Tags

Type your tag names separated by a space and hit enter

Itraconazole/TPGS/Aerosil200 solid dispersions: characterization, physical stability and in vivo performance.
Eur J Pharm Sci. 2009 Oct 08; 38(3):270-8.EJ

Abstract

Solid dispersions were successfully prepared by co-spray-drying of TPGS-stabilized itraconazole nanosuspensions with Aerosil200, followed by heat treatment of the powders. The itraconazole/Aerosil200 weight ratios amounted to 50/50, 30/70, 40/60 and 20/80. The itraconazole content of the powders was close to the expected value, with relative errors between 0.3% and 7.8%. X-ray powder diffraction (XRPD), solid state NMR (SSNMR) and differential scanning calorimetry (DSC) evaluation on the powders revealed the formation of amorphous itraconazole and the absence of glassy itraconazole. Dissolution of the powders was enhanced compared to crystalline and glassy itraconazole (a 2-dimensional structured form of itraconazole). However, no clear trend could be observed between drug loading and dissolution performance of the solid dispersions. Upon storage, conversion to crystalline itraconazole was observed for the 50/50 powder based on XRPD, SSNMR and DSC measurements. Although the 40/60 powder remained X-ray amorphous upon storage, DSC did reveal that a small fraction (7.5+/-1.6% after 10 months of storage) of itraconazole crystallized upon storage. For the 30/70 and 20/80 dispersions, no crystallization could be seen. After 10 months of storage, important changes in the dissolution behavior of the powders were observed. A decrease in dissolution performance was seen for the 50/50 dispersion, which could be attributed to the crystallization of itraconazole. On the other hand, the 40/60, 30/70 and 20/80 dispersions showed an increase in dissolution rate (more than 60% after 10 min). Although not completely clear at this stage, adsorption of itraconazole onto the Aerosil200 surface during storage might be responsible for this behavior. Finally, in vivo experiments were performed in the rat. Oral bioavailability of the 30/70 dispersion was, although lower compared to the marketed Sporanox formulation, significantly enhanced compared to the crystalline drug.

Authors+Show Affiliations

Laboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19686846

Citation

Van Eerdenbrugh, Bernard, et al. "Itraconazole/TPGS/Aerosil200 Solid Dispersions: Characterization, Physical Stability and in Vivo Performance." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 38, no. 3, 2009, pp. 270-8.
Van Eerdenbrugh B, Van Speybroeck M, Mols R, et al. Itraconazole/TPGS/Aerosil200 solid dispersions: characterization, physical stability and in vivo performance. Eur J Pharm Sci. 2009;38(3):270-8.
Van Eerdenbrugh, B., Van Speybroeck, M., Mols, R., Houthoofd, K., Martens, J. A., Froyen, L., Van Humbeeck, J., Augustijns, P., & Van den Mooter, G. (2009). Itraconazole/TPGS/Aerosil200 solid dispersions: characterization, physical stability and in vivo performance. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 38(3), 270-8. https://doi.org/10.1016/j.ejps.2009.08.002
Van Eerdenbrugh B, et al. Itraconazole/TPGS/Aerosil200 Solid Dispersions: Characterization, Physical Stability and in Vivo Performance. Eur J Pharm Sci. 2009 Oct 8;38(3):270-8. PubMed PMID: 19686846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Itraconazole/TPGS/Aerosil200 solid dispersions: characterization, physical stability and in vivo performance. AU - Van Eerdenbrugh,Bernard, AU - Van Speybroeck,Michiel, AU - Mols,Raf, AU - Houthoofd,Kristof, AU - Martens,Johan A, AU - Froyen,Ludo, AU - Van Humbeeck,Jan, AU - Augustijns,Patrick, AU - Van den Mooter,Guy, Y1 - 2009/08/15/ PY - 2009/05/01/received PY - 2009/07/20/revised PY - 2009/08/10/accepted PY - 2009/8/19/entrez PY - 2009/8/19/pubmed PY - 2010/5/7/medline SP - 270 EP - 8 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 38 IS - 3 N2 - Solid dispersions were successfully prepared by co-spray-drying of TPGS-stabilized itraconazole nanosuspensions with Aerosil200, followed by heat treatment of the powders. The itraconazole/Aerosil200 weight ratios amounted to 50/50, 30/70, 40/60 and 20/80. The itraconazole content of the powders was close to the expected value, with relative errors between 0.3% and 7.8%. X-ray powder diffraction (XRPD), solid state NMR (SSNMR) and differential scanning calorimetry (DSC) evaluation on the powders revealed the formation of amorphous itraconazole and the absence of glassy itraconazole. Dissolution of the powders was enhanced compared to crystalline and glassy itraconazole (a 2-dimensional structured form of itraconazole). However, no clear trend could be observed between drug loading and dissolution performance of the solid dispersions. Upon storage, conversion to crystalline itraconazole was observed for the 50/50 powder based on XRPD, SSNMR and DSC measurements. Although the 40/60 powder remained X-ray amorphous upon storage, DSC did reveal that a small fraction (7.5+/-1.6% after 10 months of storage) of itraconazole crystallized upon storage. For the 30/70 and 20/80 dispersions, no crystallization could be seen. After 10 months of storage, important changes in the dissolution behavior of the powders were observed. A decrease in dissolution performance was seen for the 50/50 dispersion, which could be attributed to the crystallization of itraconazole. On the other hand, the 40/60, 30/70 and 20/80 dispersions showed an increase in dissolution rate (more than 60% after 10 min). Although not completely clear at this stage, adsorption of itraconazole onto the Aerosil200 surface during storage might be responsible for this behavior. Finally, in vivo experiments were performed in the rat. Oral bioavailability of the 30/70 dispersion was, although lower compared to the marketed Sporanox formulation, significantly enhanced compared to the crystalline drug. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/19686846/Itraconazole/TPGS/Aerosil200_solid_dispersions:_characterization_physical_stability_and_in_vivo_performance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(09)00235-8 DB - PRIME DP - Unbound Medicine ER -