Hygroscopic stability and dissolution properties of spray-dried solid dispersions of furosemide with Eudragit.
Spray-dried solid dispersions of furosemide-Eudragit RS100 and RL100 (ethyl methacrylate chlorotrimethylammoniumethyl methacrylate copolymer) were studied to determine their stability at 45 degrees C and 0, 44, and 75% relative humidity and their dissolution characteristics. The crystallization rates of the solid dispersions were measured by X-ray powder diffractometry and calculated on the basis of the Jander equation to estimate physicochemical stability in the presence of water vapor. The stability of the solid dispersion depended on the kind of acrylic resins and the drug content. The solid dispersion with a drug: Eudragit RL100 ratio of 1:3 was the most stable at 75% relative humidity. The dissolution profiles of the solid dispersions were measured in a pH 6.8 buffer at 37 degrees C. The equilibrium drug concentration of the solid dispersions were estimated from the dissolution profiles after 24 h. The equilibrium drug concentration decreased with an increasing Eudragit quaternary ammonium group: furosemide molar ratio. The equilibrium drug concentrations of the solid dispersions with > 0.3 mol of the quaternary ammonium group were approximately 0. Thus, the drug was completely adsorbed on Eudragit.
Otsuka
M
M
Department of Pharmaceutical Technology, Kobe Women's College of Pharmacy, Japan.
Onoe
M
M
Matsuda
Y
Y
D000180:Acrylic Resins; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D005583:Fourier Analysis; D005665:Furosemide / Q000008:administration & dosage / Q000737:chemistry*; D006813:Humidity; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011109:Polymethacrylic Acids; D011208:Powders; D012995:Solubility; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
D000180:Acrylic Resins; D011109:Polymethacrylic Acids; D011208:Powders; C038300:methylmethacrylate-methacrylic acid copolymer; D005665:Furosemide