II-C- CHECKING RAW MATERIALS

Transcription

1 II-C- CHECKING RAW MATERIALS II-C-1. II-C-1.1 II-C ACTIVE IN GREDIENT Specification and routine tests Active substance described in a Pharmacopeia : Zinc Sulfate Monohydrate Zinc sulfate monohydrate is an active substance defined in the American Pharmacopeia (USP), edition 28. Zinc sulfate is also defined in its heptahydrate form in the European Pharmacopoeia, 5th edition (EP) in monograph 01/2005 n As the finished product is the subject of a monograph in the USP, the active substance used must comply with the two monographs as follows ( In accordance with USP28, supplemented by EP 5th edition) : II-C ANALYSIS SPECIFICATIONS AND ROUTINE TESTS Analysis reference : Monograph USP28 supplemented by European Pharamacopoeia 5th edition 01/2005 n Date of last revision : 18 Nov Index n : 03 Caractères Characters Analysis Identification - Identification A) réactions des sulfates (EP2.3.1) Reactions of sulfates B) réaction du zinc (EP2.3.1) Reaction of zinc C) Dosage (EP2.5.11) Assay ESSAI Tests aspect de la solution S (EP et procédé 2) appearance of the solution Acidité (USP 28) Acidity chlorures (EP 2.4.4) chlorides Alcalins et alcalino-terreux (USP28) Alkalis and alkaline earths Arsenic (méthode ISO ) Arsenic Plomb ( norme USP28) Lead Fer (EP 2.4.9) Iron DOSAGE Assay ZnSO 4, H 2 O (EP ) Specification Aspect : poudre cristalline incolore à blanc,inodore, très soluble dans l eau, pratiquement insoluble dans l alcool. Appearance : white to colorless crystalline powder, odorless, very soluble in water, practically insoluble in alcohol Réaction positive Positive reaction Réaction positive Positive reaction satisfait aux limites du dosage. fulfils the assay limits limpide et incolore clear and colorless Absence de coloration rose par l orange de méthyle not colored pink by methyl orange TS Maximum 300ppm Maximum 0,9% Maximum 14ppm Maximum 0,002% (20ppm) Maximum 100ppm de 99,0 à 100,5% from 99.0 to 100.5% Partie II-C-3 Page 33 / 424

2 II-C QUANTITY SAMPLED Minimum 80 grams ( 20g for analysis and 60g for combinatorial library). II-C MONOGRAPH USP Partie II-C-3 Page 34 / 424

3 II-C ADDITIONAL TESTS IN ACCORDANCE WITH EUROPEAN PHARMACOPOEIA, 5TH EDITION Appearance : white to colorless crystalline powder, odorless, Solubility : very soluble in water, practically insoluble in alcohol PREPARATION SOLUTION S. Dissolve 2.5 g of zinc sulfate monohydrate in carbon dioxide free water R and make up to 50 ml with the same solvent. APPEARANCE OF SOLUTION S. Solution S is clear (EP 2.2.1) and colorless (EP 2.2.2, Procedure II). LIMIT TEST OF CHLORIDES (EP 2.4.4) : maximum 300 ppm. Take a sample of 3.3 ml of the solution S and make up to 15 ml with purified water. Decant the solution into a 20 ml test tube, add 1 ml of dilute nitric acid R, and pour this mixture in a single movement into a test tube containing 1 ml of silver nitrate solution R2. Prepare the control in the same conditions using a mixture of 10 ml of 5 ppm chloride solution (Cl)R and 5 ml of purified water. Inspect the test tubes sideways against a dark background. After 5 min. in a shaded place, if the solution to be inspected presents any opalescence, it is not more pronounced than in the control. LIMIT TEST OF IRON (EP 2.4.9) : maximum 100ppm. Take a sample of 2 ml of the solution and make up to 15 ml with purified water. Decant 10 ml of the solution into a test tube, add 2 ml of a solution of citric acid R at 200 g/l, and 0.5 ml of Thioglycolic acid R. Mix, alkalize with ammonia R and make up to 20 ml with purified water. Prepare the control in the same conditions using 10 ml of solution at 1 ppm iron (Fe) R. After 5 min. any pink coloring in the solution to be inspected is not more intense than in the control. II-C N/A II-C-1.2 Active substance not described in any Pharmacopeia Scientific data II-C Nomenclature Chemical name : Zinc sulfate monohydrate Synonym : Sulfuric acid, zinc salt monohydrate CAS : II-C Description Appearance : Solid, colorless to white, odorless. Empirical formula : ZnSO 4, H 2 O Molecular weight : 179,45 g/mol CAS registry number : [ ] II-C Manufacturer -Name and address of manufacturer MERCK KgaA Darmstadt Partie II-C-3 Page 35 / 424

4 Allemagne Tel : Trade name of the active substance : Zinc sulfate EMPROVE USP. Dr. Paul LOHMANN GmbH KG Hauptstraße-2 D Emmerthal Deutschland II-C Quality control during the manufacture of the active substance No supplier s data provided. II-C N/A Chemical development II-C N/A Impurities Partie II-C-3 Page 36 / 424

5 II-C Batch analysis Partie II-C-3 Page 37 / 424

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7 II-C II-C MERCK Documentation SUPPLIER SPECIFICATIONS Partie II-C-3 Page 39 / 424

8 II-C SUPPLIER STATEMENT Partie II-C-3 Page 40 / 424

9 II-C II-C Lohmann Documentation SUPPLIER GMP CERTIFICATE Partie II-C-3 Page 41 / 424

10 II-C SUPPLIER SPECIFICATIONS Partie II-C-3 Page 42 / 424

11 II-C SUPPLIER STATEMENT Partie II-C-3 Page 43 / 424

12 II-C Safety data sheet Partie II-C-3 Page 44 / 424

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