Basket-Rack Assembly— The basket-rack assembly consists of three open-ended transparent tubes, each 7.95- ± 0.05-cm long and having an inside diameter of approximately 33.3-mm and a wall approximately 2.4 mm thick; the tubes are held in a vertical position by two plastic plates, each about 9.7 cm in diameter and 9.5 mm in thickness, with three holes, each about 39 mm in diameter, equidistant from the center of the plate and equally spaced from one another. Attached to the under surface of the lower plate is 10-mesh No. 23 (0.025-inch) W. and M. gauge woven stainless-steel wire cloth having a plain square weave. The parts of the apparatus are assembled and rigidly held by means of three bolts passing through the two plastic plates. A suitable means is provided to suspend the basket-rack assembly from the raising and lowering device using a point on its axis.

Disks— Each tube is provided with a perforated cylindrical disk 15.3- ± 0.15-mm thick and 31.4 ± 0.13 mm in diameter. The disk is made of a suitable, transparent plastic material having a specific gravity of between 1.18 and 1.20. Seven 3.2-mm holes extend between the ends of the cylinder, one of the holes being through the cylinder axis and the others parallel with it equally spaced on a 6-mm radius from it. All surfaces of the disk are smooth.

VITAMIN-MINERAL DOSAGE FORMS

Uncoated Tablets and Film-Coated Tablets— Place 1 tablet in each of the tubes of the basket, add a disk to each tube, and operate the apparatus, using water maintained at 37 ± 2 as the immersion fluid. At the end of 30 minutes, 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.

Plain Coated Tablets (Other Than Film-Coated Tablets)— Place 1 tablet in each of the tubes of the basket and, if the tablet has a soluble external coating, immerse the basket in water at room temperature for 5 minutes. Then add a disk to each tube, and operate the apparatus, using water maintained at 37 ± 2 as the immersion fluid. After 45 minutes of operation in water, 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: not fewer than 16 of the total of 18 tablets tested disintegrate completely.

Hard Gelatin Capsules— Apply the test for Uncoated Tablets, using 0.05 M acetate buffer, prepared by mixing 2.99 g of sodium acetate trihydrate and 1.66 mL of glacial acetic acid with water to obtain 1000 mL of solution having a pH of 4.50 ± 0.05, maintained at 37 ± 2 as the immersion fluid. At the end of 45 minutes, lift the basket from the fluid, and observe the capsules: all of the capsules disintegrate except for fragments from the capsule shell. If 1 or 2 capsules fail to disintegrate completely, 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.

BOTANICAL DOSAGE FORMS

Uncoated Tablets and Film-Coated Tablets— [NOTE—Omit the use of disks unless otherwise specified in the individual monograph.] Place 1 tablet in each of the tubes of the basket, and operate the apparatus, using water maintained at 37 ± 2 as the immersion fluid. At the end of 20 minutes, 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.

Plain Coated Tablets (other than Film-Coated Tablets)— [NOTE—Omit the use of disks, unless otherwise specified in the individual monograph.] Place 1 tablet in each of the tubes of the basket and, if the tablet has a soluble external coating, immerse the basket in water at room temperature for 5 minutes. Operate the apparatus using water maintained at 37 ± 2 as the immersion fluid. After 20 minutes of operation in water, lift the basket from the fluid, and observe the tablets: all of the tablets have disintegrated completely. If 1 or 2 of the 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.

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 coating, immerse the basket 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 intestinal 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.

Hard Gelatin Capsules— Apply the test for Uncoated Tablets, using 0.05 M acetate buffer, prepared by mixing 2.99 g of sodium acetate trihydrate and 1.66 mL of glacial acetic acid with water to obtain 1000 mL of solution having a pH of 4.50 ± 0.05, maintained at 37 ± 2 as the immersion fluid. At the end of 20 minutes, lift the basket from the fluid, and observe the capsules: all of the capsules disintegrate except for fragments from the capsule shell. If 1 or 2 capsules fail to disintegrate completely, 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.

This test is provided to determine compliance with the dissolution requirements where stated in the individual class monographs for a tablet or capsule dosage form, except where the label states that the tablets are to be chewed. It does not apply to tablets or capsules designed to release vitamin or mineral content over a delayed or extended period of time. Soft gelatin capsule preparations of dietary supplements meet the requirements for Disintegration.

All dietary supplements belonging to USP Classes II to VI, prepared as tablets or capsules, are subject to the dissolution test and criteria described in this chapter for folic acid (if present) and for index vitamins and index minerals. This test is also required if the product labeling includes a health claim concerning the relationship between folate deficiency and the risk of neural tube defects. The accompanying table lists the dissolution requirements for the individual USP classes of dietary supplements. Class I dietary supplements are combinations of oil-soluble vitamins, which are exempt from dissolution requirements; hence, dissolution requirements do not apply to the oil-soluble vitamins contained in formulations belonging to Class IV or Class V.

Dietary Supplements—Vitamin–Mineral
Dosage Forms

Unless otherwise stated in the individual monograph, test 6 dosage units for dissolution as directed under Dissolution 711.

DISSOLUTION CONDITIONS FOR FOLIC ACID

NOTE—Perform this test under subdued light.

Medium: water; 900 mL. If the units tested do not meet the requirements for dissolution in water, test 6 additional dosage units for dissolution in a medium of 900 mL of 0.05 M pH 6.0 citrate buffer solution, prepared by mixing 9.5 mL of 0.1 M citric acid monohydrate and 40.5 mL of 0.1 M sodium citrate dihydrate in a 100-mL volumetric flask, diluting with water to volume, mixing, and adjusting to a pH of 6.0 by using either 0.1 M hydrochloric acid or 0.1 M sodium hydroxide solution.

Apparatus 1: 100 rpm, for capsules.

Apparatus 2: 75 rpm, for tablets.

Time: 1 hour.

DISSOLUTION CONDITIONS FOR INDEX VITAMINS and INDEX MINERALS

Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 1: 100 rpm, for capsules.

Apparatus 2: 75 rpm, for tablets.

Time: 1 hour.

Medium: 0.1 N hydrochloric acid; 1800 mL.

Apparatus 1: 100 rpm, for capsules.

Apparatus 2: 75 rpm, for tablets.

Time: 1 hour.

SELECTION OF INDEX VITAMINS and INDEX ELEMENTS

PROCEDURES

Folic Acid— Determine the amount of C19H19N7O6 dissolved by employing the procedure set forth in the Assay for folic acid under Oil- and Water-Soluble Vitamins with Minerals Tablets, in comparison with a Standard solution having a known concentration of USP Folic Acid RS in the same medium.

Niacin or Niacinamide, Pyridoxine, Riboflavin, and Thiamine— Determine the amount of the designated index vitamin dissolved by employing the procedure set forth in the Assay for niacin or niacinamide, pyridoxine, riboflavin, and thiamine under Water-Soluble Vitamins Tablets.

Ascorbic Acid— Determine the amount of C6H8O6 dissolved by adding 10 mL of 1.0 N sulfuric acid and 3 mL of starch TS to 100.0 mL of test solution, and titrating immediately with 0.01 N iodine VS. Perform a blank determination, and make any necessary correction.

Iron, Calcium, Magnesium, and Zinc— Determine the amount of the designated index element dissolved by employing the procedure set forth in the appropriate Assay under Minerals Capsules.

TOLERANCES

This test is provided to determine compliance with the dissolution requirements where stated in the individual monograph for a tablet or capsule dosage form. See Dissolution 711 for description of apparatus used, Apparatus Suitability Test, and other related information. Of the types of apparatus described in 711, use the one specified in the individual monograph. Where the label states that an article is enteric-coated, and a dissolution or disintegration test that does not specifically state that it is to be applied to enteric-coated articles is included in the individual monograph, the test for Delayed-Release Articles under Drug Release 724 is applied, unless otherwise specified in the individual monograph. Compliance with dissolution requirements is determined by testing 6 dosage units individually, or testing 2 or more counted number of dosage units in each vessel, and measuring the dissolution of one or more index/marker compound(s) or the extract specified in the individual monograph. This nonspecific dissolution is intended to be diagnostic of known technological problems that may arise due to coatings, lubricants, disintegrants, and other substances inherent in the manufacturing process. Further, this dissolution measurement allows an assessment of the extent of decomposition of the extract to polymeric or other nondissoluble compounds that may have been produced by excessive drying or other manipulations involved in the manufacture of botanical extracts. The operative assumption inherent in this procedure is that if the index or marker compound(s) or the extract is demonstrated to have dissolved within the time frame and under conditions specified, the dosage form does not suffer from any of the above formulation or manufacturing related problems.

PROCEDURES

INTERPRETATION

Pooled Sample— Unless otherwise specified in the individual monograph, the requirements are met if the quantities of the index or marker compound(s) or the extract dissolved from the pooled sample conform to the accompanying acceptance table. The quantity, Q, is the amount of dissolved index or marker compound(s) or the extract specified in the individual monograph, expressed as a percentage of the labeled content. The 5%, 15%, and 25% values in the acceptance table are percentages of the labeled content so that these values and Q are in the same terms.