(c) Resolution. The resolution (R) between the clavulanic acid and amoxicillin peaks is satisfactory if it is not less than 3.5. (d) Coefficient of variation. The coefficient of variation (SR in percent) of five replicate injections is satisfactory if it is not more than 2.0 percent. If the system suitability requirements have been met, then proceed as described in § 436.351(b) of this chapter. (iv) Calculations. Calculate the milligrams of amoxicillin or clavulanic acid content per tablet as follows: A. Response of the amoxicillin or clavulanic acid peak in the chromatogram of the sample (at a retention time equal to that observed for the standard); A, Response of the amoxicillin or clavulanic acid peak in the chromatogram of the amoxicillin or clavulanic acid working standard; C, Concentration of standards in milligrams of amoxicillin or clavulanic acid per milliliter of the standard solution; V=Volume of sample solution (milliliters); and N=Number of tablets taken for assay. (2) Moisture. Proceed as directed in § 436.201 of this chapter. (3) Dissolution. Proceed as directed in § 436.215 of this chapter. Dissolution rate is determined by dissolution of the amoxicillin component using the highperformance liquid chromatographic assay described in this section. [50 FR 42933, Oct. 25, 1985; 50 FR 47367, Nov. 17, 1985, as amended at 55 FR 11582, Mar. 29, 1990] § 440.105 Ampicillin oral dosage forms. § 440.105a Ampicillin tablets. (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Ampicillin tablets are composed of ampicillin with one or more suitable and harmless diluents and lubricants. Each tablet contains 250 or 500 milligrams of ampicillin. Its potency is satisfactory if it is not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. Its loss on drying is not more than 4 percent. The tablets disintegrate within 15 minutes. The ampicillin used conforms to the standards prescribed by § 440.5(a)(1). (2) Labeling. It shall be labeled in accordance with the requirements of § 432.5 of this chapter. (3) Requests for certification; samples. In addition to complying with the requirements of § 431.1 of this chapter, each such request shall contain: (i) Results of tests and assays on: (a) The ampicillin used in making the batch for potency, loss on drying, pH, ampicillin content, concordance, crystallinity, and identity. (b) The batch for potency, loss on drying, and disintegration time. (ii) Samples required: (a) The ampicillin used in making the batch: 10 packages, each containing approximately 300 milligrams. (b) The batch: A minimum of 36 tablets. (b) Tests and methods of assay—(1) Potency. Use either of the following methods; however, the results obtained from the microbiological agar diffusion assay shall be conclusive. (i) Microbiological agar diffusion assay. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Place a representative number of tablets into a high-speed glass blender jar with sufficient 0.1M potassium phosphate buffer, pH 8.0 (solution 3), to give a stock solution of convenient concentration. Blend for 3 to 5 minutes. Remove an aliquot and further dilute with solution 3 to the reference concentration of 0.1 microgram of ampicillin per milliliter (estimated). (ii) Iodometric assay. Proceed as directed in §436.204 of this chapter, except in paragraph (d) of that section, add 3 drops of 1.2N hydrochloric acid to both the sample and working standard solutions after the addition of 0.01N iodine solution. Prepare the sample as follows: Place a representative number of tablets in a high-speed glass blender jar and add sufficient distilled water to give a convenient concentration. Blend for 3 to 5 minutes. Further dilute an aliquot with distilled water to the prescribed concentration. (2) Loss on drying. Proceed as directed in § 436.200(a) of this chapter. (3) Disintegration time. Proceed as directed in § 436.212 of this chapter, using the procedure described in paragraph (e)(1) of that section. [39 FR 18976, May 30, 1974, as amended at 49 FR 3458, Jan. 27, 1984; 50 FR 19919, May 13, 1985] § 440.105b Ampicillin chewable tablets. (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Each ampicillin chewable tablet contains 125 milligrams or 250 milligrams of ampicillin with suitable binders, lubricants, flavorings, and colorings. Its potency is satisfactory if it is not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. Its loss on drying is not more than 3 percent. The ampicillin used conforms to the standards prescribed by §440.5(a)(1). (2) Labeling. In addition to the labeling requirements prescribed by § 432.5 of this chapter, this drug shall be labeled "ampicillin tablets". (3) Requests for certification; samples. In addition to complying with the requirements of §431.1 of this chapter, each such request shall contain: (i) The results of tests and assays on: (a) The ampicillin used in making the batch for potency, loss on drying, pH, ampicillin content, concordance, crystallinity, and identity. (b) The batch for potency and loss on drying. (ii) Samples required: (a) The ampicillin used in making the batch: 10 packages, each containing approximately 300 milligrams. (b) The batch: A minimum of 30 tablets. (b) Tests and methods of assay—(1) Potency. Use either of the following methods; however, the results obtained from the microbiological agar diffusion assay shall be conclusive. (i) Microbiological agar diffusion assay. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Place a representative number of tablets into a high-speed glass blender jar with sufficient 0.1M potassium phosphate buffer, pH 8.0 (solution 3), to give a stock solution of convenient concentration. Blend for 3 to 5 minutes. Remove an aliquot and fur ther dilute with solution 3 to the reference concentration of 0.1 microgram of ampicillin per milliliter (estimated). (ii) Iodometric assay. Proceed as directed in § 436.204 of this chapter, except in paragraph (d) of that section, add 3 drops of 1.2N hydrochloric acid to both the sample and working standard solutions after the addition of 0.01N iodine solution. Prepare the sample as follows: Blend a representative number of tablets in a high-speed blender with sufficient distilled water to give a stock solution of convenient concentration. Blend for 3 to 5 minutes. Further dilute an aliquot of the stock solution with distilled water to the prescribed concentration. (2) Loss on drying. Proceed as directed in § 436.200(a) of this chapter. [39 FR 18976, May 30, 1974, as amended at 43 FR 9800, Mar. 10, 1978; 49 FR 3458, Jan. 27, 1984; 50 FR 19919, May 13, 1985] $440.105c Ampicillin capsules. (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Ampicillin capsules are composed of ampicillin with or without one or more buffer substances, diluents, binders, lubricants, vegetable oils, colorings, and flavorings, enclosed in a gelatin capsule. Each capsule contains 125 milligrams, 250 milligrams, or 500 milligrams of ampicillin. Its potency is satisfactory if it is not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. The loss on drying is not more than 4.0 percent. The ampicillin used conforms to the standards prescribed by § 440.5(a)(1). (2) Labeling. It shall be labeled in accordance with the requirements of § 432.5 of this chapter. (3) Requests for certification; samples. In addition to complying with the requirements of § 431.1 of this chapter, each such request shall contain: (i) Results of tests and assays on: (a) The ampicillin used in making the batch for potency, loss on drying, pH, ampicillin content, concordance, crystallinity, and identity. (b) The batch for potency and loss on drying. (ii) Samples required: (a) The ampicillin used in making the batch: 10 packages, each containing approximately 300 milligrams. (b) The batch: A minimum of 30 capsules. (b) Tests and methods of assay—(1) Potency. Assay for potency by either of the following methods; however, the results obtained from the microbiological agar diffusion assay shall be conclusive. (i) Microbiological agar diffusion assay. Proceed as directed in §436.105 of this chapter, preparing the sample for assay as follows: Place a representative number of capsules into a high-speed glass blender jar with sufficient 0.1M potassium phosphate buffer, pH 8.0 (solution 3), to give a convenient concentration. Blend for 3 to 5 minutes. Remove an aliquot and further dilute with solution 3 to the reference concentration of 0.1 microgram of ampicillin per milliliter (estimated). (ii) Iodometric assay. Proceed as directed in § 436.204 of this chapter, except in paragraph (d) of that section, add 3 drops of 1.2N hydrochloric acid to both the sample and working standard solutions after the addition of 0.01N iodine solution. Prepare the sample as follows: Place the contents of a representative number of capsules into a high-speed glass blender jar and add sufficient distilled water to give a convenient concentration. Blend for 3 to 5 minutes. Filter through Whatman No. 2 filter paper. Further dilute an aliquot of the filtrate with distilled water to the prescribed concentration. (2) Loss on drying. Proceed as directed in § 436.200(a) of this chapter. [39 FR 18976, May 30, 1974, as amended at 49 FR 3458, Jan. 27, 1984; 50 FR 19919, May 13, 1985] § 440.105d Ampicillin for oral suspension. (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Ampicillin for oral suspension is a mixture of ampicillin with one or more suitable and harmless colorings, flavorings, buffer substances, sweetening ingredients, and preservatives. When reconstituted as directed in the labeling, it contains either 25 milligrams, 50 milligrams, or 100 milligrams of ampicillin per milliliter. Its potency is satisfactory if it is not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. Its moisture content is not more than 2.5 percent. When reconstituted as directed in the labeling, its pH is not less than 5.0 and not more than 7.5. The ampicillin used conforms to the standards prescribed by § 440.5(a)(1). (2) Labeling. It shall be labeled in accordance with the requirements of § 432.5 of this chapter. (3) Requests for certification; samples. In addition to complying with the requirements of § 431.1 of this chapter, each such request shall contain: (i) Results of tests and assays on: (a) The ampicillin used in making the batch for potency, loss on drying, pH, ampicillin content, concordance, crystallinity, and identity. (b) The batch for potency, moisture, and pH. (ii) Samples required: (a) The ampicillin used in making the batch: 10 packages, each containing approximately 300 milligrams. (b) The batch: A minimum of 6 immediate containers. (b) Tests and methods of assay-(1) Potency. Assay for potency by either of the following methods; however, the results obtained from the microbiological agar diffusion assay shall be conclusive. (i) Microbiological agar diffusion assay. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Reconstitute the drug as directed in the labeling. Place an accurately measured representative portion of the sample into a suitable volumetric flask and dilute to volume with 0.1M potassium phosphate buffer, pH 8.0 (solution 3), to give a convenient concentration. Mix well. Further dilute an aliquot with solution 3 to the reference concentration of 0.1 microgram of ampicillin per milliliter (estimated). (ii) Iodometric assay. Proceed as directed in § 436.204 of this chapter, except in paragraph (d) of that section, add 3 drops of 1.2N hydrochloric acid to both the sample and working standard solutions after the addition of 0.01N iodine solution. Prepare the sample as 179-070 0-98--18 follows: Reconstitute the drug as directed in the labeling. Place an accurately measured aliquot (usually a single dose) into an appropriately sized volumetric flask and dilute to volume with distilled water. Mix well. Further dilute with distilled water to the prescribed concentration. (2) Moisture. Proceed as directed in § 436.201 of this chapter. (3) pH. Proceed as directed in § 436.202 of this chapter, using the drug reconstituted as directed in the labeling. [39 FR 18976, May 30, 1974, as amended at 49 FR 3458, Jan. 27, 1984; 50 FR 19919, May 13, 1985] (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Ampicillin trihydrate chewable tablets are composed of ampicillin trihydrate with or without one or more suitable diluents, lubricants, preservatives, and flavorings. Each tablet contains ampicillin trihydrate equivalent to 125 or 250 milligrams of ampicillin. Its potency is satisfactory if it contains not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. Its moisture content is not more than 5.0 percent. The ampicillin trihydrate used conforms to the standards prescribed by § 440.7(a)(1). (2) Labeling. In addition to the labeling requirements prescribed by § 432.5 of this chapter, this drug shall be labeled "ampicillin tablets." (3) Requests for certification; samples. In addition to complying with the requirements of § 431.1 of this chapter, each such request shall contain: (i) Results of tests and assays on: (a) The ampicillin trihydrate used in making the batch for potency, loss on drying, pH, ampicillin content, concordance, crystallinity, and identity. (b) The batch for potency and moisture. (ii) Samples required: (a) The ampicillin trihydrate used in making the batch: 10 packages, each containing approximately 300 milligrams. (b) The batch: A minimum of 30 tablets. (b) Tests and methods of assay—(1) Potency. Use either of the following methods; however, the results obtained from the microbiological agar diffusion assay shall be conclusive. (i) Microbiological agar diffusion assay. Proceed as directed in § 436.105 of this chapter, preparing the sample for assay as follows: Place a representative number of tablets into a high-speed glass blender jar with sufficient 0.1M potassium phosphate buffer, pH 8.0 (solution 3), to give a stock solution of convenient concentration. Blend for 3 to 5 minutes. Remove an aliquot and further dilute with solution 3 to the reference concentration of 0.1 microgram of ampicillin per milliliter (estimated). (ii) Iodometric assay. Proceed as directed in §436.204 of this chapter, except in paragraph (d) of that section, add 3 drops of 1.2N hydrochloric acid to both the sample and working standard solutions after the addition of 0.01N iodine solution. Prepare the sample as follows: Place a representative number of tablets into a high-speed glass blender jar containing sufficient distilled water to give a convenient concentration. Blend for 5 minutes. Further dilute with distilled water to the prescribed concentration. (2) Moisture. Proceed as directed in § 436.201 of this chapter. [39 FR 18976, May 30, 1974, as amended at 49 FR 3459, Jan. 27, 1984; 50 FR 19919, May 13, 1985] § 440.107b Ampicillin trihydrate capsules. (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Ampicillin trihydrate capsules are composed of ampicillin trihydrate with or without one or more buffer substances, diluents, binders, lubricants, vegetable oils, colorings, and flavorings enclosed in a gelatin capsule. Each capsule contains ampicillin trihydrate equivalent to 250 milligrams or 500 milligrams of ampicillin. Its potency is satisfactory if it contains not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. Its loss on drying is not less than 10 percent and not more than 15 percent. The ampicillin trihydrate used conforms to the standards prescribed by § 440.7(a)(1). (2) Labeling. In addition to the labeling requirements prescribed by §432.5 of this chapter, this drug shall be labeled "ampicillin capsules”. (3) Requests for certification; samples. In addition to complying with the requirements of §431.1 of this chapter, each such request shall contain: (i) Results of tests and assays on: (a) The ampicillin trihydrate used in making the batch for potency, loss on drying, pH, ampicillin content, concordance, crystallinity, and identity. (b) The batch for potency and loss on drying. (ii) Samples required: (a) The ampicillin trihydrate used in making the batch: 10 packages, each containing approximately 300 milligrams. (b) The batch: A minimum of 30 capsules. (b) Tests and methods of assay—(1) Potency. Assay for potency by either of the following methods; however, the results obtained from the microbiological agar diffusion assay shall be conclusive. (i) Microbiological agar diffusion assay. Proceed as directed in §436.105 of this chapter, preparing the sample for assay as follows: Place a representative number of capsules into a high-speed glass blender jar with sufficient 0.1M potassium phosphate buffer, pH 8.0 (solution 3), to give a convenient concentration. Blend for 3 to 5 minutes. Remove an aliquot and further dilute with solution 3 to the reference concentration of 0.1 microgram of ampicillin per milliliter (estimated). (ii) Iodometric assay. Proceed as directed in § 436.204 of this chapter, except in paragraph (d) of that section, add 3 drops of 1.2N hydrochloric acid to both the sample and working standard solutions after the addition of 0.01N iodine solution. Prepare the sample as follows: Place the contents of a representative number of capsules into a high-speed glass blender jar and add sufficient distilled water to give a con venient concentration. Blend for 3 to 5 minutes. Filter through Whatman No. 2 filter paper. Further dilute an aliquot of the filtrate with distilled water to the prescribed concentration. (2) Loss on drying. Proceed as directed in § 436.200(a) of this chapter. [39 FR 18976, May 30, 1974, as amended at 49 FR 3459, Jan. 27, 1984; 50 FR 19919, May 13, 1985] § 440.107c Ampicillin trihydrate for oral suspension. (a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Ampicillin trihydrate for oral suspension is a mixture of ampicillin trihydrate with one or more suitable and harmless colorings, flavorings, buffers, sweetening ingredients, and preservatives. When reconstituted as directed in the labeling, it contains ampicillin trihydrate equivalent to either 25, 50, or 100 milligrams of ampicillin per milliliter. Its potency is satisfactory if it is not less than 90 percent and not more than 120 percent of the number of milligrams of ampicillin that it is represented to contain. Its moisture content is: (i) Not more than 2.5 percent if it contains sugar and is intended to contain the equivalent of 25 or 50 milligrams of ampicillin per milliliter when reconstituted as directed in the labeling; or (ii) Not more than 5 percent if it contains sugar and is intended to contain the equivalent of 100 milligrams of ampicillin per milliliter when reconstituted as directed in the labeling; or Its pH, when reconstituted as directed in the labeling, is not less than 5.0 and is not more than 7.5. The ampicillin trihydrate used conforms to the standards prescribed by § 440.7(a)(1). (2) Labeling. In addition to the labeling requirements prescribed by §432.5 of this chapter, this drug shall be labeled "ampicillin for oral suspension." (3) Requests for certification; samples. In addition to complying with the requirements of §431.1 of this chapter, each such request shall contain: (i) Results of tests and assays on: (a) The ampicillin trihydrate used in making the batch for potency, loss on |