1087 INTRINSIC DISSOLUTION

Apparatus— A typical apparatus consists of a punch and die fabricated out of hardened steel. The base of the die has three threaded holes for the attachment of a surface plate made of polished steel, providing a mirror-smooth base for the compacted pellet. The die has a 0.1-cm to 1.0-cm diameter cavity into which is placed a measured amount of the material whose intrinsic dissolution rate is to be determined. The punch is then inserted in the die cavity and the test material is compressed with a benchtop tablet press. [NOTE—A hole through the head of the punch allows insertion of the metal rod to facilitate removal from the die after the test.] A compacted pellet of the material is formed in the cavity with a single face of defined area exposed on the bottom of the die (see accompanying figure). The bottom of the die cavity is threaded so that at least 50% to 75% of the compacted pellet can dissolve without its falling out of the die. The top of the die has a threaded shoulder that allows it to be attached to a holder. The holder is mounted on a laboratory stirring device, and the entire die, with the compacted pellet still in place, is immersed in the dissolution medium and rotated by the stirring device (see Dissolution 711).

Test Preparation— Weigh the material to be tested onto a piece of tared weighing paper. Attach the surface plate to the underside of the die, and secure it with the three screws provided. Transfer the accurately weighed portion of the material under test into the die cavity. Place the punch into the chamber, and secure the metal plate on top of the assembly. Compress the powder on a hydraulic press for 1 minute at the minimum compression pressure necessary to form a nondisintegrating compacted pellet. Detach the surface plate, and screw the die with punch still in place into the holder. Tighten securely. Remove all loose powder from the surface of the die by blowing compressed air or nitrogen.

Procedure— Slide the die-holder assembly into the dissolution test chuck, and tighten. Position the shaft in the spindle so that when the tested head is lowered, the exposed surface of the compacted pellet will be 3.8 cm from the bottom of the vessel. The disk assembly should be aligned to minimize wobble, and air bubbles should not be allowed to form on the compacted pellet or die surface as this could alter fluid flow. [NOTE—Air bubbles may be avoided by using an apparatus with a different configuration, such as a die holder that holds the compacted pellet in a fixed vertical position with agitation provided by a paddle positioned 6 mm from the surface of the pellet.] Perform the analysis as directed in the individual monograph. If possible, sink conditions should be maintained throughout the test. The data for the cumulative amount dissolved at each time point should be corrected for sampling losses. To calculate the intrinsic dissolution rate, plot the cumulative amount of test specimen dissolved per unit area of the compacted pellet against time until 10% is dissolved. The cumulative amount dissolved per unit area is given by the cumulative amount dissolved at each time point divided by the surface area exposed (0.5 cm2). Linear regression should then be performed on data points up to and including the time point beyond which 10% is dissolved. The intrinsic dissolution rate of the test specimen, in mg per minute per cm2, is determined from the slope of the regression line.

Auxiliary Information— Staff Liaison : Horacio Pappa, Ph.D. Pharmacopeial Forum : Volume No. 30(6) Page 2130