Controlled release of furosemide from the ethylene-vinyl acetate matrix.
The ethylene-vinyl acetate (EVA) matrix containing furosemide was prepared by the casting method and the release patterns were observed. The solubility of furosemide was determined as a function of volume fraction of polyethylene glycol 400. The release of drug from the matrix was studied as a function of temperature and drug concentration. Plasticizers such as the citrates and the phthalates were added for preparing the membrane to increase the flexibility of the EVA matrix. The solubility of furosemide was the highest when the concentration of PEG 400 was 40% (v/v). The release rate of drug from the EVA matrix increased with increasing temperature and drug loading doses. A linear relationship was found between the release rate and the square root of the loading dose. The activation energy (Ea), which was measured from the slope of the logP versus 1000/T plots, was 12.33 kcal/mol for the 0.5% loading dose, and 11.58 kcal/mol for the 1.0% loading dose, and 11.00 kcal/mol for the 1.5% loading dose. Among the plasticizers used such as the citrates and the phthalates groups, diethyl phthalate showed the best enhancing effects in drug release. In conclusion, the application of an EVA matrix containing a plasticizer might be useful in the development of a controlled drug delivery system.
Cho
Cheong-Weon
CW
CJ Corp., R&D Center of Pharmaceuticals, Ichonsi, Gyonggido 467-812, South Korea.
Choi
Jun-Shik
JS
Shin
Sang-Chul
SC
D000279:Administration, Cutaneous; D002851:Chromatography, High Pressure Liquid; D002951:Citrates / Q000737:chemistry; D003692:Delayed-Action Preparations; D003993:Dibutyl Phthalate / Q000737:chemistry; D004232:Diuretics / Q000032:analysis / Q000737:chemistry*; D005665:Furosemide / Q000032:analysis / Q000737:chemistry*; D010795:Phthalic Acids / Q000737:chemistry; D010968:Plasticizers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility
D002951:Citrates; D003692:Delayed-Action Preparations; D004232:Diuretics; D010795:Phthalic Acids; D010968:Plasticizers; D011145:Polyvinyls; D003993:Dibutyl Phthalate; C016438:ethylenevinylacetate copolymer; D011092:Polyethylene Glycols; D005665:Furosemide; C007379:diethyl phthalate