Abstract
The purpose of this work was to develop novel taste masked mouth-dissolving tablets of tramadol that overcomes principle drawback of such formulation which is inadequate mechanical strength. Tramadol is an opioid analgesic used for the treatment of moderate to severe pain. Mouth-dissolving tablets offer substantial advantages like rapid onset of action, beneficial for patients having difficulties in swallowing and in conditions where access to water is difficult. The crucial aspect in the formulation of mouth-dissolving tablets is to mask the bitter taste and to minimize the disintegration time while maintaining a good mechanical strength of the tablet. Mouth-dissolving tablets of tramadol are not yet reported in the literature because of its extreme bitter taste. In this work, the bitter taste of Tramadol HCl was masked by forming a complex with an ion exchange resin Tulsion335. The novel combination of a superdisintegrant and a binder that melts near the body temperature was used to formulate mechanically strong tablets that showed fast disintegration. A 32 full factorial design and statistical models were applied to optimize the effect of two factors, i.e., superdisintegrant (crospovidone) and a mouth-melting binder (Gelucire 39/01). It was observed that the responses, i.e., disintegration time and percent friability were affected by both the factors. The statistical models were validated and can be successfully used to prepare optimized taste masked mouth-dissolving tablets of Tramadol HCl with adequate mechanical strength and rapid disintegration.
Similar content being viewed by others
References
Grond S, Sablotzi A. Clinical pharmacology of tramadol. Clin Pharmacokinet 2004;43(13):879–923.
Bagul U et al. Manufacturing technologies for mouth dissolving tablets. www.pharmainfo.net, 2006; May 31.
Biradar S, Bhagavati S and Kuppasad. Fast dissolving drug delivery system: a brief overview. Internet J Pharmacol. 2006;4(2).
Chang R, Guo X, Burnside B, Couch R. Fast-dissolving tablets. Pharm Technol 2000;24(6):52–8.
Bogner R, Meghan F. Fast dissolving tablets. US Pharmacist 2005;27:03.
Sohi H, Sultana Y, Khar R. Taste masking technologies in oral pharmaceuticals: recent development and approaches. Drug Dev Ind Pharm 2004;30:429–48.
Borodkin S, Sundberg D. Polycarboxylic acid ion-exchange adsorbates for taste coverage in chewable tablets. J Pharm Sci 1971;50:1523.
Avari J, Bhalekar M. Cation exchange resins for taste masking and rapid dissolution of sparfloxacin. Indian Drugs 2004;41(1):19–23.
Pisal S, Zainnuddin R, Nalawade P, Mahadik K, Kadam S. Molecular properties of ciprofloxacin–indion 234 complexes. AAPS PharmSciTech 2004;5(4):e62.
Chaudhari P, Chaudhari S, Lanke S, Patel N. Formulation and in vitro evaluation of taste masked orodispersible dosage form of Levocetirizine dihydrochloride. Indian J Pharm Edu Res 2007;41(4):319–28.
Kalsi P. Spectroscopic identification of organic compounds, 5th ed. New Delhi: New Age International Publishers; 2002. p. 84–102.
Skoog D, Holler F, Nieman T. The principles of instrumental analysis, 5th ed. Singapore: Thomson Book/Cole; 1998. p. 805–8.
Bolton S. Pharmaceutical statistics, 2nd ed. New York: Marcel Decker; 1990. p. 532–34.
Singh B, Ahuja N. Response surface optimization of drug delivery system. In: Jain NK, editor. Progress in controlled and novel drug delivery systems, 1st ed. New Delhi: CBS Publishers and Distributors; 2004. p. 470–509.
Singh B, Ahuja N. Development of controlled release buccoadhesive hydrophilic matrices of diltiazem hydrochloride: optimization of bioadhesion, dissolution and diffusion parameters. Drug Dev Ind Pharm 2002;28:433–44.
Gohel M, Patel M, Agarwal R, Amin A, Dave R, Bariya N. Formulation design and optimization of mouth dissolving tablets of nimesulide using vacuum drying technique. AAPS PharmSciTech 2004;5(3):36.
Lachmann L, Liberman H, Kanig J. The theory and practice of industrial pharmacy, 3rd edn. Mumbai: Varghese; 1987. p. 296–300.
Indian Pharmacopoeia 1996, vol I. The controller of publications, New Delhi.
Morita Y, Tsushima Y, Termoz R, Ajioka J, Takayama K. Evaluation of disintegration time of rapidly disintegrating tablets via a novel method using a CCD camera. Chem Pharm Bull (Tokyo) 2002;50:1181–6.
Watanabe Y, Yamamoti Y, Fujii M, Kondoh M, Shibata Y. A novel method for predicting disintegration time in the mouth of rapid disintegrating tablet by compaction analysis using Tab All. Chem Pharm Bull (Tokyo) 2004;52:1394–5.
Narazki R, Harada T, Takami N, Koto Y, Ohwaki T. A new method for disintegration studies of rapid disintegrating tablets. Chem Pharm Bull (Tokyo) 2004;52:704–7.
Kuchekar B, Badhan A, Mahajan H. Mouth dissolving tablets of salbutamol sulphate: a novel drug delivery system. Indian Drugs 2004;41(10):592–8.
United States Pharmacopoeia 29-NF 24. The Official Compendia of Standards. Asian ed. Rockville, MD: United States Pharmacopoeial Convention Inc.; 2006. p. 2679–2681.
Khan S, Kataria P, Nakhat P, Yeole P. Taste masking of Ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets. AAPS PharmSciTech 2007;8(2):e46.
Acknowledgments
We are thankful to Lupin Labs, Pune, Gattefosse, France, ISP Corp., Hong Kong, Iatros Pharma, Pune, and Keva flavors, Mumbai for providing necessary materials as gift samples. We also express sincere thanks to Dr. K.G. Bothara, Principal, AISSMS College of Pharmacy, Pune for providing necessary facilities to carry out this research work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Madgulkar, A.R., Bhalekar, M.R. & Padalkar, R.R. Formulation Design and Optimization of Novel Taste Masked Mouth-Dissolving Tablets of Tramadol Having Adequate Mechanical Strength. AAPS PharmSciTech 10, 574–581 (2009). https://doi.org/10.1208/s12249-009-9237-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-009-9237-y