Influence of preparation methods on solid state supersaturation of amorphous solid dispersions: a case study with itraconazole and eudragit e100.
OBJECTIVE
The present study aims to determine the drug / polymer miscibility level as a function of the preparation method for an amorphous solid dispersion model system containing itraconazole and eudragit E100. This value was compared to the theoretical crystalline drug solubility in the amorphous polymer and the miscibility of the amorphous drug in the amorphous polymer.


METHODS
The amorphous solid dispersions were prepared via spray drying and film casting in order to evaluate the influence of the solvent drying rate. The experimental miscibility level was estimated using XRPD, MDSC, FT-IR, HPLC and TGA. The solubility and miscibility were estimated using the Flory-Huggins mixing theory and experimental drug in monomer solubility data.


RESULTS
The experimental miscibility level was found to be 27.5% w/w for spray-dried and 15% for film-casted solid dispersions. FT-IR measurements confirmed the absence of saturable interactions like hydrogen bonds, and analysis of the mixed glass transition temperatures suggested low adhesion forces in the amorphous mixture. The solubility analysis rendered a positive FH interaction parameter, a crystalline solubility of approximately 0.012% w/w and an amorphous drug-polymer miscibility of approximately 7.07% w/w.


CONCLUSIONS
The solid dispersions are significantly supersaturated with respect to both crystalline solubility and amorphous miscibility demonstrating the influence of manufacturing methodology.
Janssens
Sandrien
S
Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Herestraat 49, bus 921, 3000, Leuven, Belgium.
De Zeure
Ann
A
Paudel
Amrit
A
Van Humbeeck
Jan
J
Rombaut
Patrick
P
Van den Mooter
Guy
G
D000179:Acrylates; D000465:Algorithms; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003890:Desiccation; D005079:Excipients; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D000179:Acrylates; D000935:Antifungal Agents; C477020:Eudragit E100; D005079:Excipients; D011108:Polymers; D017964:Itraconazole