溶出度方法学验证9概要1.pptVIP

* * * THE PHARMACOPIAL STATUS OF DISSOLUTION TESTING Compendial testing equipment Factors affecting test results Harmonization USP v EP v JP Calibration, chemical or mechanical Automation a blessing and a curse GENERAPHARM * The Apparatus Paddle or Basket * * Paddle v. Basket Problems with floating dosage units Problems with sticking dosage units Use of spiral for holding capsules is subject to variability with operators. The phenomenon of cone formation that results from nondispersion of disintegrated tablets can lead to nonreproducibility of test. Poor mechanical stability. Hindered visual inspection. Disintegration-dissolution interaction (slower disintegration keeps the dosage unit in a site of higher agitation, thus increasing dissolution). Poor homogeneity of the bulk fluid due to insufficient stirring or agitation. Sensitivity against external vibration, eccentricity and the presence of baffles such as thermometer or sampling tube. Inconvenience for cleaning the set-up after testing. Weaknesses of Paddle Method Weaknesses of Basket Method * Hydrodynamics and cone effects * Cone effects The cone effect is often seen with the paddle But it can also occur with the basket * The cone effect * Heavy granulate * Cone effect change of rpm CONE 50 rpm 75 rpm * Paddle design improvements USP Paddle Pitched blade * The peak vessel The Peak vessel may seem to be a good solution. However it can give very irreproducible results because there are many possible tablet orientations ranging from simple alignment in the trough through to tablets actually rolling round like a race track. Due to this it is possible to see significant differences in dissolution results when making slight changes in tablet geometry * Agitation Analysis of dissolution rates suggests a significant contribution from free convection in regions of low velocity at the base of the vessel of the basket apparatus. * USP basket Clip attachment official “O”