Formulation Development and In Vitro Characterization of Zolmitriptan Controlled Release Drug Delivery Systems

© 2019 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )

Download PDF

Cite

XML

Abstract

Background: Zolmitriptan is an artificial tryptamine, employed for the acute cure of migraine attack with or exclusive
of aura and cluster headaches. Objective: It is an attempt to develop the extended release (ER) of Zolmitriptan matrix (ZMT) tablets to treat migraine safely and effectively.
Methods: All formulations were prepared with natural polymers or gums like guar gum, xanthan gum, karaya gum through direct compression method using 6mm punch.
Results: Powder blend of all formulations (F1 - F12) using different ratios of the above mentioned gums (5%, 10%, 15%
and 20%) were characterized with pre-compression parameters (angle of repose, bulk density, tapped density, compressibility index, hausner ratio, compatibility studies) and post-compression parameters (weight variation, thickness, friability, hardness, assay, in vitro dissolution studies). F1 - F4 formulations were prepared with gum karaya and compared with remaining gums; gum karaya shows more retardance capacity. F9 - F12 (with guar gum) formulations were unable to produce the desired release, whereas F5 - F8 formulations containing with xanthan gum exhibited more retarding effect with increasing concentration of polymer.
Conclusion: All prepared formulations (F1 - F12) were characterized and F3 formulation was optimized (97.3% drug released in 8 hours). All prepared formulations (F1 - F12) showed good flow properties and release patterns. Hence, formulations of ZMT matrix tablets have a promising delivery system which will enhance bio-availability and achieve greater therapeutic efficacy.

Keywords

Zolmitriptan

controlled release

direct compression

bio-availability

therapeutic efficacy

Conflict of interest

The authors declare no conflict of interest.

References

[1]

Kohrs, J.N.; Liyanage, T.; Don, A.; Venkatesan, N.; Najarzadeh, A.; Puleo, A.D. Drug delivery systems and controlled release. In: Encyclopedia of Biomedical Engineering. United States: Elsevier; 2018. p316-329. Doi:10.1016/b978-0-12-801238-3.11037-2.

[2]

Davoodi, P.; Lee, L.Y.; Xu, Q.; Sunil, V.; Sun, Y.; Soh, S.; Wang, C.H. Drug delivery systems for programmed and ondemand release. Adv. Drug Deliv. Rev., 2018, 132, 104-138.

[3]

Hardenia, A.; Maheshwari, N.; Hardenia, S.S.; Dwivedi, S.K.; Maheshwari, R.; Tekade, R.K. Scientific rationale for designing controlled drug delivery systems. In: Basic Fundamentals of Drug Delivery. Cambridge, MA, USA: Academic Press; 2019. p. 1-28.

[4]

George, A.; Shah, P.A.; Shrivastav, P.S. Guar gum: Versatile natural polymer for drug delivery applications. Eur. Polym. J.,2018.https://doi.org/10.1016/j.eurpolymj.2018.10.042.

[5]

Chien, Y.W. Controlled and modulated release drug delivery systems. Encyclopedia Pharm. Technol., New York: Marcel Dekker; 1990. p280-313.

[6]

Ritschel, W.A.; Kearns, G.L. Absorption/transport mechanisms. In: Ritschel, W.A.; Kearns, G.L.; editors. Handbook of Basic Pharmacokinetics Including Clinical Applications. Washington, DC: American Pharmaceutical Association; 1999. p. 63.

[7]

Togaru, V.; Venisetty, R.K.; Bakshi, V.; Jadi, R.K. Formulation development and in vitro evaluation of propranolol hydrochloride extended release matrix tablets. Emergent Life Sci. Res., 2017, 3(1), 38-47.

[8]

Jadi, R.K.; Bomma, R.; Sellappan, V. Development of a new single unit dosage form of propranolol HCl extended release noneffervescent floating matrix tablets: In vitro and in vivo evaluation. J. Appl. Pharm. Sci., 2016, 6(5), 112-118.

[9]

Subedi, R.K.; Ryoo, J.P.; Moon, C.; Choi, H.K. Influence of formulation variables in transdermal drug delivery system containing zolmitriptan. Int. J. Pharm., 2011, 419(1-2), 209-214.

[10]

Tuchman, M.; Hee, A.; Emeribe, U.; Silberstein, S. Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of menstrual migraine. CNS Drugs, 2006, 20(12), 1019-1026.

[11]

Mauskop, A.; Farkkila, M.; Hering-Hanit, R.; Rapopot, A.; Warner, J. Zolmitriptan is effective for the treatment of persistent and recurrent migraine headache. Curr. Med. Res. Opin., 1999, 15(4), 282-289.

[12]

Dowson, A.J.; MacGregor, E.A.; Purdy, R.A.; Becker, W.J.; Green, J.; Levy, S.L. Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine. Cephalalgia, 2002, 22(2), 101-106.

[13]

Tepper, S.J.; Donnan, G.A.; Dowson, A.J.; Bomhof, M.A.; Elkind, A.; Meloche, J.; Fletcher, P.E.; Millson, D.S. A long-term study to maximise migraine relief with zolmitriptan. Curr. Med. Res. Opin., 1999, 15(4), 254-271.

[14]

Lionetto, L.; Casolla, B.; Mastropietri, F.; D’Alonzo, L.; Negro, A.; Simmaco, M.; Martelletti, P. Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines. Expert Opin. Drug Metab. Toxicol., 2012, 8(8), 1043-1050.

[15]

Panda, N.; Reddy, A.V.; Reddy, G.S.; Panda, K.C. Formulation design and in vitro evaluation of zolmitriptan immediate release tablets using primojel and AC-Di-Sol. J. Pharm. Sci. Res., 2015, 7(8), 545-553.

[16]

Jadi, R.K.; Tatikonda, A.; Reedy, P.R.; Venisetty, R.K. Design and characterization of pregabalin swellable core osmotic pumps. Int. J. Pharm. Res. Allied Sci., 2016, 5(3), 8-15.

[17]

Prasad, R.R.; Kumar, J.R.; Vasudha, B.; Chettupalli, A.K. Formulation development and evaluation of allopurinol solid dispersions by solvent evaporation technique. Int. J. Appl. Pharm., 2018, 10(4), 168-171.

[18]

Bayrak, Z.; Tas, C.; Tasdemir, U.; Erol, H.; Ozkan, C.K.; Savaser, A.; Ozkan, Y. 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.

[19]

Mahmoud, A.A.; Salah, S. Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets. Drug Dev. Ind. Pharm., 2012, 38(6), 762-769.

[20]

Shiledar, R.R.; Tagalpallewar, A.A.; Kokare, C.R. Formulation and in vitro evaluation of xanthan gum-based bi-layered mucoadhesive buccal patches of zolmitriptan. Carbohydr. Polym., 2014, 101, 1234-1242.

[21]

Chen, G.L.; Hao, W.H. Factors affecting zero-order release kinetics of porous gelatine capsules. Drug Dev. Ind. Pharm., 1998, 24(6), 557-562.

[22]

Wagner, J.G. Interpretation of percent dissolved time plots derived from in vitro testing of conventional tablets and capsules. J. Pharm. Sci., 1969, 58(10), 1253-1257.

[23]

Higuchi, T. Mechanism of sustained action medication: Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52, 1145-1149.

[24]

Korsmeyer, R.W.; Gurny, R.; Doelker, E.; Buri, P.; Peppas, N.A. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm., 1983, 15, 25-35.

Previous article in this issue

Next article in this issue

INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823, Published by AccScience Publishing