FORMULATION OF RIZATRIPTAN BENZOATE SUBLINGUAL TABLETS PREPARED BY DIRECT COMPRESSION WITH DIFFERENT BIOADHESIVE POLYMER: IN VITRO AND EX VIVO EVALUATION
Â Objective: The current investigation deals with formulation and evaluation of fast disintegrating sublingual tablets of rizatriptan benzoate (RTB) to produce its intended therapeutic effect for acute treatment of migraine. When the drug is given by sublingual route, it overcomes the first pass metabolism and quick entry of drug in systemic circulation is obtained. It would result in fast pharmacological response hence faster relief from migraine which is an important criterion in migraine therapy.
Methods: In this study, RTB sublingual tablets were prepared using direct compression process using various bioadhesive polymers such as sodium carboxymethyl cellulose, hydroxyl propyl methyl cellulose-K4M, and chitosan at various concentration ranging 0.5-5% w/w along with sodium starch glycolate (SSG) or cross carmellose sodium (CCS) as super disintegrants at different concentration ranging 2-8% w/w.
Results: The tablets disintegrated quickly and dissolution tests conclude that RTB was released from the formulation within the compendial limits. The formulations batches (A8 and B8) containing 2% w/w chitosan along with 2% w/w SSG or CCS which disintegrate rapidly and show high dissolution and ex vivo permeation were selected as optimized formulations.
Conclusion: The results obtained from the study showed that the bioavailability problem of the drug has been solved as the drug is given by sublingual route and it directly enters into systemic circulation. Furthermore, the formulation overcomes the problems associated with migraine attack as fast disintegrating technology is used.
2. Verma H, Verma S, Prasad SB, Singh H. Sublingual delivery of Frovatriptan: An indication of potential alternative route. Int Sch Res Notices 2014;2014:675868.
3. Bredenberg S, Duberg M, LennernÃ¤s B, LennernÃ¤s H, Pettersson A, Westerberg M, et al. In vitro and in vivo evaluation of a new sublingual tablet system for rapid oromucosal absorption using fentanyl citrate as the active substance. Eur J Pharm Sci 2003;20(3):327-34.
4. Malkawi AH, Al-Ghananeem AM, Crooks PA. Development of a GC-MS assay for the determination of fentanyl pharmacokinetics in rabbit plasma after sublingual spray delivery. AAPS J 2008;10(2):261-7.
5. Wang Y, Zuo Z, Lee KK, Chow MS. Evaluation of HO-1-u-1 cell line as an in vitro model for sublingual drug delivery involving passive diffusion-initial validation studies. Int J Pharm 2007;334(1-2):27-34.
6. Senel S, Kremer MJ, Kas S, Wertz PW, Hincal AA, Squier CA. Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials 2000;21(20):2067-71.
7. Smart JD. Buccal drug delivery. Expert Opin Drug Deliv 2005;2(3):507-17.
8. Surapaneni MS, Das SK, Das NG. Effect of excipient and processing variables on adhesive properties and release profile of pentoxifylline from mucoadhesive tablets. Drug Dev Ind Pharm 2006;32(3):377-87.
9. Goswami T, Jasti B, Li X. Sublingual drug delivery. Crit Rev Ther Drug Carrier Syst 2008;25(5):449-84.
10. Wang Y, Zuo Z, Chow MS. HO-1-u-1 model for screening sublingual drug delivery-influence of pH, osmolarity and permeation enhancer. Int J Pharm 2009;370(1-2):68-74.
11. LÃ¡inez MJ. Rizatriptan in the treatment of migraine. Neuropsychiatr Dis Treat 2006;2(3):247-59.
12. Shirsat AE, Chitlange SS. Application of quality by design approach to optimize process and formulation parameters of rizatriptan loaded chitosan nanoparticles. J Adv Pharm Technol Res 2015;6(3):88-96.
13. Bayrak Z, Tas C, Tasdemir U, Erol H, Ozkan CK, Savaser A, et al. Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: In vitro and in vivo evaluation. Eur J Pharm Biopharm 2011;78(3):499-505.
14. Klancke J. Dissolution testing orally disintegrating tablets. Dissolut Technol 2003;10(2):6-8.
15. Pabari R, Ramtoola Z. Effect of a disintegration mechanism on wetting, water absorption, and disintegration time of orodispersible tablets. J Young Pharm 2012;4(3):157-63.
16. Marques MR, Loebenberg R, Almukainzi M. Simulated biological fluids with possible application in dissolution testing. Dissolut Technol 2011;18(3):15-28.
17. Shirsand SB, Suresh S, Swamy PV, Para MS, Nagendra Kumar D. Formulation design of fast disintegrating tablets using disintegrant blends. Indian J Pharm Sci 2010;72(1):130-3.
18. Prajapati ST, Patel PB, Patel CN. Formulation and evaluation of sublingual tablets containing Sumatriptan succinate. Int J Pharm Investig 2012;2(3):162-8.
19. Goswami T, Jasti BR, Li X. Estimation of the theoretical pore sizes of the porcine oral mucosa for permeation of hydrophilic permeants. Arch Oral Biol 2009;54(6):577-82.
20. Balusu H, Veerareddy PR. Formulation and evaluation of fast disintegrating Rizatriptan benzoate sublingual tablets. Malays J Pharm Sci 2012;10(1):45-60.
21. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline: Stability Testing of New Drug Substances and Products Q1A (R2). Available from: https://www.ich.org/fileadmin/ Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/ Q1A_R2__Guideline.pdf. [Last accessed on 2017 May 07].
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.