As per USP Guideline,

Dissolution is the process in which a substance forms a solution. Dissolution testing measures the extent and rate of solution formation from a dosage form, such as tablet, capsule, ointment, etc. The dissolution of a drug is important for its bioavailability and therapeutic effectiveness.

A dissolution test uses an apparatus with specific test conditions in combination with acceptance criteria to evaluate the performance of the product. General chapter <711> Dissolution includes 4 standardized apparatus: basket, paddle, reciprocating cylinder, and flow-through cell.

 

Apparatus 1 (Basket)

The assembly (Apparatus 1) consists of the following: a vessel, which may be covered, and made of glass or other inert, transparent material; a motor; a metallic drive shaft; and a cylindrical basket. 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 holding the temperature inside the vessel at 37 ± 0.5°C during the test and keeps the bath fluid 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. An apparatus that permits observation of the specimen and of the stirring element during the test is preferable. The vessel is cylindrical, with a hemispherical bottom and with one of the following dimensions and capacities: for a nominal capacity of 1 L, the height is 160–210 mm, and its inside diameter is 98–106 mm; for a nominal capacity of 2 L, the height is 280–300 mm, and its inside diameter is 98–106 mm; and for a nominal capacity of 4 L, the height is 280–300 mm, and its inside diameter is 145–155 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 the specified rate given in the individual monograph within ±4%.

Shaft and basket components of the stirring element are fabricated of stainless steel, type 316, or other inert material, to the specifications. A basket having a gold coating of about 0.0001 inch (2.5 ยตm) thick may be used. A 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)

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 below. 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 compose a single entity. A suitable two-part, detachable design may be used, provided that the assembly remains firmly engaged during the test. The paddle blade and shaft may be coated with a suitable coating so as to make both of 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 nonreactive material, such as not more than a few turns of wire helix, may be attached to dosage units that would otherwise float. Other validated sinker devices may be used.


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; and a motor and drive assembly to reciprocate the cylinders vertically inside the vessels; 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 given in the individual monograph within ±5%. An apparatus that permits observation of the specimens and reciprocating cylinders is preferable. The vessels are provided with evaporation caps that remain in place for the duration of the test. The components conform to the dimensions shown below, unless otherwise specified in the individual monograph.



Apparatus 4 (Flow-Through Cell)

The assembly consists of a reservoir and a pump for the Dissolution medium; a §ow-through cell; and a water bath that maintains the Dissolution medium at 37 ± 0.5°. Use the specified cell size as given in the individual monograph.

The pump forces the Dissolution medium upward through the §ow-through cell. The pump has a delivery range between 240 and 960 mL/h, with standard §ow rates of 4, 8, 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 a flow-through cell must be characterized with respect to rate and any pulsation.

The flow-through cell, of transparent and inert material, is mounted vertically with a filter system (specified in the individual monograph) that prevents escape of undissolved particles from the top of the cell; standard cell diameters are 12 and 22.6 mm; the bottom cone is usually filled with small glass beads of about 1-mm diameter with one bead of about 5 mm, positioned at the apex to protect the fluid entry tube; and a tablet holder is available for positioning of special dosage forms, e.g., inlay tablets. The cell is immersed in a water bath, and the temperature is maintained at 37 ± 0.5°.


USP Apparatus 7 can be an excellent option for several types of unique dosage forms which require low volumes, gentle agitation, and/or media changes.  Pictured below are some holders available for a standard USP Apparatus 7.  These various holders can be used for various applications.

Small to medium sized transdermals can use the disks and cylinder in the below photo.  Solid oral dosage forms (including osmotics) can use the baskets and spring holders.  Osmotics tablets can also use the pointed rods, they are simply glued to the tip.  The baskets and the hook at the end can also be used for drug-eluting medical devices such as stents, pacemaker leads, etc.

Apparatus 7 can use volumes as low as 25mL with a standard Apparatus, and even as low as 3mL with the modified Apparatus 7 (400-DS from Agilent).  This makes Apparatus 7 ideal for low-dose products where quantitation is difficult or impossible in standard dissolution systems.

Mixing can vary from very gentle to robust in the Apparatus 7.  The stroke distance is only 2cm, and the dips per minute can be programmed across a wide range.

Media changes are possible through changes of rows in a traditional Apparatus 7 (same as with the Apparatus 3) or through media replacements (400-DS).

The Apparatus 7 is described in USP <724> Drug Release along with the Apparatus 5 and 6 which are primarily used for transdermals only.




The USP Apparatus 5 is referred to as the Paddle over Disk, and is defined in USP <724>.  This apparatus is primarily used for small to medium size transdermal patches, but it has been used for some other applications as well.  There are multiple diameter disks available depending on the size of the patch, and the paddle height would be set to 25mm +/- 2mm from the disk.
For transdermals, the sticky size of the patch is attached to a membrane and then placed on the disk with the membrane side facing up.  As with other transdermal approaches, care must be taken to ensure there are no air bubbles trapped between the patch and the membrane.  Transdermal dissolution methods are usually done at 32 degrees Celsius to mimic skin temperature.

I have also seen the Apparatus 5 used in two other situations.  One is using the disk as a sinker for dosage forms that swell beyond the size of standard sinkers - although I do not feel this is a preferred approach.

The other way I will see this used is for dissolving films.  These quick dissolving films can be placed onto the mesh backing of the Apparatus 5 - or even sandwiched between 2 mesh screens - and used for dissolution testing.  For these films, the apparatus 5 allows for reproducible sample placement.  These films are typically designed to dissolve in the mouth - so they often are 10 minutes or less until complete dissolution has occurred.



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