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(ii) Calculate the percent of labeled amount of erythromycin released in 60 minutes as follows:

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440.155d Penicillin G benzathine tablets. 440.171 Penicillin V oral dosage forms. 440.171a Penicillin V capsules.

440.171b Penicillin V for oral suspension. 440.171c Penicillin V tablets.

440.173 Penicillin V potassium oral dosage forms.

440.173a Penicillin V potassium capsules. 440.173b Penicillin V potassium chewable tablets.

440.173c Penicillin V potassium tablets. 440.173d Penicillin V potassium for oral solution.

440.180 Penicillin G potassium oral dosage forms.

440.180a Penicillin G potassium tablets. 440.180c Penicillin G potassium capsules. 440.180f Penicillin G potassium for oral solution.

440.180g Penicillin G potassium tablets for

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440.249b Oxacillin sodium injection.

440.255 Penicillin G benzathine injectable dosage forms.

440.255b Sterile penicillin G benzathine suspension.

440.255c Sterile penicillin G benzathine-penicillin G procaine suspension.

440.255d Sterile penicillin G benzathine for suspension.

440.274 Penicillin G procaine injectable dosage forms.

440.274a Sterile penicillin G procaine with aluminum stearate suspension.

440.274b Sterile penicillin G procaine suspension.

440.274c Sterile penicillin G procaine for suspension.

440.280 Penicillin G potassium injectable dosage forms.

440.280a Sterile penicillin G potassium. 440.280b Penicillin G potassium for injection.

440.280c Penicillin G potassium injection. 440.281 Penicillin G sodium injectable dosage forms.

440.281a Sterile penicillin G sodium. 440.281b Penicillin G sodium for injection. 440.283 Sterile piperacillin sodium.

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3,3-dimethyl-7-oxo-6-[[[[(2-oxo-1

imidazolidinyl)carbonyl]

amino]phenylac-etyl]amino]-[2S[2α,5a,6ẞ(S*)]]-. It is so purified and dried that:

(i) If the azlocillin sodium is not packaged for dispensing, its azlocillin content is not less than 859 micrograms and not more than 1,000 micrograms of azlocillin per milligram on an anhydrous basis. If the azlocillin sodium is packaged for dispensing, its azlocillin content is not less than 859 micrograms and not more than 1,000 micrograms of azlocillin per milligram on an anhydrous basis and also, each container contains not less than 90 percent and not more than 115 percent of the number of milligrams of azlocillin that it is represented to contain.

(ii) It is sterile.

(iii) It is nonpyrogenic.

(iv) Its moisture content is not more than 2.5 percent.

(v) Its pH in an aqueous solution containing 100 milligrams of azlocillin per milliliter is not less than 6.0 and not more than 8.0.

(vi) Its specific rotation in an aqueous solution containing 10 milligrams of azlocillin per milliliter is +170° to + 200°.

(vii) It gives a positive identity test for azlocillin.

(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 the batch for potency, sterility, pyrogens, moisture, pH, specific rotation, and identity.

(ii) Samples, if required by the Director, Center for Drug Evaluation and Research:

(a) If it is packaged for repacking or for use in the manufacture of another drug:

(1) For all tests except sterility: 10 packages, each containing approximately 300 milligrams; and 5 packages, each containing approximately 1 gram.

(2) For sterility testing: 20 packages, each containing approximately 300 milligrams.

(b) If it is packaged for dispensing:

(1) For all tests except sterility: A minimum of 15 immediate containers.

(2) For sterility testing: 20 immediate containers, collected at regular intervals throughout each filling operation.

(b) Tests and methods of assay—(1) Potency. Proceed as directed

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§ 442.40(b)(1)(ii) of this chapter, except: (i) Dilute Brij 35 solution. In lieu of the hydroxylamine hydrochloride solution described in § 442.40(b)(1)(ii)(b)(1) of this chapter, use dilute Brij 35 solution in the reference channel. Prepare dilute Brij 35 solution as follows: Place 1 milliliter of Brij 35, 30 percent solution, into a 1-liter volumetric flask containing 900 milliliters of distilled water. Swirl gently and dilute to volume slowly with distilled water. Mix well.

(ii) Buffer. In lieu of the buffer described in § 442.40(b)(1)(ii)(b)(2) of this chapter, use the buffer prepared as follows: Dissolve 200 grams of primary standard tris (hydroxymethyl) aminomethane in sufficient distilled water to make 1 liter. Filter before use. (iii) Preparation of working standard solution. Dissolve and dilute an accurately weighed portion of the azlocillin working standard with sufficient distilled water to obtain a concentration of 1.0 milligram of azlocillin per milliliter.

(iv) Preparation of sample solutions— (a) Product not packaged for dispensing (micrograms of azlocillin per milligram). Dissolve and dilute an accurately weighed portion of the sample with sufficient distilled water to obtain a stock solution of 1.0 milligram of azlocillin per milliliter (estimated).

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(b) Product packaged for dispensing. Determine both micrograms azlocillin per milligram of the sample and milligrams of azlocillin per container. Use separate containers for preparation of each sample solution as described in paragraphs (b)(1)(iv)(b)(1) and (2) of this section.

(1) Micrograms of azlocillin per milligram. Dissolve and dilute an accurately weighed portion of the sample with sufficient distilled water to obtain a stock solution of 1.0 milligram of azlocillin per milliliter (estimated).

(2) Milligrams of azlocillin per container. Reconstitute as directed in the labeling using distilled water in lieu of the reconstituting fluid. Then, using a suitable hypodermic needle and syringe, remove all of the withdrawable contents if it is represented as a singledose container; or, if the labeling specifies the amount of potency in a given volume of the resultant preparation, remove an accurately measured representative portion from each container. Dilute with distilled water to obtain a stock solution of convenient concentration. Further dilute an aliquot of the stock solution with distilled water to a concentration of 1.0 milligram of azlocillin per milliliter (estimated).

(v) Calculations-(a) Calculate the micrograms of azlocillin per milligram of sample as follows:

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Au-Absorbance of sample solution; Ps-Potency of working standard solution in micrograms per milliliter;

A, Absorbance of working standard solution; and

d=Dilution factor of the sample.

(2) Sterility. Proceed as directed in § 436.20 of this chapter, using the method described in paragraph (e)(1) of that section.

(3) Pyrogens. Proceed as directed in § 436.32(b) of this chapter, using a solution containing 100 milligrams of azlocillin per milliliter.

(4) Moisture. Proceed as directed in § 436.201 of this chapter, using the titration procedure and calculations described in paragraph (e)(2) of that section and preparing the sample as follows: Weigh the vial. Rapidly transfer a portion of the powder into the titration vessel, add the Karl Fischer reagent and restopper the vial immediately. Reweigh the vial to obtain the sample weight. A nitrogen purged glove bag or glove box should be used for preparing the sample.

(5) pH. Proceed as directed in §436.202 of this chapter, using an aqueous solution containing 100 milligrams of azlocillin per milliliter.

(6) Specific rotation. Proceed as directed in §436.210 of this chapter, using an aqueous solution containing 10 milligrams of azlocillin per milliliter and a 1.0-decimeter polarimeter tube. Calculate the specific rotation on an anhydrous basis.

(7) Identity. Proceed as directed in § 436.336 of this chapter.

[47 FR 53348, Nov. 26, 1982, as amended at 50 FR 1504, Jan. 11, 1985; 55 FR 11582, Mar. 29, 1990]

§ 440.2a Sterile amdinocillin.

(a) Requirements for certification—(1) Standards of identity, strength, quality, and purity. Sterile amdinocillin is 4thia-1-azabicyclo[3.2.0]heptane-2-car

boxylic acid, 6-[[(hexahydro-1H-azepin

1-yl)-methylene]amino]-3,3-dimethyl-7oxo-, [2S-2α,5a,6ẞ)]-. It is so purified and dried that:

(i) If the amdinocillin is not packaged for dispensing, its amdinocillin potency is not less than 950 micrograms and not more than 1,050 micrograms of amdinocillin per milligram on an anhydrous basis. If the amdinocillin is packaged for dispensing, its amdinocillin potency is not less than 950 micrograms and not more than 1,050 micrograms of amdinocillin per milligram on an anhydrous basis and also, each container contains not less than 90 percent and not more than 120 percent of the number of milligrams of amdinocillin that it is represented to contain.

(ii) It is sterile.

(iii) It is nonpyrogenic.

(iv) Its moisture content is not more than 0.5 percent.

(v) Its pH in an aqueous solution containing 100 milligrams of amdinocillin per milliliter is not less than 4.0 and not more than 6.2.

(vi) It is crystalline.

(vii) It gives a positive identity test for amdinocillin.

(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 the batch for amdinocillin potency, and if packaged for dispensing, amdinocillin potency and container content, sterility, pyrogens, moisture, pH, crystallinity, and identity.

(ii) Samples, if required by the Director, Center for Drug Evaluation and Research:

(a) If it is packaged for repacking or for use in the manufacture of another drug:

(1) For all tests except sterility: 10 packages, each containing approximately 300 milligrams.

(2) For sterility testing: 20 packages, each containing approximately 300 milligrams.

(b) If it is packaged for dispensing: (1) For all tests except sterility: A minimum of 15 immediate containers. (2) For sterility testing: 25 immediate containers, collected at regular intervals throughout each filling operation.

(b) Tests and methods of assay-(1) Amdinocillin potency and container content. Proceed as directed in §436.353 of this chapter, using ambient temperature, an ultraviolet detection system operating at a wavelength of 220 nanometers, a column packed with microparticulate (3 to 10 micrometers in diameter) reversed phase packing material such as octadecyl hydrocarbon bonded silicas, e.g., a Whatman ODS-3 column (25-centimeter column having an inside diameter of 4.6 millimeters and 5 micrometer particle size or equivalent), a flow rate of 1.0 milliliter per minute, and an injection volume of 20 microliters. Reagents, working standard and sample solutions, system suitability requirements, and calculations are as follows:

(i) Reagents-(a) Buffer solution 0.01M Transfer pH 5.0. 1.36 grams of monobasic potassium phosphate in sufficient water to make 1,000 milliliters of solution. Adjust the pH to 5.0 ± 0.1 with 18N phosphoric acid or 10N sodium hydroxide.

(b) Mobile phase. Mix acetonitrile (high-pressure liquid chromatography grade): 0.01M pH 5.0 phosphate buffer (15:85).

(ii) Working standard and sample solutions—(a) Preparation of working standard solution. Prepare the working standard solution fresh before injection by dissolving an accurately weighed portion of the amdinocillin working standard with sufficient distilled water to obtain a stock solution containing approximately 100 micrograms amdinocillin per milliliter.

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(b) Preparation of sampie solutions—(1) Product not packaged for dispensing (micrograms of amdinocillin per milligram). Dissolve an accurately weighed portion of the sample with sufficient distilled water to obtain a solution containing 100 micrograms of amdinocillin per milliliter (estimated). (2) Product packaged for dispensing. Determine both micrograms of amdinocillin per milligram of the sample and milligrams of amdinocillin per container. Use separate containers for preparation of each sample solution as described in paragraphs (b)(1)(ii)(b)(2) (i) and (ii) of this section.

(i) Micrograms of amdinocillin per milligram. Dissolve an accurately weighed

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