Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion—part I

• Published in: International journal of pharmaceutics 2003-01, Vol.251 (1), p.165-174
• Main Authors: Verreck, Geert, Six, Karel, Van den Mooter, Guy, Baert, Lieven, Peeters, Jef, Brewster, Marcus E.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; General pharmacology; Hypromellose Derivatives; Itraconazole; Itraconazole - analysis; Itraconazole - chemistry; Itraconazole - pharmacokinetics; Medical sciences; Melt extrusion; Methylcellulose - analogs & derivatives; Methylcellulose - analysis; Methylcellulose - chemistry; Methylcellulose - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solid dispersion; Technology, Pharmaceutical - methods
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00591-4

Solid dispersions containing different ratios of itraconazole and hydroxypropylmethylcellulose (HPMC) were prepared by solvent casting. Based on dose, differential scanning calorimetry and dissolution results, a drug/polymer ratio of 40/60 w/w was selected in order to prepare dispersions by melt extrusion. The melt extrusion process was characterized using a design of experiments (DOE) approach. All parameter settings resulted in the formation of an amorphous solid dispersion whereby HPMC 2910 5 mPa s prevents re-crystallization of the drug during cooling. Dissolution measurements demonstrated that a significantly increased dissolution rate was obtained with the amorphous solid dispersion compared to the physical mixture. The outcome of DOE further indicated that melt extrusion is very robust with regard to the itraconazole/HPMC melt extrudate characteristics. Stability studies demonstrated that the itraconazole/HPMC 40/60 w/w milled melt extrudate formulation is chemically and physically stable for periods in excess of 6 months as indicated by the absence of degradation products or re-crystallization of the drug.