This test is provided to determine compliance with the dissolution requirements for solid dosage forms administered orally. In this chapter, a dosage unit is defined as 1 tablet or 1 capsule or the amount specified.
APPARATUS
Apparatus 1 (Basket apparatus)
The assembly consists of the following:
a vessel, which may be covered, made of glass or other inert, transparent material;
a motor;
a drive shaft;
a cylindrical basket (stirring element).
- The vessel is partially immersed in a suitable water-bath of any convenient size or heated by a suitable device such as a heating jacket. The water-bath or heating device permits maintaining the temperature inside the vessel at 37 ± 0.5 °C during the test and keeping the dissolution medium in constant, smooth motion.
- No part of the assembly, including the environment in which the assembly is placed, contributes significant motion, agitation, or vibration beyond that due to the smoothly rotating stirring element.
- Apparatus that permits observation of the preparation and stirring element during the test is preferable. The vessel is cylindrical, with a hemispherical bottom and a capacity of 1 litre. Its height is 160-210 mm and its inside diameter is 98-106 mm. Its sides are flanged at the top. A fitted cover may be used to retard evaporation.
- The shaft is positioned so that its axis is not more than 2 mm at any point from the vertical axis of the vessel and rotates smoothly and without significant wobble that could affect the results. A speed-regulating device is used that allows the shaft rotation speed to be selected and maintained at a specified rate, within ± 4%.
- Shaft and basket components of the stirring element are fabricated of stainless steel, type 316 or equivalent, to the specifications shown in Figure -1.
- A basket having a gold coating of about 2.5 µm (0.0001 inch) thick may be used. The dosage unit is placed in a dry basket at the beginning of each test. The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 ± 2 mm during the test.
Apparatus 2 (Paddle apparatus)
- Use the assembly from Apparatus 1, except that a paddle formed from a blade and a shaft is used as the stirring element. The shaft is positioned so that its axis is not more than 2 mm from the vertical axis of the vessel, at any point, and rotates smoothly without significant wobble that could affect the results.
- The vertical center line of the blade passes through the axis of the shaft so that the bottom of the blade is flush with the bottom of the shaft. The paddle conforms to the specifications shown in Figure-2.
- The distance of 25 ± 2 mm between the bottom of the blade and the inside bottom of the vessel is maintained during the test. The metallic or suitably inert, rigid blade and shaft comprise a single entity.
- A suitable two-part detachable design may be used provided the assembly remains firmly engaged during the test. The paddle blade and shaft may be coated with a suitable coating so as to make them inert. The dosage unit is allowed to sink to the bottom of the vessel before rotation of the blade is started.
- A small, loose piece of non-reactive material, such as not more than a few turns of wire helix, may be attached to dosage units that would otherwise float. An alternative sinker device is shown in Figure-3.
Apparatus 3 (Reciprocating cylinder)
- The assembly consists of a set of cylindrical, flat-bottomed glass vessels; a set of glass reciprocating cylinders; inert fittings (stainless steel type 316 or other suitable material) and screens that are made of suitable nonsorbing and nonreactive material, and that are designed to fit the tops and bottoms of the reciprocating cylinders; a motor and drive assembly to reciprocate the cylinders vertically inside the vessels, and if desired, index the reciprocating cylinders horizontally to a different row of vessels.
- The vessels are partially immersed in a suitable water bath of any convenient size that permits holding the temperature at 37 ± 0.5 °C during the test. No part of the assembly, including the environment in which the assembly is placed, contributes significant motion, agitation, or vibration beyond that due to the smooth, vertically reciprocating cylinder.
- A device is used that allows the reciprocation rate to be selected and maintained at the specified dip rate, within ± 5 percent. An apparatus that permits observation of the preparations and reciprocating cylinders is preferable. The vessels are provided with an evaporation cap that remains in place for the duration of the test. The components conform to the dimensions shown in Figure-4 unless otherwise specified.
Apparatus 4 (Flow-through cell)
The assembly consists of
a reservoir and a pump for the dissolution medium;
a flow-through cell;
a water bath that maintains the dissolution medium at 37 ± 0.5 °C. Use the specified cell size.
- The pump forces the dissolution medium upwards through the flow-through cell. The pump has a delivery range between 240 mL/h and 960 mL/h, with standard flow rates of 4 mL/min, 8 mL/min, and 16 mL/min. It must deliver a constant flow (± 5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 ± 10 pulses/min. A pump without pulsation may also be used. Dissolution test procedures using the flow-through cell must be characterized with respect to rate and any pulsation.
- The flow-through cell (see Figures 2.9.3.-5 and 2.9.3.-6) of transparent and inert material is mounted vertically, with a filter system that prevents the escape of undissolved particles from the top of the cell; standard cell diameters are 12 mm and 22.6 mm; the bottom cone is usually filled with small glass beads of about 1 mm diameter, with 1 bead of about 5 mm positioned at the apex to protect the fluid entry tube; a tablet holder (see Figures -5 and -6) is available for positioning of special dosage forms. The cell is immersed in a water bath, and the temperature is maintained at 37 ± 0.5 °C.
- The apparatus uses a clamp mechanism and 2 O-rings for the fixation of the cell assembly. The pump is separated from the dissolution unit in order to shield the latter against any vibrations originating from the pump. The position of the pump must not be on a level higher than the reservoir flasks. Tube connections are as short as possible. Use suitably inert tubing, such as polytetrafluoroethylene, with a 1.6 mm inner diameter and inert flanged-end connections.
Determine the acceptable performance of the dissolution test assembly periodically.
Tags
Quality Control
