The Study of Oral Sustained Release Dosage Forms of Nifedipine by Matrix Concentration Gradient Method

• Main Author: 孟仲麟
• Other Authors: 王大鵬
• Format: Others
• Language: zh-TW
• Published: 1998
• Online Access: http://ndltd.ncl.edu.tw/handle/83745342388710674541

碩士 === 國防醫學院 === 藥學研究所 === 86 === 　　Nifedipine, a calcium channel-blocking agent, has widely been used for the treatment of hypertention and coronary heart disease. Because it's half-life is 2-3 hours, we can take the long-term sustained release dosage form to increase the duration and avoid the suddenly change of plasma drug concentration. 　　The objective of this study was to use the non-uniform drug concentration method for preparing oral dosage form of nifedipine with zero-order release. We use two peristaltic pumps, one pumps the matrix solution of vessel A to vessel B, which contains the nifedipine and matrix solution (the pump rate is Ki). The other one pumps drug solution from vessel B to the rotary fluid-bed (the pump rate is Ko). 　　The main formulation parameters we discuss are (1) the content of ethylcellulose (2) the incorporate amount of water soluble sucrose (3) the change of pump ratio Ki/(Ko-Ki). The dissolution test follow the USP X X III paddle method and use 1.5% (w/v) Tween 80 in the dissolution medium to maintain "sink condition". From the drug dissolution profile, we use the zero-order fitting model and the final release percent of nifedipine within 12 hours as the criteria to optimize the formulation. 　　The data indicate that (1) Increase of ethylcellulose amount will decrease the dissolution release rate constant when we fix the pump ratio. (2) Incorporation of water soluble sucrose will increase the total drug release percent, and the zero-order linearity is not change significantly. (3) Increase of pump ratio will decrease the release rate constant. Finally, we successfully select a formulation which correlation coefficient is 0.99055 and the final release percent is up pto 85%. In animal tests, proved that our sustained release formulation was successfully.