The Effect of Disintegrants and Mixing Method on Physicochemical Properties of Telmisartan
Abstract
Telmisartan (TMS) has a compact structure and is interlocked between crystal units. As a result, the substance has a high electrostatic force, which causes TMS to sintering when compressed into tablets. One method of overcoming sintering on TMS tablets is to add a disintegrant to the compressed tablet. The disintegrants used are derived from starch groups: Starch 1500® (S1500) and sodium starch glycolate (SSG), as well as microcrystalline cellulose (MCC) and croscarmellose sodium (CCS) groups. The purpose of this study was to examine the effects of several disintegrants on the dissolution and physicochemical properties of TMS with various treatments. TMS was varied with each disintegrant at a ratio of 1:9 % b/b. The treatment of TMS binary mixtures with various disintegrants includes physical mixtures, milled mixtures, compressed mixtures, and crushed compressed mixtures. Characterization and evaluation include PXRD and SEM testing as well as dissolution test. The characterization of PXRD and SEM in various treatments showed the effect of physicochemical properties on the TMS binary mixture with various disintegrants. The combination of TMS:CCS with a ratio of (1:9) resulted in the highest dissolution rate in all treatments.The treatment of the milled mixture produced the highest dissolution with DP60 minutes, which was around 55.86±2.47%. The addition of disintegrants to TMS with various treatments may reduce sintering but is not sufficient to meet the requirements for TMS dissolution, which dissolves within 30 minutes in phosphate buffer medium pH 7.5 with Q>75%.
References
telmisartan, using supercritical anti-solvent (SAS) process. Int J Pharm [Internet]. 2013;441(1–2):50–
5. Available from: http://dx.doi.org /10.1016/j.ijpharm.2012.12.020
2. Ahmed H, Shimpi MR, Velaga SP. Relationship between mechanical properties and crystal structure
in cocrystals and salt of paracetamol. Drug Dev Ind Pharm. 2017; 43(1):89–97.
3. Dinnebier RE, Sieger P, Nar H, Shankland K, David WIF. Structural characterization of three crystalline
modifications of telmisartan by single crystal and Jurnal Ilmu Kefarmasian Vol 19, 2021 Indonesia 203
high-resolution X-ray powder diff raction. J Pharm Sci.
2000; 89(11):1465–79.
4. Ratih, Pamudji, Alatas, Soewandhi 2018. Improving telmisartan mechanical properties through the
formation of telmisartan and oxalic acid co-crystal by using slow evaporation (SE) and ultrasound assisted
co-crystallization from solution (USSC) methods. Songklanakarin J Sci Technol. 2018;42(1):189–96.
5. Alatas F, Ratih H, Soewandhi SN. Enhancement of solubility and dissolution rate of telmisartan by
telmisartan-oxalic acid co-crystal formation. Int J Pharm Pharm Sci. 2015;7(3):423–6.
6. Wizel S, Kolatkar G, Tiqva P, Zisman E, Le R. Pharmaceutical composition of Telmisartan. Vol. 1, Patent Application Publication. 2009. p. 1–10.
7. Mohanachandran PS, Sindhumol PG, Kiran TS. Superdisintegrants: An overview. Int J Pharm Sci Rev
Res. 2011;6(1):105–9.
8. Desai PM, Liew CV, Heng PWS. Review of Disintegrants and the disintegration phenomena. J
Pharm Sci [Internet]. 2016;105(9):2545–55. Available from: http:// dx.doi.org/10.1016/j.xphs.2015.12.019
9. Bolhuis GK, Arends-Scholte AW, Stuut GJ, De Vries JA. Disintegration efficiency of sodium starch
glycolates, prepared from different native starches. Vol. 40. 1994. 317–320 p.
10. Young P, Edge S, Staniforth J, Steele DF, Price R . Dynamic Vapor Sorption Properties of
Sodium Starch Glycolate Disintegrants. PharmnDev Technol [Internet ]. 2 005;10(2):249–59.
Available from: http:// www.informaworld. com/openurl?genre=article&doi=10.1081/PDT-200054448
&magic= crossref% 7C%7CD404A21 C5B B053405B1A640AFFD44AE3
11. Rahman BM, Wahed MII, Khondkar P, Ahmed M, Islam R, Barman RK, et al. Eff ect of starch 1500 as a
binder and disintegrant in lamivudine tablets prepared by high shear wet granulation. Pak J Pharm Sci.
2008;21(4):455–9.
12. Priya V a V, Rao GCS, Reddy DS, Reddy VP. The eff ect of different superdisintegrants and their concentrations
on the dissolution of Topiramate immediate release tablets. Int J Pharm Sci Nanotechnol. 2009;2(2):531–6.
13. Xiong X, Xu K, Du Q, Zeng X, Xiao Y, Yang H, et al. Effects of temperature and solvent on the solid-state
transformations of Pranlukast during mechanical milling. J Pharm Sci [Internet]. 2017;106(6):1680–7. Available from: http://dx.doi.org/10.1016/j.xphs.2017.02.020
14. Qiu Z, Stowell JG, Cao W, Morris KR, Byrn SR, Carvajal MT. Effect of milling and compression on the solid-state Maillard reaction. J Pharm Sci.2005;94(11):2568–80.
15. Pawatekar TS, Rode RB. A review on sintering method in pharmaceutical sciences. 2014;4(2) :106–9.
16. Gould PL, Tan S Bin. The effect of recompression on the dissolution of wet massed tablets containing
superdisintegrants . Drug Dev Ind Pharm .1986;12:1929–45.
17. Zhao N, Augsburger LL. The influence of product brand-to-brand variability on superdisintegrant
performance: A case study with croscarmellose sodium. Pharm Dev Technol. 2006;11(2):179–85.
18. Edge S, Steele DF, Staniforth JN, Chen A, Woodcock PM. Powder compaction properties of sodium
starch glycolate disintegrants. Drug Dev Ind Pharm. 2002;28(8):989–99.
19. Maghsoodi M, Bakhsh AST. Evaluation of physicomechanical properties of drug-excipients agglomerates
obtained by crystallization. 2011;16(October 2009):243–9.
20. Faroongsarng D, Peck GE. The role of liquid water uptake by an insoluble tablet containing a disintegrant.
Drug Dev Ind Pharm. 1994;20(10):1777–94.
21. Gonnissen Y, Remon JP, Vervaet C. Development of directly compressible powders via co-spray drying. Eur
J Pharm Biopharm. 2007;67(1):220–6.
22. Wienen W, Entzeroth M, Meel JCA Van, Stangier J, Busch U, Ebner T, et al. A Review on Telmisartan :
A Novel , Long-Acting Angiotensin II-Receptor Antagonist. 2000; 18(2):127–54.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Licencing
All articles in Jurnal Ilmu Kefarmasian Indonesia are an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted non-commercial used, distribution and reproduction in any medium.
This licence applies to Author(s) and Public Reader means that the users mays :
- SHARE:
copy and redistribute the article in any medium or format - ADAPT:
remix, transform, and build upon the article (eg.: to produce a new research work and, possibly, a new publication) - ALIKE:
If you remix, transform, or build upon the article, you must distribute your contributions under the same license as the original. - NO ADDITIONAL RESTRICTIONS:
You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
It does however mean that when you use it you must:
- ATTRIBUTION: You must give appropriate credit to both the Author(s) and the journal, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
You may not:
- NONCOMMERCIAL: You may not use the article for commercial purposes.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Tools
