Application of hydroxypropyl methylcellulose as a protective agent against magnesium stearate induced crystallization of amorphous itraconazole

B. Démuth, D. L. Galata, A. Balogh, E. Szabó, B. Nagy, A. Farkas, E. Hirsch, H. Pataki, T. Vigh, J. Mensch, G. Verreck, Z. K. Nagy, G. Marosi

Research output: Article

4 Citations (Scopus)

Abstract

Itraconazole is a fungicide drug which has low bioavailability due to its poor water solubility. Amorphous solid dispersion (ASD) is a tool that has the potential to greatly increase the dissolution rate and extent of compounds. In this work, the dissolution of tablets containing the ASD of itraconazole with either hydroxypropyl methylcellulose (HPMC) or vinylpyrrolidone-vinyl acetate copolymer (PVPVA) was compared in order to find a formulation which can prevent the drug from the precipitation caused by magnesium stearate. Formulations containing the PVPVA-based ASD with HPMC included in various forms could reach 90% dissolution in 2 h, while HPMC-based ASDs could release 100% of the drug. However, HPMC-based ASD had remarkably poor grindability and low bulk density, which limited its processability and applicability. The latter issue could be resolved by roller compacting the ASD, which significantly increases the bulk density and the flowability of the powder blends used for tableting. This roller compaction step might be a base for the industrial application of HPMC-based, electrospun ASDs.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume121
DOIs
Publication statusPublished - aug. 30 2018

Fingerprint

Protective Agents
Itraconazole
Crystallization
Pharmaceutical Preparations
Powders
Solubility
Biological Availability
Tablets
Hypromellose Derivatives
stearic acid
Water

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Application of hydroxypropyl methylcellulose as a protective agent against magnesium stearate induced crystallization of amorphous itraconazole. / Démuth, B.; Galata, D. L.; Balogh, A.; Szabó, E.; Nagy, B.; Farkas, A.; Hirsch, E.; Pataki, H.; Vigh, T.; Mensch, J.; Verreck, G.; Nagy, Z. K.; Marosi, G.

In: European Journal of Pharmaceutical Sciences, Vol. 121, 30.08.2018, p. 301-308.

Research output: Article

Démuth, B, Galata, DL, Balogh, A, Szabó, E, Nagy, B, Farkas, A, Hirsch, E, Pataki, H, Vigh, T, Mensch, J, Verreck, G, Nagy, ZK & Marosi, G 2018, 'Application of hydroxypropyl methylcellulose as a protective agent against magnesium stearate induced crystallization of amorphous itraconazole', European Journal of Pharmaceutical Sciences, vol. 121, pp. 301-308. https://doi.org/10.1016/j.ejps.2018.06.008
Démuth, B. ; Galata, D. L. ; Balogh, A. ; Szabó, E. ; Nagy, B. ; Farkas, A. ; Hirsch, E. ; Pataki, H. ; Vigh, T. ; Mensch, J. ; Verreck, G. ; Nagy, Z. K. ; Marosi, G. / Application of hydroxypropyl methylcellulose as a protective agent against magnesium stearate induced crystallization of amorphous itraconazole. In: European Journal of Pharmaceutical Sciences. 2018 ; Vol. 121. pp. 301-308.
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