Test Item Acceptance criteria Method reference
Appearance White or almost white, fine, free-flowing powder Visual Identification A Infrared Absorption should be concordant with
that of the reference standard. USP 197K Identification B An orange-yellow precipitate is formed
USP monograph Identification C A pale blue precipitate is formed.
Identification D A deep red color is produced.
Identification E The substance dissolves.
Nitrogen
determination NMT 0.05% USP 461
Residue on
ignition NMT 0.1% USP 281
Lead NMT 10 ppm
USP monograph
Limit of aldehydes NMT 0.05%
Limit of hydrazine NMT 1 ppm of hydrazine Vinylpyrrolidinon
e NMT 0.001%
2-pyrrolidone NMT 3.0%
Peroxides NMT 0.35
Formic acid NMT 0.5%
pH 3.0-5.0 USP 791
Water
determination NMT 5.0% USP 921
K-value 90.0%–108.0% USP monograph
2.3.P.4.2 Analytical Procedures
(a) Summary of the analytical procedures for supplementary tests:
There are three excipients used in the manufacturing of drug product Levofloxacin Tablets 500mg. All of the specification of the excipients are in line with the USP monograph.
2.3.P.4.3 Validation of Analytical Procedures
(a) Summary of the validation information for the analytical procedures for supplementary tests (where applicable):
All of the analytical procedures for excipients are introduced based on the corresponding USP monograph and general chapter. So the analytical procedures are not needed to be validated.
2.3.P.4.4 Justification of Specifications
(a) Summary of the validation information for the analytical procedures for supplementary tests (where applicable):
The specification including testing item and acceptance criteria for excipients are all in line with the USP monograph.
2.3.P.4.5 Excipients of Human or Animal Origin
(a) For FPPs using excipients without risk of transmitting agents of animal spongiform encephalopathies, a letter of attestation confirming this can be found in:
All excipients used in manufacturing of Levofloxacin Tablets 500mg are free of human or animal origin.
2.3.P.4.6 Novel Excipients
There is no novel excipient used in manufacturing of Levofloxacin Tablets 500mg.
2.3.P.5 Control of Drug Product (Levofloxacin Tablets 500mg) 2.3.P.5.1 Specifications
(a) Specification(s) for the FPP:
Table P5-1 Specifications for Levofloxacin Tablets 500mg
Tests Acceptance Criteria Analytical Procedure
Appearance White, Elongated film coated tablets. Visual examination
Identification A Meet the requirements USP <197U>:
Identification B
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
USP Monograph
Assay 95.0%–105.0% USP Monograph
Dissolution NLT 80% USP <711>
Uniformity of dosage units Meet the requirements USP <905>:
2.3.P.5.2 Analytical Procedures
(a) Summary of the analytical procedures (e.g. key method parameters, conditions, system suitability testing):
Appearance
White, Elongated film coated tablets by visual examination.
Identification
A: Ultraviolet Absorption <197U>
Solution: Dilute a portion of the clear filtrate used to pre pare the Assay preparation and a portion of the stock solution used to prepare the Standard preparation prepared in the Assay with Acidified methanol, prepared as directed for Dissolution, to obtain solutions containing about 10 mg of Levofloxacin per mL.
Identification B
The retention time of the major peak for Levofloxacin in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Assay
Method of Analysis: HPLC Chromatographic Condition:
Column: packed with octadecylsilane bond silica gel F low Rate: 1.2
Wave length : 220nm
Mobile Phase: 0.23% sodium laurilsulfate solution-methanol(60:40) Solvent mixer: mobile phase
Standard preparation: Dissolve a quantity of Levofloxacin CRS in water to produce a solution of about 2 mg per ml as the reference solution
Test preparation: Weigh accurately and powder 20 tablets. Dissolve an accurately weighted quantity of the powdered tablets, equivalent to about 0.1g Levofloxacin, in water in a 50 ml volumetric flask and shake thoroughly, Dilute to volume with water, mix well and filter. Take the successive filtrate as test solution.
Calculation= Levofloxacin acid%/tab.
Acceptance criteria: Not less than 95% and not more than 105% of the stated amount.
Dissolution
Medium: 0.1 N hydrochloric acid; 900 mL Apparatus 2: 50 rpm
Time: 30 min
Determine the amount of C12H15N3O2S dissolved using the following procedure.
Acidified methanol—To about 50 mL of methanol in a 100-mL volumetric flask add 2 mL of hydrochloric acid, dilute with methanol to volume, and mix.
Standard solution—Transfer about 90 mg of USP Levofloxacin RS, accurately weighed, to a 250-mL volumetric flask, add 10 mL of Acidified methanol, and shake to dissolve. Dilute with 0.1 N hydrochloric acid to volume, and mix. Transfer 5.0 mL of this solution to a 200-mL volumetric flask, dilute with 0.1 N sodium hydroxide to volume, and mix.
Procedure—Transfer 10.0 mL of a filtered portion of the solution under test to a 250-mL volumetric flask, dilute with 0.1 N sodium hydroxide to volume, and mix. Concomitantly determine the absorbances of this solution and the Standard solution at the wavelengths of maximum and minimum absorbance at about 308 nm and 350 nm, using 0.1 N sodium hydroxide as the blank. Calculate the quantity, in mg, of C12H15N3O2S dissolved by the formula:
22.5C(AU / AS)
in which C is the concentration, in mg per mL, of USP Levofloxacin RS in the Standard solution; and AU and AS are the differences in absorbance between 308 nm and 350 nm obtained from the solution under test and the Standard solution, respectively.
Uniformity of dosage units <905>:
Procedure for content uniformity—
Acidified methanol and Standard solution—Prepare as directed under Dissolution.
Test solution—Place 1 Tablet in a 500-mL volumetric flask, add about 300 mL of Acidified methanol, and shake by mechanical means for about 30 minutes. Dilute with Acidified
methanol to volume, and mix. Filter a portion of this solution, discarding the first 20 mL of the filtrate. Transfer 4.0 mL of the clear filtrate to a 200-mL volumetric flask, dilute with 0.1 N sodium hydroxide to volume, and mix.
Procedure—Concomitantly determine the absorbances of the Standard solution and the Test solution at the wave lengths of maximum and minimum absorbance at about 308 nm and 350 nm, using 0.1 N sodium hydroxide as the blank. Calculate the quantity, in mg, of
C12H15N3O2S in the Tablet taken by the formula:
22.5C(AU / AS)
in which C is the concentration, in mg per mL, of USP Levofloxacin RS in the Standard solution; and AU and AS are the differences in absorbance between 308 nm and 350 nm obtained from the solution under test and the Standard solution, respectively.
2.3.P.5.3 Validation of Analytical Procedures
(a) Summary of the validation information (e.g. validation parameters and results):
1. Summary of the Verification Results of Assay