METHOTREXATE FAST DISINTEGRATING TABLET AS A DOSAGE FORM FOR DYSPHAGIA PATIENTS
Objective: The objective of the present study was to develop, optimize and evaluate fast disintegrating tablet (FDT) of methotrexate (MTX) as a dosage form for dysphagia patients with a view to enhance patient compliance and safety.
Methods: FDT was prepared by direct compression technique and effect of incorporating major excipients such as Croscarmellose Sodium (CCS), Crospovidone (CP), Sodium Starch Glycolate (SSG), neusilin and magnesium stearate on various parameters were evaluated. The blends prepared were evaluated for pre and post compression evaluations. The optimized FDT was assessed for various studies such as FT-IR, Differential Scanning Calorimeter (DSC), X-Ray Diffraction (XRD), in vitro disintegration, dissolution, in vivo pharmacokinetic and stability studies.
Results: The optimized blend mixture had good flow and compressible property; hence tablets produced were of uniform weight with acceptable weight variation. The drug content assessed by HPLC was within limits indicating drug had uniformly distributed in the tablets. Tablet produced can withstand abrasion during handling, packaging and shipment as tablet had optimum hardness and least friability. There was no drug-excipient incompatibility as confirmed by FT-IR and DSC studies. Change in crystalline nature of the drug after tableting was confirmed by XRD studies. FDT prepared using CP showed quick disintegration with excellent dissolution rate profile and exhibited satisfactory stability at normal temperature. In vivo studies of FDTs (test) compared with drug solution (control) showed no statistically significant difference in pharmacokinetic parameters.
Conclusion: The study indicated that MTX FDT disintegrates rapidly in seconds and hence is a promising dosage form for dysphagia patients.
2. Paterson WG. Dysphagia in the elderly. Can Fam Physician 1996;42:925-32.
3. Jackson LD, Little J, Kung E, William EM, Siemiatkowska K, Plowman S. Safe medication swallowing in dysphagia: A collaborative improvement project. Healthcare Quart 2008;11:110-16.
4. Cancer. Available From: http: //training. seer. cancer. gov/disease/cancer/ [Last Accessed on 2012 Apr 12].
5. Marimuthu P. Projection of cancer incidence in five cities and cancer mortality in India. Ind J Cancer 2008;45:4-7.
6. Goel P, Singh K, Kaur A, Verma M. Oral healthcare for elderly: Identifying the needs and feasible strategies for service provision. Ind J Dent Res 2006;17:11-21.
7. Ridge JA, Glisson BS, Lango MN, Feigenberg S. Head and Neck Tumors. Available From: http: //www. cancernetwork. com/cancer-management/head-and-neck/article/10165/1802498# [Last accessed on 2012 June 20].
8. Head and neck cancer in India. Available From: http: //www. veedaoncology. com/PDF-Document/Head-Neck%20Cancer%20In%20India. pdf [Last accessed on 2012 March 20].
9. Methotrexate. Available From: http: //drugsarea. com/Dets-Drugs/Methotrexatepd. html [Last accessed on 2012 March 20].
10. Methotrexate drug information provided by Lexi-Comp. Available From: http: //www. merckmanuals. com/professional/lexicomp/methotrexate. html [Last accessed on 2012 March 21].
11. Abed KK, Hussein AA, Ghareeb MM, Abdulrasool AA. Formulation and optimization of orodispersible tablets of diazepam. AAPS Pharma Sci Tech 2010;11:356-61.
12. Fini A, Bergamante V, Ceschel GC, Ronchi C, Carlos AFM. Fast dispersible/slow releasing ibuprofen tablets. Eur J Pharm and Biopharm 2008;69:335â€“41.
13. Kulkarni PK, Dixit AS, Singh BS. Evaluation of bacterial cellulose produced from Acetobacter xylinum as pharmaceutical excipient. Amer J Drug Disc Dev 2012;2:72-86.
14. USP method for HPLC. Available From: http: //www. chem. agilent. com/Library/applications/(PH23)5988-6394EN. pdf [Last accessed on 2012 March 21].
15. USP 35-NF 30. US Pharmacopeia & National Formulary. The United States Pharmacopeial Convention; 2012.
16. Khalid KA, Hussein AA, Ghareeb MM, Abdulrasool AA. Formulation and optimization of orodispersible tablets of diazepam. AAPS Pharm Sci Tech 2010;11:356-61.
17. Arya A, Chandra A. Fast drug delivery systems. A Review: Der Pharmacia Lettre 2010;2:350-61.
18. Shukla D, Chakraborty S, Singh S, Mishra B. Mouth Dissolving Tablets II: An overview of evaluation techniques. Sci Pharm 2009;77:327â€“41.
19. Nishimura M, Matsuura K, Tsukioka K, Yamashita H, Inagaki N, Sugiyama T, et al. In vitro and in vivo characteristics of prochlorperazine oral disintegrating film. Int J Pharm 2009;368:98-102.
20. Wang F, Jiang Xinguoa, Lu Wei. Profiles of methotrexate in blood and CSF following intranasal and intravenous administration to rats. Int J Pharm 2003;263:1â€“7.
21. Jeong SH, Takaishi Y, Fu Yourong, Park Kinam. Materials properties for making fast dissolving tablets by a compression method. J Mater Chem 2008;18:3527-35.
22. Rowe RC, Sheskey PJ, Quinn ME: Handbook of pharmaceutical excipients, 5th ed. London: Pharmaceutical Press; 2009.
23. Setty CM, Prasad DVK, Gupta VRM, Sa B. Development of fast dispersible aceclofenac tablets: effect of functionality of superdisintegrants. Ind J Pharm Sci 2008;70:180-5.
24. Durig T, Fassihi R. Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experimental extended release formulation. J Pharm Sci 1997;86:1092â€“98.
25. Shihora H, Panda S. Superdisintegrants, Utility in Dosage Forms: A Quick Review. J Pharm Sci Bio-sci Res 2011;13:148-53.
26. Neusilin US2. The extraordinary excipient for solid dosage forms. Technical newsletter/Nov 2007. Available From: http: //www. fujichemical. co. jp/english/newsletter/ newsletter _pharma_0711. html [Last accessed on 201 Dec 11].
27. Durig T, Fassihi R. Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experimental extended release formulation. J Pharm Sci 1997;86:1092â€“98.
28. Sucralose. Available From: http: //en. wikipedia. org/wiki/Sucralose [Last accessed on 2011 Dec 9].
29. Chandak AR, Verma PRP. Design and development of hydroxypropyl methylcellulose (HPMC) based polymeric films of methotrexate: physicochemical and pharmacokinetic evaluations. Yakugaku zasshi 2008;128:1057-66.
30. Mohanachandran PS, Sindhumol PG, Kiran TS. Superdisintegrants: An overview. Int J Pharm Sci Rev Res 2011;6:105-9.
31. US. Food and drug administration, Guidance for industry orally disintegrating tablets. Available on: http: //www. fda. gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070578. pdf [Last accessed on 2012 Feb 15].
32. Fu Y, Jeong SH, Park K. Preparation of fast dissolving tablets based on mannose. ACS Symp Ser 2006;924:340â€“51.
33. Velpandian T, Mathur R, Agarwal NK, Arora B, Kumar L, Gupta SK. Development and validation of a simple liquid chromatographic method with ultraviolet detection for the determination of imatinib in biological samples. J Chromatogr B 2004;804:431-34.
34. Dixit AS, Kulkarni PK. Fast disintegrating films containing anastrozole as a dosage form for dysphagia patients. Arch Pharm Res 2012;35:2171-82.