Influence of Preparation Methods on Solid State Supersaturation of Amorphous Solid Dispersions: A Case Study with Itraconazole and Eudragit E100

Abstract

The solid dispersions are significantly supersaturated with respect to both crystalline solubility and amorphous miscibility demonstrating the influence of manufacturing methodology.

Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions

“…The Raman spectra of the ES, EB and SD samples could be very well approximated with the linear combinations of the reference spectra suggesting the absence of specific interactions between the ITR and polymer molecules, in accordance with earlier FT-IR results (Janssens et al, 2010). Clear evidence of phase separation was expected from the results of Raman mapping experiments.…”

“…In these works, the miscibility limit and phase separation of amorphous and crystalline ITR were investigated in melt extruded polymer systems in comparison with film casting and SD. The experimental miscibility limit (15% w/w when prepared by film casting or 27.5% w/w prepared by SD below the Tg of the polymer) was found to be strongly dependent on the manufacturing technology and higher value were achieved than expected based on theoretical study (7.07% w/w) (Janssens et al, 2010). Stability tests were not included in these experimental programs.…”

“…ITR is a well-known broad-spectrum antifungal agent (Glasmacher and Prentice, 2006) belonging to BCS II (Wu and Benet, 2005), the solid dispersions of which have been published with Eudragit E matrix by several authors (Janssens et al, 2010;Jung et al, 1999;Six et al, 2003). In these works, the miscibility limit and phase separation of amorphous and crystalline ITR were investigated in melt extruded polymer systems in comparison with film casting and SD.…”

Improved Supersaturation and Oral Absorption of Dutasteride by Amorphous Solid Dispersions

“…11,13,14) The Eudragit E solid dispersion with amorphous dutasteride formed a supersaturated solution with an apparent solubility above the equilibrium solubility and thus has an increased driving force for transport across biological membranes, such as the epithelial membrane within the GI tract, thereby increasing the bioavailability of dutasteride. 15,16) These results suggest that preparation of Eudragit E solid dispersion using a spraydrying process may be a promising approach for improving the bioavailability of dutasteride. However, future research should fully elucidate the physicochemical properties and stability of Eudragit E solid dispersions to help develop solid dosage forms.…”

Structural Characterization of Amorphous Solid Dispersions

“…• C; Janssens et al 2010). Instead, the respective enthalpy-recovery endotherms in NRHF signals facilitated the distinction of the T gm positions.…”