FORMULATION OF ORALLY DISINTEGRATING TABLETS OF CINNARIZINE BY USING DIRECT COMPRESSION METHOD
Keywords:Orally disintegrating tablets, Super disintegrants, Cinnarizine, Direct compression
Objective: The aim of this work was to formulate and evaluate orally disintegrating tablets of cinnarizine that were prepared by direct compression method using different types of diluents and super disintegrants. The rationale behind this work was to accelerate the disintegration of the tablet to provide rapid dissolution, quick action and enhanced bioavailability of the drug.
Methods: The tablets were prepared by direct compression method using different types of diluents as mannitol, microcrystalline cellulose (MCC), and lactose. Different super disintegrants were used such as crospovidone (CP), sodium starch glycolate (SSG) and Kyron T-314; Kyron T-314 was used in different concentrations of 5%, 6%, 7%, and 8%. The prepared formulae (F1-F9c) were subjected to flowability studies and post-compression evaluation studies. The optimized formula was selected depending on the time of disintegration and dissolution; then it was subjected to drug-excipient compatibility study and stability study.
Results: Flowability results were ranging from excellent, excellent to good, and good to fair according to the type of the diluent used. All of the prepared tablets showed acceptable hardness, friability, drug content, and disintegration. A rapid disintegration of 11.66Â±2.25 s with the highest percentage 2 min-drug release of 74.55Â±3.01% was obtained by using the diluent lactose and the super disintegrant Kyron T-314 (8%) in the formula F9c. The infrared spectroscopic studies of the formula F9c showed no drug-excipient interaction. In addition, the stability study indicated that the optimized formula is a stable formula.
Conclusion: Formula F9c of a rapidly disintegrating tablet was easy to be manufactured, and the results showed that this formula had a rapid disintegration, high dissolution profile, no noticeable chemical incompatibility and it was stable upon storage.
Gryczke A, Schminke S, Maniruzzaman M, Beck J, Douroumis D. Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion. Colloids Surf B 2011;86:275â€“84.
Abdelbary G, Prinderre P, Eouani C, Joachim J, Reynier JP, Piccerelle P. The preparation of orally disintegrating tablets using a hydrophilic waxy binder. Int J Pharm 2004;278:423â€“33.
Ph. Eur. European Pharmacopoeia. 9th ed. Council of Europe, Strasbourg; 2017.
Prajapati BG, Patel SN. Formulation, evaluation, and optimization of the orally disintegrating tablet of cinnarizine. E-J Sci Technol 2010;1:9â€“21.
Bhowmik D, Chiranjib B, Chandira RM. Fast dissolving tablet: an overview. J Chem Pharm Res 2009;1:163â€“77.
Singh S, Shah D. Development and characterization of mouth dissolving tablet of zolmitriptan. Asian Pacific J Trop Dis 2012;2(Suppl 1):S457â€“64.
Abdelbary A, Elshafeey AH, Zidan G. Comparative effects of different cellulosic-based directly compressed orodispersable tablets on the oral bioavailability of famotidine. Carbohydr Polym 2009;77:799â€“806.
Tripathi K. Essentials of medical pharmacology; 2013. Available from: http://www.jaypeedigital.com/book details. aspx?id=9789350259375andsr=1. [Last accessed on 05 Aug 2018].
Martindale W. Martindale the extra pharmacopoeia hardcover. 31st ed. Rittenhouse Book Distributors; 1996.
BergstrÃ¶m CAS, Fagerberg J, Tsinman O, Tsinman K, Avdeef A. Dissolution rate and apparent solubility of poorly soluble compounds in biorelevant fluids. Mol Pharm 2010;5:1801.
USP 33-NF 28. United States Pharmacopeial Convention. Rockville MD, USA; 2010.
Traina K, Cloots R, Bontempi S, Lumay G, Vandewalle N, Boschini F. Flow abilities of powders and granular materials evidenced from dynamical tap density measurement. Powder Technol 2013;235:842â€“52.
Shivakumar HN, Kumar MR. Formulation of fast dissolving tablets of doxazocin mesylate drug by direct compression method. Int J Appl Pharm 2017;9:22â€“8.
Nagar P, Singh K, Chauhan I, Verma M, Yasir M, Khan A, et al. Orally disintegrating tablets: formulation, preparation techniques, and evaluation. J Appl Pharm Sci 2011;1:35â€“45.
Patel BP, Patel JK, Rajput GC, Thakor RS. Formulation and evaluation of mouth dissolving tablets of cinnarizine. Indian J Pharm Sci 2010;72:522â€“5.
Santosh Kumar R, Naga Satya Yagnesh T, Goutham Kumar Gitam V. Optimisation of ibuprofen fast dissolving tablets employing starch xanthate using 23 factorial design. Int J Appl Pharm 2017;9:51â€“9.
Tambawala TS, Shah PJ, Shah SA. Orally disintegrating tablets of cinnarizine and domperidone: a new arsenal for the management of motion sickness. J Pharm Sci Tech Mgmt 2015;1:81â€“97.
Shaikh RH, Jamadar MJ, Patil AD, Tamboli SM. Formulation and in vitro evaluation of antiemetic orodispersible combination tablets of domperidone and cinnarizine by using various superdisintegrants. Pharmatutor 2015;3:49â€“59.
Bajaj S, Singla D, Sakhuja N. Stability testing of pharmaceutical products. J Appl Pharm Sci 2012;2:129â€“38.
Rowe RC. editor. Handbook of pharmaceutical excipients. 6. ed. London: APhA, (PhP) Pharmaceutical Press; 2009.
Thoorens G, Krier F, Leclercq B, Carlin B, Evrard B. Microcrystalline cellulose, a direct compression binder in quality by design environment-a review. Int J Pharm 2014;473:64â€“72.
Jivraj M, Martini LG, Thomson CM, Thomson CM. An overview of the different excipients useful for the direct compression of tablets. PSTT 2000;3:58â€“63.
Yassin S, Goodwin DJ, Anderson A, Sibik J, Wilson DI, Gladden LF, et al. The disintegration process in microcrystalline cellulose-based tablets, part 1: influence of temperature, porosity, and superdisintegrants. J Pharm Sci 2015;104:3440â€“50.
Ferrari F, Bertoni M, Bonferoni MC, Rossi S, Caramella C, NystrÃ¶m C. Investigation on bonding and disintegration properties of pharmaceutical materials. Int J Pharm 1996;136:71â€“9.
Battu SK, Repka MA, Majumdar S, Madhusudan RY. Formulation and evaluation of rapidly disintegrating fenoverine tablets: effect of superdisintegrants. Drug Dev Ind Pharm 2007;33:1225â€“32.
Bele MH, Derle DV. Mechanism of disintegrant action of polacrilin potassium: swelling or wicking? Acta Pharm Sin B 2012;2:70â€“6.
Setty CM, Prasad DVK, Gupta VRM, Sa B. Development of fast dispersible aceclofenac tablets: effect of the functionality of superdisintegrants. Indian J Pharm Sci 2008;70:180â€“5.
Swatantra S, Shweta S, Anil S. Comparative study on the effect of various superdisintegrants in the formulation of ibuprofen fast dissolving tablets. Int J Pharma Res Rev 2014;3:26â€“33.
Lakshmi PK, Narendra Y, Rewanthwar SL, Neeharika V. Comperative evaluation of natural and synthetic superdisintegrants in the formulation of fast dissolving tablets. Turk J Pharm Sci 2013;10:351â€“66.
Gohel MC. A review of co-processed directly compressible excipient. J Pharm Pharm Sci 2005;8:76â€“93.
BP. British Pharmacopoeia. London, Stationary office; 2017.
Abd-El Bary A, Louis D, Sayed S. Olmesartan medoxomil surface solid dispersion-based orodispersible tablets: formulation and in vitro characterization. J Drug Delivery Sci Technol 2014;24:665â€“72.
Gattu J, Lakshmi P. Comparative evaluation of natural and synthetic superdisintegrants with newer superdisintegrant kyron T-314. Acta Pharm Sci 2011;53:35â€“44.
Listiohadi Y, Hourigan JA, Sleigh RW, Steele RJ. Moisture sorption, compressibility and caking of lactose polymorphs. Int J Pharm 2008;359:123â€“34.