711 dissolution (USP)

《

711

》

DISSOLUTION

This general chapter is harmonized with the corresponding texts of the

European Pharmacopoeia

and/or the

Japanese Pharmacopoeia.

These

pharmacopeias have undertaken not to make any unilateral change to this

harmonized chapter.

Portions of the present general chapter text that are national USP text, and

therefore not part of the harmonized text, are marked with symbols (

specify this fact.

This test is provided to determine compliance with the dissolution

requirements

where stated in the individual monograph

for dosage forms

) to

administered orally. In this general chapter, a dosage unit is defined as 1 tablet

or 1 capsule or the amount specified.

Of the types of apparatus described

herein, use the one specified in the individual monograph. Where the label

states that an article is enteric- coated, and where a dissolution or

disintegration test that does not specifically state that it is to be applied to

delayed-release articles is included in the individual monograph, the procedure

and interpretation given for

Delayed-Release Dosage Forms

is applied unless

otherwise specified in the individual monograph. For hard or soft gelatin

capsules and gelatin-coated tablets that do not conform to the

Dissolution

specification, repeat the test as follows. Where water or a medium with a pH of

less than 6.8 is specified as the

Medium

in the individual monograph, the same

Medium

specified may be used with the addition of purified pepsin that results

in an activity of 750,000 Units or less per 1000 mL. For media with a pH of 6.8

or greater, pancreatin can be added to produce not more than 1750 USP Units

of protease activity per 1000 mL.

USP Reference Standards

11

—

USP Chlorpheniramine Maleate

Extended-Release Tablets RS.

USP Prednisone Tablets RS. USP Salicylic

Acid Tablets RS.

1

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

1

; 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

during the test and keeping 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 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 mm to 210 mm and its inside diameter is 98 mm to 106 mm;

for a nominal capacity of 2 L, the height is 280 mm to 300 mm and its inside

diameter is 98 mm to 106 mm; and for a nominal capacity of 4 L, the height is

280 mm to 300 mm and its inside diameter is 145 mm to 155 mm

. Its sides

are flanged at the top. A fitted cover may be used to retard evaporation.

2

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 shown in

Figure 1.

A basket having a gold coating of about 0.0001 inch (2.5 ?

m) thick may be

2

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.

Figure 1. Basket Stirring Element

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 nonreactive material, such as not more than a

3

few turns of wire helix, may be attached to dosage units that would otherwise

float. An alternative sinker device is shown in

Figure 2a.

Other validated sinker

devices may be used.

Figure 2. Paddle Stirring Element

Figure 2a. Alternative sinker. All dimensions are expressed in mm.

Apparatus 3 (Reciprocating Cylinder)

NOT ACCEPTED BY THE JAPANESE PHARMACOPOEIA

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

4

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 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

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 an evaporation cap that remains in place for the duration of the

test. The components conform to the dimensions shown in

Figure 3

unless

otherwise specified

in the individual monograph

.

5

Figure 3. Apparatus 3 (reciprocating cylinder)

Apparatus 4 (Flow-Through Cell)

The assembly consists of a reservoir and a pump for the

Dissolution Medium;

a flow-through cell; and a water bath that maintains the

Dissolution Medium

at

6

37 ±

0.5

. Use the specified cell size

.

as given in the individual monograph

The pump forces the

Dissolution Medium

upwards through the flow-through

cell. The pump has a delivery range between 240 and 960 mL per hour, with

standard flow rates of 4, 8, and 16 mL per minute. It must deliver a constant

flow (±

5% of the nominal flow rate); the flow profile is sinusoidal with a

pulsation of 120 ±

10 pulses per minute.

The flow-through cell (see

Figures 4

and

5

), 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 (see

Figures 4

and

5

) is available for positioning of special dosage forms, for example, inlay

tablets. The cell is immersed in a water bath, and the temperature is

maintained at 37 ±

0.5

.

7

Figure 4. Large cell for tablets and capsules (top) Tablet holder for the large

cell (bottom) (All measurements are expressed in mm unless noted otherwise.)

8

Figure 5. Small cell for tablets and capsules (top) Tablet holder for the small

cell (bottom) (All measurements are expressed in mm unless noted otherwise.)

The apparatus uses a clamp mechanism and two O-rings to assemble the cell.

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

should not be on a level higher than the reservoir flasks. Tube connections are

as short as possible. Use suitably inert tubing, such as polytef, with about

1.6-mm inner diameter and chemically inert flanged-end connections.

9

APPARATUS SUITABILITY

The determination of suitability of a test assembly to perform dissolution

testing must include conformance to the dimensions and tolerances of the

apparatus as given above. In addition, critical test parameters that have to be

monitored periodically during use include volume and temperature of the

Dissolution Medium,

rotation speed

(Apparatus 1

and

Apparatus 2),

dip rate

(Apparatus 3),

and flow rate of medium

(Apparatus 4).

Determine the acceptable performance of the dissolution test assembly

periodically.

The suitability for the individual apparatus is demonstrated by

the

Performance Verification Test

.

Performance Verification Test, Apparatus 1

and

2

—

Individually test 1 tablet of

the

USP Prednisone Tablets RS

and 1 tablet of

USP Salicylic Acid Tablets RS

,

according to the operating conditions specified. The apparatus is suitable if the

results obtained are within the acceptable range stated in the certificate for that

Reference Standard tablet in the apparatus tested.

Performance Verification Test, Apparatus 3

—

Individually test 1 tablet of the

USP Chlorpheniramine Maleate Extended-Release Tablets RS according to

the operating conditions specified. The apparatus is suitable if the results

obtained are within the acceptable range stated in the certificate.

Performance Verification Test, Apparatus 4

—

[To come.]

PROCEDURE

Apparatus 1 and Apparatus 2

IMMEDIATE-RELEASE DOSAGE FORMS

Place the stated volume of the

Dissolution Medium

(±

1%) in the vessel of the

specified apparatus

given in the individual monograph

, assemble the

apparatus, equilibrate the

Dissolution Medium

to 37 ±

0.5

, and remove the

thermometer. Place 1 dosage unit in the apparatus, taking care to exclude air

bubbles from the surface of the dosage unit, and immediately operate the

10