§ 331.26 - Acid neutralizing capacity test.

(a) pH meter. Standardize the pH meter at pH 4.0 with the standardizing buffer and check for proper operation at pH 1 with 0.1 N HCl.

(b) Dosage form testing—(1) Liquid sample. Place an accurately weighed (calculate density) and well mixed amount of product equivalent to the minimum labeled dosage (e.g., 5 ml., etc.) into a 250 ml. beaker. Add sufficient water to obtain a total volume of about 70 ml. and mix on the magnetic stirrer at 300±30 r.p.m. for about one minute. Analyze the sample according to the procedure set forth in § 331.26.

(2) Chewable and non-chewable tablet sample. Place an accurately weighed amount of a tablet composite equivalent to the minimum labeled dosage into a 250 ml. beaker. (The composite shall be prepared by determining the average weight of not less than 20 tablets and then comminuting the tablets sufficiently to pass through a number 20 U.S. standard mesh sieve and held by a number 100 U.S. standard mesh sieve. Mix the sieved material to obtain a uniform sample.) If wetting is desired, add not more than 5 ml. of 95 percent ethanol and mix to wet the sample thoroughly (ethanol may effect the acid neutralizing capacity). Add water to a volume of 70 ml. and mix on magnetic stirrer at 300±30 r.p.m. for about one minute. (Capsules should be tested in the same manner using the sieved capsule powder as the sample.) Analyze the sample according to the procedure set forth in § 331.26.

(3) Effervescent sample. Place an amount equivalent to the minimum labeled dosage into a 250 ml. beaker. Add 10 ml. water and swirl the beaker gently while allowing the reaction to subside. Add another 10 ml. of water and swirl the beaker gently. Wash down the walls of the beaker with 50 ml. of water and mix on magnetic stirrer at 300±30 r.p.m. for about one minute. Analyze the sample according to the procedure set forth in § 331.26.

(4) Sample and test procedure for chewing gum with antacid in coating. Assay six pieces of gum individually in the following manner.

(i) Place one piece of gum in a 250 ml. beaker and add 50 ml. of water.

(ii) Pipette in 30.0 ml. of 1.0 N HCl and stir on magnetic stirrer at 300±30 r.p.m.

(iii) Stir for exactly 10 minutes after addition of acid.

(iv) Stop the stirrer and remove the gum using a long needle or similar utensil.

(v) Rinse the long needle or utensil and the gum with 20 ml. of water into the sample beaker.

(vi) Stir for exactly 5 additional minutes.

(vii) Begin titrating immediately and in a period of time not to exceed 5 minutes titrate the excess 1.0 N HCl with 0.5 N NaOH to stable pH of 3.5.

(viii) Check sample solution 10 to 15 seconds after obtaining pH 3.5 to determine that the pH is stable.

(ix) Average the results of the six individual assays and calculate the total mEq. based on the minimum labeled dosage as follows:

(c) Acid neutralizing capacity test procedure (except chewing gum). (1) Pipette 30.0 ml. of 1.0 N HCl into the sample solution while stirring on the magnetic stirrer at 300±30 r.p.m.

(2) Stir for exactly 15 minutes after addition of acid.

(3) Begin titrating immediately and in a period not to exceed an additional 5 minutes titrate the excess 1.0 N HCl with 0.5 N NaOH to stable pH of 3.5.

(4) Check the sample solution 10 to 15 seconds after obtaining pH 3.5 to make sure the pH is stable.

(5) Calculate the number of mEq. of acid neutralized by the sample as follows:

Use appropriate factors, i.e., density, average tablet weight, etc., to calculate the total mEq. of acid neutralized per minimum labeled dosage.