Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion.
Poly(ethylene oxide) (PEO) as a drug carrier in hot-melt extrusion was studied by using a model drug, nifedipine, in a twin-screw extruder. Binary mixtures of PEO and nifedipine have been shown to be amenable to hot-melting at a temperature as low as 70 degrees C, well below nifedipine's melting point (172 degrees C). Hot-stage microscopy provided visual evidence that nifedipine can form a miscible dispersion with PEO at 120 degrees C. Complete loss of nifedipine crystallinity when extrudated at and above 120 degrees C with a drug loading of 20% (w/w) was further confirmed by differential scanning calorimetry (DSC) and X-ray diffraction. Cross-sectional imaging of the extrudates using scanning electron microscopy indicated homogeneous drug distribution inside PEO when the processing temperature was above 120 degrees C. Raman spectroscopy confirmed drug-PEO interactions at a molecular level. Cryo-milled extrudates showed significant improvement in dissolution rate compared to either pure nifedipine or the physical mixture of PEO and nifedipine. A state of supersaturation was achieved after 10-minute release in pH 6.8 phosphate buffer. Finally, stability study demonstrated that the solid dispersion system is chemically stable for at least 3 months under the conditions of both 25 degrees C/60% RH and 40 degrees C/75% RH. Overall, PEO appears to be a promising aid/carrier to solublize poorly soluble drugs through the formation of solid dispersion via hot-melt extrusion, thereby improving dissolution and absorption.
Li
Lei
L
Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
AbuBaker
Omar
O
Shao
Zezhi J
ZJ
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004337:Drug Carriers; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning; D009543:Nifedipine / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012995:Solubility; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
D004337:Drug Carriers; D011092:Polyethylene Glycols; D009543:Nifedipine