DOI QR코드

DOI QR Code

Preparation of Solid Dispersion of Everolimus in Gelucire 50/13 using Melt Granulation Technique for Enhanced Drug Release

  • Jang, Sun Woo ;
  • Choi, Young Wook ;
  • Kang, Myung Joo
  • Received : 2014.02.17
  • Accepted : 2014.03.03
  • Published : 2014.07.20

Abstract

Solid dispersion (SD) system of everolimus (EVR) with Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) was prepared using melt granulation technique with the aim of improving the physicochemical properties and dissolution rate. The solid state characterization using scanning electron microscopy and X-ray powder diffraction, indicated that the drug was homogeneously distributed in the surfactant carrier in a stable amorphous form. The dissolution rate of EVR from the optimized SD composed of the drug, Gelucire 50/13 and microcrystalline cellulose in a weight ratio of 1:5:10, was markedly rapid and higher than that from the drug powder and the market product (Afinitor$^{(R)}$, Novartis Pharmaceuticals) in all dissolution mediums tested from pH 3.0 to pH 6.8. The results of this study suggest that formulation of SD with Gelucire 50/13 using melt granulation procedure may be a simple and promising approach for improving the dissolution rate and oral absorption of the anti-cancer agent without the need for using an organic solvent.

Keywords

Everolimus;Solid dispersion;Gelucire 50/13;Dissolution;Melt granulation

References

  1. Yamashita, K.; Nakate, T.; Okimoto, K.; Ohike, A.; Tokunaga, Y.; Ibuki, R.; Higaki, K.; Kimura, T. Int. J. Pharm. 2003, 267, 79. https://doi.org/10.1016/j.ijpharm.2003.07.010
  2. Kohri, N.; Yamayoshi, Y.; Xin, H.; Iseki, K.; Sato, N.; Todo, S.; Miyazaki, K. J. Pharm. Pharmacol. 1999, 51, 159. https://doi.org/10.1211/0022357991772277
  3. Kobayashi, M.; Sada, N.; Sugawara, M.; Iseki, K.; Miyazaki, K. Int. J. Pharm. 2001, 221, 87. https://doi.org/10.1016/S0378-5173(01)00663-9
  4. ICH Harmonized tripartite guideline, Impurities: Guideline for Residual Solvents; The Fourth International Conference on Harmonization, 1997; p 17.
  5. Dressman, J. B.; Amidon, G. L.; Reppas, C.; Shah, V. P. Pharm. Res. 1998, 15, 11. https://doi.org/10.1023/A:1011984216775
  6. Horter, D.; Dressman, J. B. Adv. Drug Deliv. Rev. 2001, 46, 75. https://doi.org/10.1016/S0169-409X(00)00130-7
  7. Mosharraf, M.; Nystrom, C. Eur. J. Pharm. Sci. 1999, 9, 145. https://doi.org/10.1016/S0928-0987(99)00043-3
  8. EMEA, CHMP Assessment Report for Afinitor 1999.
  9. Novartis Pharmaceuticals Corporation, Afinitor (everolimus) Prescribing information 2013.
  10. Motzer, R. J.; Escudier, B.; Oudard, S.; Hutson, T. E.; Porta, C.; Bracarda, S.; Grunwald, V.; Thompson, J. A.; Figlin, R. A.; Hollaender, N.; Urbanowitz, G.; Berg, W. J.; Kay, A.; Lebwohl, D.; Ravaud, A. Lancet 2008, 372, 449. https://doi.org/10.1016/S0140-6736(08)61039-9
  11. FDA Clinical pharmacology and biopharmaceutics review 2006. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4183B1_02_08-FDA-ClinPharm- Original.pdf
  12. Patrice, G.; Barbara, H.; Rainer, L.; Friedrich, R. WO1997003654.
  13. Craig, D. Q. M. Int. J. Pharm. 2002, 231, 131. https://doi.org/10.1016/S0378-5173(01)00891-2
  14. Abdul-Fattah, A. M.; Bhargava, H. N. Int. J. Pharm. 2002, 235, 17. https://doi.org/10.1016/S0378-5173(01)00941-3
  15. Ainaoui, A.; Vergnaud, J. M. Int. J. Pharm. 1998, 169, 155. https://doi.org/10.1016/S0378-5173(98)00105-7
  16. Ainaoui, A.; Ouriemchi, E. M.; Bidah, D.; El-Amrani, M. K.; Vergnaud, J. M. J. Polym. Eng. 1997, 17, 245.
  17. Cavallari, C.; Rodriguez, L.; Albertini, B.; Passe-rini, N.; Rosetti, F.; Fini, A. J. Pharm. Sci. 2005, 94, 1124. https://doi.org/10.1002/jps.20337
  18. Dennis, A. B.; Farr, S. J.; Kellaway, I. W.; Taylor, G.; Davidson, R. Int. J. Pharm. 1990, 65, 85. https://doi.org/10.1016/0378-5173(90)90013-T
  19. El-Badry, M.; Fetih, G.; Fathy, M. Saudi Pharm. J. 2009, 17, 217. https://doi.org/10.1016/j.jsps.2009.08.006

Cited by

  1. Formulation of Nanoparticle Containing Everolimus Using Microfluidization and Freeze-Drying vol.64, pp.10, 2016, https://doi.org/10.1248/cpb.c16-00049
  2. New blends of hydroxypropylmethylcellulose and Gelucire 44/14: physical property and controlled release of drugs with different solubility pp.2093-6214, 2017, https://doi.org/10.1007/s40005-017-0322-z