Formulation and characterization of ternary solid dispersions made up of Itraconazole and two excipients, TPGS 1000 and PVPVA 64, that were selected based on a supersaturation screening study.
Both d-alpha-tocopheryl polyethylene glycol 1000 (TPGS 1000) and polyvidone-vinylacetate 64 (PVPVA 64) provided an increase in the degree of supersaturation and stability of supersaturated Itraconazole solutions, compared to a blanc without excipient. Therefore, both components were combined as carrier in order to make ternary solid dispersions of Itraconazole by spray drying. This way, TPGS 1000 could be incorporated into a powder. Dissolution experiments on the ternary solid dispersions revealed that during the first hour the release was much higher than for the binary Itraconazole/PVPVA 64 solid dispersions. For some compositions a release of more than 80% was reached after 10min. However, after the first hour the drug started to precipitate. The ternary solid dispersions were all XRD amorphous, but MDSC revealed the coexistence of multiple amorphous phases and a crystalline Itraconazole phase, depending on the composition. Therefore the burst effect during the first hour can be ascribed to an accelerated dissolution of the amorphous Itraconazole fraction in the presence of TPGS 1000. The precipitation after 1h, however, is probably due to the combination of the surfactant properties of TPGS and the small crystalline Itraconazole fraction.
Janssens
Sandrien
S
Laboratorium voor Farmacotechnologie en Biofarmacie, Catholic University of Leuven, Leuven, Belgium.
Nagels
Sophie
S
Armas
Hector Novoa de
HN
D'Autry
Ward
W
Van Schepdael
Ann
A
Van den Mooter
Guy
G
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D004304:Dosage Forms; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D005079:Excipients / Q000008:administration & dosage*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D017964:Itraconazole / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011205:Povidone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011759:Pyrrolidines; D012995:Solubility; D013696:Temperature; D014753:Vinyl Compounds / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014961:X-Ray Diffraction
D004304:Dosage Forms; D005079:Excipients; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014810:Vitamin E; D017964:Itraconazole; D011092:Polyethylene Glycols; D011205:Povidone; C011566:vinyl acetate; C014225:tocophersolan