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USP 41 Physical Tests / á705ñ 6457

PROCEDURE
♦Uncoated Tablets♦

Place 1 dosage unit in each of the six tubes of the basket and, if prescribed, add a disk. Operate the apparatus, using ♦water
or♦ the specified medium as the immersion fluid, maintained at 37 ± 2°. At the end of the time limit specified ♦in the mono-
graph,♦ lift the basket from the fluid, and observe the tablets: all of the tablets have disintegrated completely. If 1 or 2 tablets
fail to disintegrate completely, repeat the test on 12 additional tablets. The requirement is met if not fewer than 16 of the total
of 18 tablets tested are disintegrated.

♦Plain-Coated Tablets

Apply the test for Uncoated Tablets, operating the apparatus for the time specified in the individual monograph.

Delayed-Release (Enteric-Coated) Tablets

Place 1 tablet in each of the six tubes of the basket and, if the tablet has a soluble external sugar coating, immerse the bas-
ket in water at room temperature for 5 minutes. Then operate the apparatus using simulated gastric fluid TS maintained at
37 ± 2° as the immersion fluid. After 1 hour of operation in simulated gastric fluid TS, lift the basket from the fluid, and observe
the tablets: the tablets show no evidence of disintegration, cracking, or softening. Operate the apparatus, using simulated in-
testinal fluid TS maintained at 37 ± 2° as the immersion fluid, for the time specified in the monograph. Lift the basket from the
fluid, and observe the tablets: all of the tablets disintegrate completely. If 1 or 2 tablets fail to disintegrate completely, repeat
the test on 12 additional tablets: not fewer than 16 of the total of 18 tablets tested disintegrate completely.

Buccal Tablets

Apply the test for Uncoated Tablets. After 4 hours, lift the basket from the fluid, and observe the tablets: all of the tablets
have disintegrated. If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12 additional tablets: not fewer than 16
of the total of 18 tablets tested disintegrate completely.

Sublingual Tablets

Apply the test for Uncoated Tablets. At the end of the time limit specified in the individual monograph: all of the tablets have
disintegrated. If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12 additional tablets: not fewer than 16 of the
total of 18 tablets tested disintegrate completely.

Hard Gelatin Capsules

Apply the test for Uncoated Tablets. Attach a removable wire cloth, which has a plain square weave with 1.8- to 2.2-mm
mesh apertures and with a wire diameter of 0.60 to 0.655 mm, as described under Basket-Rack Assembly, to the surface of the
upper plate of the basket-rack assembly. Observe the capsules within the time limit specified in the individual monograph: all
of the capsules have disintegrated except for fragments from the capsule shell. If 1 or 2 capsules fail to disintegrate completely,

General Chapters
repeat the test on 12 additional capsules: not fewer than 16 of the total of 18 capsules tested disintegrate completely.

Soft Gelatin Capsules

Proceed as directed under Hard Gelatin Capsules.♦

á705ñ QUALITY ATTRIBUTES OF TABLETS LABELED AS HAVING A


FUNCTIONAL SCORE

PURPOSE

This chapter provides quality attributes for products with approved labeling indicating that the tablets can be split to pro-
duce multiple portions that have an accurate fractional dose (labeled as functionally scored). The label claim of the split por-
tions should be a simple fractional part of the claim for the intact tablet based on the number of scores and the size of the split

Official from August 1, 2018


Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 122.178.52.93 by astrazeneca on Wed Aug 01 06:35:12 EDT 2018
6458 á705ñ / Physical Tests USP 41

portion (e.g., one-half, one-third, or one-quarter). At the time of splitting, the intact tablets should conform to the monograph
specification. With the exception of dose, each split portion from tablets labeled as having a functional score are expected to
conform to the quality attributes of the whole tablets. The split portions resulting from subdividing a functionally scored tablet
should conform to the tests for Splitting Tablets with Functional Scoring and Dissolution or Disintegration given in this chapter.

SCOPE

This chapter applies to tablets labeled as having a functional score and to the split portions that represent any labeled frac-
tion of the whole functionally scored tablet dose. Tablets should be split as part of the test procedure and the storage condi-
tions for the split portions should be defined in the test procedure. For Dissolution or Disintegration testing, analysts should use
only split portions from tablets determined to be acceptable by the Splitting Tablets with Functional Scoring test.

SPLITTING TABLETS WITH FUNCTIONAL SCORING

Test Procedure

1. Take a random sample of 30 intact tablets, and proceed as follows.


2. Accurately weigh each tablet, and record its weight.
3. For each intact tablet, determine the expected weight of the split portions by dividing the whole-tablet weight by the
designated number of split portions indicated on the labeling.
4. Split each tablet by hand (without mechanical assistance) into the designed number of split portions, and weigh each
split portion.
5. For each tablet, determine the percent of the expected weight in each split portion.
An acceptable tablet breaks into the designed number of segments, and each split portion has NLT 75% and NMT 125% of
the expected weight of the split tablet portion. [NOTE—Set aside split tablet portions derived from acceptable tablets for subse-
quent testing for dissolution or disintegration.]
Acceptance criteria: NLT 28 of the 30 tablets are acceptable.

DISSOLUTION

Use split portions from tablets that are acceptable according to the Splitting Tablets with Functional Scoring test.

Immediate-Release Tablets

Dissolution for immediate-release tablets is performed at the S2 stage (see Dissolution á711ñ). Test 12 split tablet portions ac-
cording to the specified Medium, Apparatus, Times, and Analysis. The average of the 12 results is NLT Q, and no result is less
than Q – 15%.

Extended-Release Tablets

Perform dissolution testing of split tablet portions from extended-release tablets by one of the two alternative procedures.
The procedure to be used is specified in the monograph.
General Chapters

Procedure 1 (Procedure for Extended-Release Dosage Forms, Dissolution á711ñ): Individually test 12 split tablet portions and 12
intact tablets.
Medium, Apparatus, and Analysis: As given in the monograph following the appropriate test number found on the label-
ing. Dissolution profile test time points are determined as follows. From the appropriate dissolution test in the monograph, use
the time points given. At a minimum, use three time points with no more than one time point where the results exceed 85%
dissolved.
Calculate the similarity factor (f2) for the intact-tablet results and the split-tablet portion results:

Rt = cumulative percentage of the labeled drug dissolved at each of the selected n time points of the intact tablets
Tt = cumulative percentage of the labeled drug dissolved at each of the selected n time points of the split tablet portions
Acceptance criteria: The calculated f2 is NLT 50 (acceptable range: 50–100).
Procedure 2 (Procedure for Extended-Release Dosage Forms, Dissolution á711ñ): Use a split-tablet portion as the dosage unit.
Individually test 12 dosage units.

Official from August 1, 2018


Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 122.178.52.93 by astrazeneca on Wed Aug 01 06:35:12 EDT 2018
USP 41 Physical Tests / á711ñ 6459

Medium, Apparatus, Times, and Analysis: As given in the monograph following the appropriate test number found on the
labeling.
Acceptance criteria: The percentages of the labeled amount released at the times specified conform to the L2 level criteria
of Acceptance Table 2 in á711ñ.

DISINTEGRATION

Disintegration testing is necessary only when used as a surrogate for dissolution testing as specified in the monograph. Fol-
low the procedure using split portions from tablets that are acceptable according to the Splitting Tablets with Functional Scoring
test as the dosage unit (see Disintegration á701ñ).

á711ñ DISSOLUTION

General chapter Dissolution á711ñ is being harmonized with the corresponding texts of the European Pharmacopoeia and/or
the Japanese Pharmacopoeia. These pharmacopeias have undertaken to not 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 (♦♦) to specify this fact.
This test is provided to determine compliance with the dissolution requirements ♦where stated in the individual monograph♦
for dosage forms 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 designs described herein, use the one specified in the individual monograph. Where the
label states that an article is enteric coated and a dissolution or disintegration test does not specifically state that it is to be
applied to delayed-release articles and is included in the individual monograph, the procedure and interpretation given for
Delayed-Release Dosage Forms are applied, unless otherwise specified in the individual monograph.

FOR DOSAGE FORMS CONTAINING OR COATED WITH GELATIN

If the dosage form containing gelatin does not meet the criteria in the appropriate Acceptance Table (see Interpretation, Im-
mediate-Release Dosage Forms, Extended-Release Dosage Forms, or Delayed-Release Dosage Forms) because of evidence of the
presence of cross-linking, the dissolution procedure should be repeated with the addition of enzymes to the medium, as de-
scribed below, and the dissolution results should be evaluated starting at the first stage of the appropriate Acceptance Table. It
is not necessary to continue testing through the last stage (up to 24 units) when criteria are not met during the first stage
testing, and evidence of cross-linking is observed.
Gelatin, in the presence of certain compounds and/or in certain storage conditions, including but not restricted to high hu-
midity and temperature, may present cross-linking. A pellicle may form on the external and/or internal surface of the gelatin
capsule shell or on the dosage form that prevents the drug from being released during dissolution testing (see more informa-
tion in Capsules—Dissolution Testing and Related Quality Attributes á1094ñ).
[NOTE—All references to a chapter above á1000ñ are for information purposes only, for use as a helpful resource. These chap-
ters are not mandatory unless explicitly called out for this application.]

General Chapters
Dissolution Medium with pH £4.0

Enzyme: Pepsin, activity determined by the procedure in purified pepsin, in the Reagent Specifications section
Amount: A quantity of pepsin that results in an activity of NMT 750,000 Units/L of dissolution medium

Dissolution Medium with pH >4.0 and <6.8

Enzyme: Papain, activity determined by the Assay test in the monograph for Papain; or bromelain, activity determined by
the procedure in bromelain, in the Reagent Specifications section
Amount: A quantity of papain that results in an activity of NMT 550,000 Units/L of dissolution medium, or a quantity of
bromelain that results in an activity of NMT 30 gelatin-digesting units (GDU)/L of dissolution medium

Dissolution Medium with pH ³6.8

Enzyme: Pancreatin, protease activity determined by the procedure in Assay for protease activity (Casein digestive power) in
the monograph for Pancreatin
Amount: A quantity of pancreatin that results in a protease activity of NMT 2000 Units/L of dissolution medium

Official from August 1, 2018


Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.