PREFORMULATION STUDIES OF TRANSDERMAL THERAPEUTIC SYSTEMS CONTAINING BETAHISTINE

Abstract

Betahistine has been used in the treatment of diseases accompanied by impaired peripheral circulation, e.g. Méniѐre’s syndrome, to reduce the frequency of episodes of vertigo and tinnitus. The drug has a short half-life and should be taken three times daily. Its contraindication in patients with peptic ulcer history and the difficulty of frequently dosing requires administration ways other than the oral route. The aim of this study was to prepare transdermal therapeutic system formulations containing betahistine by using synthetic and FDA approved polymers, Eudragit RL 100 and Eudragit RS 100. All the ingredients were evaluated for their excipient-drug compatibility, using Differantial Scanning Calorimetry (DSC) tests. Formulations with different excipient ratios were prepared and evaluated for their macroscopic properties (general appearance, homogeneity, flexibility, transparency and color). Results indicated that there was no incompatibility between drug and excipients. Excipient ratios were optimised according to the macroscopic properties of the formulations

Keywords

• Betahistine
• transdermal therapeutic system
• DSC
• Eudragit

References

1. James AL, Burton MJ. Betahistine for Meniere’s disease or syndrome. Cochrane Database of Systematic Reviews 2001, Issue 1. [Art. No.: CD001873. DOI: 10.1002/14651858.CD001873]
2. Watanabe I. Incidence of Meniere’s disease, including some other epidemiological data. In: Oosterveld WJ editor(s). Meniere’s Disease: A Comprehensive Appraisal. Chichester: John Wiley and Sons Ltd, 1983: 9–23.
3. Solvay Healthcare Limited. Serc8, Serc16. ABPI Compendium of Data Sheets. 1999-2000. London:Datapharm Publications Ltd, 1999:1629.
4. Wilmot TJ, Menon GN. Betahistine (SERC) in Meniere’s disease. J Laryngol Otol 1976; 90: 833-40.
5. Weiser M, Strösser W, Klein P. Homeopatic vs Conventional Treatment of Vertigo. Arch Otolaryngol Head and Neck Surg.1998; 124: 879-885.
6. Aantaa E. Treatment of Acute Vestibular Vertigo. Acta Otolaryngol (Stockh). 1991; Suppl 479: 44-47.
7. Kubicek WG, Anderson WD. Blood flow changes into the dog labyrinthine arteries. Paper presented at the American Academy of Ophthalmology and Otolaryngology, October-November 1967, Palmer House, Chicago, USA.
8. Martinez DM. The effects of Serc (betahistine hydrochloride) on the circulation of the inner ear in experimental animals. Acta Otolaryngol (Stockh) 1972; 74 (Suppl 305): 29-47.

9. Unemoto H, Sasa M, Takaori S, Ito J, Matsuoka 1. Inhibitory effect of betahistine on polysynaptic neurons in the lateral vestibular nucleus. Arch Otorhinolaryngol 1982; 236: 229-36.
10. Serc® Product Monograph, 2014.
11. Sweetman SC (Ed), (2007). Martindale: The Complete Drug Reference. 35 th Ed, Pharmaceutical Press, US
12. European Pharmacopoeia, 6th ed. Strasbourg: Council of Europe, 2007: 737-38.
13. Vinod KR, Sravani P, Banji D,Teja BB. Transdermal Drug Delıvery System –Overcoming Challenges Of Popular Drug Delivery Systems, Internatıonal Journal Of Pharma World Research, 2010; 1 (3): 1-14.
14. Wokovich AM, Prodduturi S, Doub WH, Hussain AS, Buhse LF. Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute. Eur. J. Pharm. Biopharm. 2006; 64 (1): 1-8.
15. Barry BW. Transdermal Drug Delivery. In: Aulton M, editor. Aulton’s Pharmaceutics. The Design and Manufacture of Medicines. Hungary: Churchill Livingstone, Elsevier, 2007; 565-97.
16. Flynn GL, Weiner ND. Topical and Transdermal Delivery-Provinces of Realism. In: Dermal and Transdermal Drug Delivery- New Insights and Perspectives, Eds: Gurny R, Teubner A, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 1993: 33-65.
17. Hadgraft J. Dermal and Transdermal Delivery. In: Modified Release Drug Delivery Technology, Eds: Rathbone MJ, Hadgraft J, Roberts MS, Marcel Dekker Inc, New York. 2003; 471-480.
18. Pfister WR. Transdermal and Dermal Therapeutic Systems: Current Status, Transdermal and Topical Drug Delivery Systems, Ghosh TK, Pfister WR, Yum SI, Interpharm Press, Illionis, USA, 1997; 33-112.
19. Kerimoğlu O, Keskin E, Dortunç B, Anah Ş. Matrix Type transdermal therapeutic system containing captopril: formulation optimization, in vitro and ex vivo characterization. Acta Pol Pharm. 2013; 70 (2): 291-300.
20. Verma PRP, Chandak AR. Development of matrix controlled transdermal delivery systems of pentazocine: In vitro/in vivo performance. Acta Pharm. 2009; 59: 171–186.
21. Gao Y, Liang J, Liu J, Xiao Y. Double-layer weekly sustained release transdermal patch containing gestodene and ethinylestradiol. Int. J. Pharm. 2009; 377 (1-2): 128-134.
22. Rowe RC, Sheskey PJ, Owen SC. (Eds), Handbook of Pharmaceutical Excipients, 5 th ed, Pharmaceutical Press and the American Pharmacists Association, London, UK. 2006.