, 3, 7-13.
[23]
Agência Nacional de Vigilância Sanitária (ANVISA). Farmacopeia Brasileira, 5th ed; Brasília, 2010.
[24]
Chandrasekhar, R.; Hassan, Z.; Alhusban, F.; Smith, A.M.; Mohammed, A.R. The role of formulation excipients in the development of lyophilised fast-disintegrating tablets. Eur. J. Pharm. Biopharm., 2009, 72(1), 119-129.
[http://dx.doi.org/10.1016/j.ejpb.2008.11.011] [PMID: 19073253]
[25]
ICH Harmonized tripartite guideline. Validation of analytical procedures: text and methodology Q2 (R1),; 2005.[Accessed April 15, 2019]; Available at: . https://www.ich.org/fileadmin/Public_Web_Site/ ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf
[26]
Agência Nacional de Vigilância Sanitária (ANVISA). Resolução RDC nº 31, de 11 de agosto de;; Brasil , 2010.
[27]
Khan, K.A.; Rhodes, C.T. The concept of dissolution efficiency. J. Pharm. Pharmacol., 1975, 27(1), 48-49.
[http://dx.doi.org/10.1111/j.2042-7158.1975.tb09378.x] [PMID: 235616]
[28]
Ofoefule, S.I.; Udeogaranya, P.O.; Okonta, J.M. Prediction of in vivo bioavailability of six brands of ciprofloxacin film coated tablets using the concept dissolution efficiency (DE). Boll. Chim. Farm., 2001, 140(3), 187-191.
[PMID: 11486612]
[29]
Serra, C.H.R.; Storpirtis, S. Comparação de perfis de dissolução da cefalexina através de estudos de cinética e eficiência de dissolução (ED%). Braz. J. Pharm. Sci., 2007, 43(1), 79-88.
[30]
EMA, European Medicines Agency, Science Medicines Health Background review for sodium laurilsulfate used as an excipient,; 2015 [Accessed May 15, 2019]; Available at:. https://www.ema.europa.eu/ documents/report/background-review-sodium-laurilsulfate-used-excipient-context-revision-guideline-excipients-label_en.pdf
[31]
Prista, L.N.; Alves, A.C.; Morgado, R.M.R. Tecnologia Farmacêutica, 6th ed; Fundação Calouste Gulbenkian: Lisboa, 2003.
[32]
Propst, C.W. Granulation Characterization.Handbook of pharmaceutical granulation technology, 3rd ed; Parikh, D.M., Ed.; Informa Healthcare: New York, 2010, pp. 469-484.
[33]
Lamolha, M.A.; Serra, C.H.R. Avaliação das propriedades de fluxo dos granulados e dissolução de comprimidos de hidroclorotiazida 50 mg obtidos por granulação úmida. Braz. J. Pharm. Sci., 2007, 43(3), 436-446.
[34]
Shukla, D.; Chakraborty, S.; Singh, S.; Mishra, B. Mouth dissolving tablets I: an overview of formulation technology. Sci. Pharm., 2009, 77, 309-326.
[http://dx.doi.org/10.3797/scipharm.0811-09-01]
[35]
Manadas, R.; Pina, M.E.; Veiga, F. A dissolução in vitro na previsão da absorção de fármacos em formas farmacêuticas de liberação modificada. Rev. Bras. Cienc. Farm, 2002, 38(4), 375-399.
[http://dx.doi.org/10.1590/S1516-93322002000400002]


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Article Details

VOLUME: 17
ISSUE: 4
Year: 2020
Page: [348 - 360]
Pages: 13
DOI: 10.2174/1567201817666200317122807
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