Pharmaceutical aspects of the development of the drug Clivas, tablets: quality, stability and safety | Ukrainian Medical Journal

The aim of the study was the pharmaceutical development of the drug rosuvastatin calcium (Clivas) in the form of 10 mg and 20 mg film-coated tablets [1, 2]. The main task was to create an optimal composition based on the amorphous form of the active pharmaceutical ingredient using certain excipients to improve solubility and ensure proper stability of the drug. At the time of the study, the composition of the reference drug is protected by patents in Ukraine and European countries [3]. During the development, a comparative analysis of the composition of the reference drug Crestor® and existing generic drugs was carried out, as well as experimental studies on the selection of excipients and technological parameters. It has been established that the use of mannitol as a filler in combination with alkaline stabilizers (magnesium hydroxide, calcium carbonate, sodium carbonate) contributes to increased stability and reduced formation of degradation products. The use of direct compression technology and primary packaging in Alu-Alu blisters additionally ensures the stability of the drug.

References

1. Інструкція для медичного застосування лікарського засобу Клівас 10 (Сlivas 10). http://www.drlz.com.ua.
2. Інструкція для медичного застосування лікарського засобу Клівас 20 (Сlivas 20). http://www.drlz.com.ua.
3. Bilgic M. (2010) Stable pharmaceutical compositions containing rosuvastatin calcium. Міжнар. пат. WO 2010/140992 A1 (PCT/TR2010/000103).
4. Boekholdt S.M., Hovingh G.K., Mora S. et al. (2014) Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J. Am. Coll. Cardiol., 64(5): 485–494. doi: 10.1016/j.jacc.2014.02.615.
5. Mach F., Baigent C., Alberico L. et al.; ESC Scientific Document Group (2020) 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur. Heart J., 41(1): 111–188. doi.org/10.1093/eurheartj/ehz455.
6. Belozerova N.M., Bilski P., Jarek M. et al. (2020) Exploring the molecular reorientations in amorphous rosuvastatin calcium. RSC Adv., 10(55): 33585–33594. doi: 10.1039/d0ra06108e.
7. Nissen S.E., Nicholls S.J., Sipahi I. et al. (2006) Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis: The ASTEROID Trial. JAMA, 295(13): 1556–1565. doi: 10.1001/jama.295.13.jpc60002.
8. European Pharmacopoeia (Ph. Eur.) Monograph 2631. Rosuvastatin Calcium. http://www.edqm.eu.
9. patents.google.com/patent/WO2010081861A1/ja.
10. González R., Peña M.Á., Torres N.S. et al. (2022) Design, development, and characterization of amorphous rosuvastatin calcium tablets. PLoS One, 17(3): e0265263. doi: 10.1371/journal.pone.0265263.
11. Santi G., Lazzari G. (2015) Stable pharmaceutical compositions containing an HMG-CoA reductase inhibitor. Міжнар. пат. WO 2005/023779 A1 (PCT/EP2004/009664).
12. Kondo H., Inoue H. (2014) Stabilized pharmaceutical composition. Міжнар. пат. WO 2014/050874 A1 (PCT/JP2013/075890). Дата подачі: 25.09.2013; дата публікації: 03.04.2014. WIPO.
13. Kondo H., Inoue H. (2017) Stabilized pharmaceutical composition. Міжнар. пат. WO 2017/183040 A1 (PCT/JP2017/013727). Дата подачі: 31.03.2017; дата публікації: 26.10.2017. WIPO.
14. Zakowiecki D., Hess T., Cal K. et al. (2022) Directly compressible formulation of immediate release rosuvastatin calcium tablets stabilized with tribasic calcium phosphate. Pharmaceutical Development and Technology, 27(4): 425–434. doi.org/10.1080/10837450.2022.2073370.
15. Furquan K., Zahid Z., Moizul H. et al. (2020). Stabilization of Rosuvastatin Calcium Formulation by Prevention of Intermolecular Esterification: An Experimental Design. Int. J. Pharm. Invest., 10: 192–196. doi: 10.5530/ijpi.2020.2.35.
16. González R., Peña M.Á., Torres N.S. et al. (2022) Design, development, and characterization of amorphous rosuvastatin calcium tablets. PLoS One, 17(3): e0265263. doi: 10.1371/journal.pone.0265263.
17. Інструкція для медичного застосування лікарського засобу КРЕСТОР (CRESTOR®).
18. Інструкція для медичного застосування лікарського засобу Розувастатин-Тева (Rosuvastatin-Teva).
19. Інструкція для медичного застосування лікарського засобу Роксера® (Roxera®).
20. Інструкція для медичного застосування лікарського засобу РОЗУКАРД®. mozdocs.kiev.ua.
21. ICH Q1B Photostability testing of new active substances and medicinal products — Scientific guideline, http://www.ema.europa.eu.
22. Bechard Simon R., Quraishi O., Kwong E. (1992) Film coating: effect of titanium dioxide concentration and film thickness on the photostability of nifedipine. Int. J. Pharm., 87: 133–139.