Browse > Article
http://dx.doi.org/10.5352/JLS.2018.28.4.472

Compatibility Study of Excipients for Pravastatin Tablet  

Kim, Kang Min (Department of Pharmaceutical Science and Technology, Kyungsung University)
Publication Information
Journal of Life Science / v.28, no.4, 2018 , pp. 472-477 More about this Journal
Abstract
Pravastatin sodium is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia by reducing cholesterol biosynthesis. Pharmaceutical excipients of commonly used including water, diluents, stabilizers, disintegrants, lubricants and colorants, and were identified for compatibility. All tests were performed by means of physical mixture of pravastatin and the excipients, which were placed in a press-through-pack (PTP) and incubated under accelerated conditions ($40^{\circ}C$ and 75% relative humidity) for 3 months. The blends of pravastatin with all excipients developed white, off white, and light brown powders, which showed no changes upon visual analysis. Accelerated conditions changed the degradation profile of pravastatin calcium in the HPLC system when mixed with different excipients. Although most excipients can have minor effects on pravastatin stability, the major degradation product from pravastatin was lactone. Low-level interaction (assay and impurity) was induced by all excipients except for microcrystalline cellulose and croscarmellose sodium. These excipients increased lactone impurity in 3 months by as much as 0.22% and 0.18% respectively. The total mixture slightly increased the lactone impurity (by 0.43% in 3 months) of pravastatin. There was no change in the assays of all excipients. These results will be helpful in studying tablet size reductions for convenience of use.
Keywords
Compatibility; drug-excipient interaction; excipient; pravastatin;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Almeida, S., Filipe, A., Almeida, A., Gich, I., Antonijoan, R., Puntes, M., Barbanoj, M. and Caturla, M. C. 2006. Comparative study on the bioequivalence of two formulations of pravastatin. Arzneimittelforschung 56, 70-75.
2 Bharate, S. S., Bharate, S. B. and Bajaj, A. N. 2010. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J. Excip. Food Chem. 1, 3-26.
3 Brain-isasi, S., Requena, C. and Alvarez-lueje, A. 2008. Stability study of pravastatin under hydrolytic conditions assessed by HPLC. J. Chil. Chem. Soc. 53, 1684-1688.
4 Drug-excipient compatibility studies. 2014. http://pharmaquest.weebly.com/uploads/9/9/4/2/9942916/drug_excipient_compatibility_study.pdf
5 Gao, J., Fu, X., Ding, M. and Fu, Q. 2010. Studies on partial compatibility of PP and PS. Chin. J. Polym. Sci. 28, 647-656.   DOI
6 Hirano, T., Komuro, F., Furukawa, S., Nagano, S. and Takahashi, T. 1990. Effect of pravastatin sodium, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on very-low-density lipoprotein composition and kinetics in hyperlipidemia associated with experimental nephrosis. Metabolism 39, 605-609.   DOI
7 International Conference on Harmonisation (ICH) guideline. 2009. Pharmaceutical development Q8 (R2). Step 5 versions.
8 Jeong, Y. J., Kim, J. M., Jang, S. J., Bang, J. H., Jung, Y. G., Kim, S. T., Kang, S. H., Choi, J. I., Kim, S. S. and Kang, M. Y. 2017. The effect of pravastatin on insulin resistance in hyperglycemic patients. J. Kor. Diabetes 18, 53-61.   DOI
9 Kivisto, K. T., Grisk, O., Hofmann, U., Meissner, K., Moritz, K. U., Ritter, C., Arnold, K. A., Lutjoohann, D., von Bergmann, K., Kloting, I., Eichelbaum, M. and Kroemer, H. K. 2005. Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats. Drug Metab. Dispos. 33, 1593-1596.   DOI
10 Kim, K. M. and Kang, J. S. 2017. Design of experiments for coating process of valsartan and pravastatin fixed-dose combination tablet. Indian J. Pharm. Educ. 51, 128-135.   DOI
11 Malgorzata, P., Mohamed, S., Polonca, T. and Drago, K. 2010. Stability studies of cholesterol lowering statin drugs in aqueous samples using HPLC and LC-MS. Environ. Chem. Lett. 8 185-191.   DOI
12 Marian, E., Jurca, T., Kacso, I., Borodi, G., Rus, L. M. and Bratu, I. 2015. Compatibility study between simvastatin and excipients in their physical mixtures. Rev. Chim. 66, 803-807.
13 Ministry of Food and Drug Safety. 2015. http://www.mfds.go.kr/index.do?cd=&searchkey=title:contents&mid=914&pageNo=6&seq=22056&cmd=v
14 U.S. Pharmacopeia 31-NF 26, second supplement. 2008. http://www.uspnf.com/uspnf/pub/index?usp=31&nf=26&s=1
15 Ministry of Food and Drug Safety. Korean pharmacopoeia 11th. Notification No. 2017-63.
16 Rowe, R. C., Sheskey, P. J. and Owen, S. C. 2006. Handbook of pharmaceutical excipients. 5th ed. Pharmaceutical press, London, UK.
17 Sohn, Y. T. and Lee, A. K. 1999. Compatibility study using differential scanning calorimetry. J. Kor. Pharm. Sci. 29, 117-126.
18 U.S. Pharmacopeia 38-NF 33, 2015. The United States Pharmacopoeia, Rockville, MD: United States Pharmacopoeial Convention Inc., pp. 4966-4967.