Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate.
Determination of drug-polymer miscibility is critical for successful development of solid dispersions. This report details a practical method to predict miscibility and physical stability of drug with various polymers in solid dispersion and, especially, in melt extrudates by applying a film-casting technique. Mixtures of itraconazole (ITZ) with hydroxypropylmethylcellulose phthalate (HPMCP), Kollidon(®) VA 64, Eudragit(®) E PO, and Soluplus(®) were film-casted, exposed to 40°C/75% RH for 1 month and then analyzed using differential scanning calorimetry (DSC), powder X-ray diffractometry, and polarized light microscopy (PLM). ITZ had the highest miscibility with HPMCP, being miscible at drug to polymer ratio of 6:4 (w/w). There was a downward trend of lower miscibility with Soluplus(®) (miscible at 3:7, w/w, and a few microcrystals present at 4:6, w/w), Kollidon(®) VA 64 (2:8, w/w) and Eudragit(®) E PO (<1:9, w/w). PLM was found more sensitive to detect drug crystallization than DSC and powder X-ray diffractometry. There was general correlation between results of film casting and hot-melt extrusion (HME) using a twin screw extruder. For ITZ-Soluplus(®) mixtures, HME at 4:6 (w/w) resulted in a single phase, whereas drug crystallization was observed at higher drug load. HME of ITZ-Kollidon(®) VA 64 mixtures also correlated well with the miscibility predicted by film casting.
College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.
Tapan
T
Parikh
College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.
Simerdeep Singh
SS
Gupta
College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.
Anuprabha K
AK
Meena
Catalent Pharma Solutions, Somerset, New Jersey, 08873.
Imre
I
Vitez
Catalent Pharma Solutions, Somerset, New Jersey, 08873.
Nidhi
N
Mahajan
College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.
Abu T M
AT
Serajuddin
D002152:Calorimetry, Differential Scanning / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D006358:Hot Temperature; D017964:Itraconazole / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008768:Methylmethacrylates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility
D008768:Methylmethacrylates; D011108:Polymers; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; C102808:Eudragit-E; D017964:Itraconazole; D011092:Polyethylene Glycols; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D011205:Povidone
amorphous; crystallization; drug-polymer miscibility; film casting; hot-melt extrusion; itraconazole; polarized light microscopy; polymer; solid dispersion; thermal analysis