INDIAN PHARMACOPOEIA

13 as well as to the statements made in the monographs, test methods and appendices. Included, among other things, is the system of nomenclature of …...

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INDIAN PHARMACOPOEIA

REVISED GUIDE TO FORMATS

INDIAN PHARMACOPOEIA COMMISSSION

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INDIAN PHARMACOPOEIA Introduction: The Indian Pharmacopoeia (IP) is a compilation of official standards for drugs manufactured in India. The full name or title of the book is Indian Pharmacopoeia. Standards in the IP are expressed in the form of specifications and test methods for determining compliance with such standards. Specifications that are applicable to any pharmaceutical article are compiled in a monograph. A monograph states the quality or test parameters, the acceptance criteria and details of the tests that are to be performed to determine compliance with the criteria. In other words, a pharmacopoeial monograph provides a reliable basis for making an independent and objective judgement as to the quality of a pharmaceutical substance. As IP standards are statutory, it is important that the contents of monographs are unambiguous, acceptance criteria are clearly spelt out and the methods of evaluation provide all the details for carrying out the tests and assays, including the equipment, reagents and other ancillary materials that are to be used. To ensure that this requirement is uniformly and consistently met, guidance is provided in the following pages on the manner of drawing up of monographs and test methods and other relevant information. The exact manner of describing the tests, standards and reference to the general testing method numbers are also given. It shall be ensured that statements made in the monographs do not conflict with those stated in the General Notices, General Texts and with any information given in other sections of the Pharmacopoeia.

Contents of the Pharmacopoeia The technical part of the pharmacopoeia shall be broadly divided into the following sections: 1. Introduction 2. General Notices 3. Monographs 4. Test methods 5. Reagents and Solutions 6. General Texts 7. Index

1. Introduction The Secretary-cum-Scientific Director of the Indian Pharmacopoeia Commission (IPC) shall write this part after all the contents of the pharmacopoeia have been finalised. It shall briefly give the background to the edition and describe the salient features including the additions to and deletions from the previous edition.

2. General Notices The purpose of the General Notices is to provide the basic guidelines to the interpretation and application of the standards, tests, assays and other specifications of the pharmacopoeia, 12

as well as to the statements made in the monographs, test methods and appendices. Included, among other things, is the system of nomenclature of chemical compounds that is to be adopted. Recommendations on storage of drugs and specific labelling requirements may also be given. 3. Formats and Contents of Monographs General 1. A one-column format shall be used for all the pages of the monographs. 2. The font shall be ‘Times New Roman’ and the size for the text matter shall be ‘10 pt’ as given in the program ‘Microsoft Word’. 3. Capital letters, bold and italic types shall not be used indiscriminately since they have a special significance in the Pharmacopoeia. 4. Reagents, buffer solutions, chemicals other substances that are described or defined in the Pharmacopoeia shall be in italics. However, where a specific reagent is prepared for a specific test in a monograph and reference to it is made subsequently in the monograph it need not be in italics. 5. Italic types shall also be used for the systematic names of plants and microorganisms, and for some sub-headings of tests and texts (such as precautions to be observed while performing the tests, or which identification tests may be omitted etc) and for some parts of the chemical names. 6. The title of any monograph i.e. the name of the Pharmacopoeial substance shall be printed with initial letters in capitals and other letters in small case 7. Titles of monographs and headings of tests shall be in bold letters. The title shall be aligned on the left with the text. Synonyms, if any, shall be printed two spaces below the main title and shall not be in bold letters. 8. Single-line spacing shall be followed and the alignment of the text of the monograph shall be ‘justified’. Each test parameter and the accompanying text shall be separated from the other by a space of 1.5 lines. 9. Given in the following pages are directions on the manner in which the various tests and assays are to be described. Where the instructions are in red, the texts shall appear in the monographs in exactly the same way as shown.

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A. Active Pharmaceutical Ingredients (APIs) (Bulk Drug Substances) Chemical Excipients

The following, and in a few cases, some of the following information in this column shall be included in the monographs in the order given below Title of the Monograph

1. Name of the item printed in bold letters in font Times New Roman size 14 pt (MS Word). Subsidiary or abbreviated title or synonym (if any) may be shown two spaces below the main title (in ordinary letters) in font size 11 pt. The main monograph headings viz. Identification and Tests etc. shall be in Times New Roman size 11 pt, and the headings of the individual tests in size 10 pt and all in bold letters.

Example

Sodium Aminosalicylate Sodium PAS

Formula

1. Structural (Graphic) Formula 2. The molecular formula on the left and the molecular weight expressed to one decimal place on the right, two spaces below the graphic formula.

Chemical name

Examples

A statement of the chemical name, two spaces below the molecular formula in font size 10 pt, where the substance is a distinctly definable chemical entity, as follows: XXX is YYY, where XXX is the name of the item as given in the title of the monograph, and YYY is the chemical name sanctioned and employed by the International Union of Pure and Applied Chemistry (IUPAC).

1. Ethionamide is 2-ethylpyridine-4-carbothioamide. 2. Carbamazepine is 5H-dibenz(b,f)azepine-5-carboxamide Note- Guidance on steriochemical configuration, the sign of the optical rotation of enantiomers etc shall be given in the General Notices of the Pharmacopoeia.

Statement of purity

A definitive statement of the purity of the article, two spaces below Chemical name, and expressed in the following manner: AB contains not less than X per cent and not more than Y per cent of the chemical entity expressed as the molecular formula, calculated on the dried basis (where a test for loss on drying is specified), or on the anhydrous basis (where a test for water is specified), where AB is the pharmacopoeial name of the article, X and Y are the lower and higher percentage figures, respectively, expressed to one decimal place only.

Examples

1. Ethionamide contains not less than 98.5 per cent and not more than 101.0 per cent of C8H10N2S, calculated on the dried basis. 2. Cyclophosphamide contains not less than 98.0 per cent and not more than 102.0 per cent of C7H15Cl2N2O2P, calculated on the anhydrous basis. Note: With certain articles the measure of purity may not be the content of the chemical entity but some other factor such as potency or Unit of activity.

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Examples

1. Erythromycin has a potency not less than 920 Units per mg, calculated on the anhydrous basis. 2. Bacitracin Zinc has a potency of not less than 60 Units of bacitracin activity per mg, calculated on the dried basis.

Description

A brief description of the physical form of the material, including colour, texture, whether hygroscopic, odour, if readily apparent, and any other characteristic.

Examples

1.Description. A white, crystalline powder or colourless, transparent crystals. 2. Description. A pale yellow oil with slight, but not rancid odour.

Note- The indefinite article ‘a’ shall be used before the description Note: The following sections deal with the tests to be performed. Where reference is made to a general test procedure, the relevant number of the procedure is mentioned in brackets immediately after the test heading. However, in the following cases, the brackets may appear where the reference to the appendix is needed or at the end of the statement a) thin-layer chromatography, infrared absorption spectrophotometry etc., b) if the general test procedure is amended, the one to be adopted, c) when limits are to be given. In the former case, a dot should be put after the bracket and in the latter, a dot or comma depending on whether the text ends or continues, respectively. There should not be a comma before the brackets. Examples

Identification

pH (…….). 3.0 to 4.0 Arsenic (……). 5 ml of solution S complies with the limit test for Arsenic (2 ppm) Related substances. Determine by thin layer chromatography (…..), coating the plate with zzz At least two or three identification tests, starting with physical and instrumental tests and ending with general chemical reactions shall be given. The tests shall be marked with the letters A, B, C and so on followed by a dot and then the text after one space. The texts will naturally vary from test to test but given below is the mode of expression (indicated in red) of certain common tests: Infrared absorption spectrophotometry- This shall normally be the first identification test, where applicable. Determine by infrared absorption spectrophotometry (…..) (test appendix number to be put within the brackets). Where necessary, the specific manner of preparing the sample may be given. Compare the spectrum with that obtained with yyy RS (where yyy RS is the Reference Substance) or with the reference spectrum of yyy. Note- The acceptance criterion need not be repeated in the monographs. It shall be given in the test method itself.

Example

Identification. A. Determine by infrared absorption spectrophotometry (2.2.40). Compare the spectrum with that obtained with ceftazidime RS or with the reference spectrum of ceftazidime. B. UV Light Absorption (…….). The manner of preparing the solution of the substance under examination shall be given. The specific absorbance determined at the maximum at……nm is ….. to……

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Examples

Identification. A. Dissolve 20.0 mg in water and dilute to 100.0 ml with the same solvent. Dilute 10.0 ml of this solution to 100.0 ml with water. The specific absorbance (2.2.25) determined at 235 nm is 360 to 390. B. When examined between 230 nm and 360 nm (…….), a 1.0 per cent w/v solution of xxxx shows an absorption maximum at about ….nm C. Thin layer chromatography- Determine by thin-layer chromatography (…..), coating the plate with zzz. Mobile phase. The proportions of the constituents of the solvent mixture shall be given Test solution. The method of preparation shall be described. Reference solution The method of preparation shall be described. Procedure The method shall be described, starting with the volumes of solutions to be applied on the plate, the distance over which the mobile phase shall be allowed to run, treatment of the plate after development and manner of examination of the plate. The criterion for acceptance shall be indicated.

Example

Identification. C. Determine by thin-layer chromatography (2.2.27), coating the plate with silica gel F254. Mobile phase. A mixture of 6 volumes of butanol, 26 volumes of sodium acetate buffer pH 4.5, 32 volumes of butyl acetate and 32 volumes of glacial acetic acid. Test solution. Dissolve 0.10 g of the substance under examination in a 36 g/l solution of disodium phosphate and dilute to 2.0 ml with the same solution. Reference solution. Dilute 1 ml of the test solution to 200 ml with 36 g/l solution of disodium phosphate. Apply to the plate 2μl of each solution. Allow the mobile phase to rise 12 cm*. Dry the plate in a current of warm air and examine in ultraviolet light at 254 nm. The principal spot in the chromatogram obtained with the test solution corresponds to that in the chromatogram obtained with the reference solution * The height to which the mobile phase should be allowed to rise should be given only if it is different from 15 cm, the figure given in the general method. HPLC test- Usually when this procedure is used for the identification test the assay is also done by the same procedure. In such cases, the identification test shall state the agreement between the principal peaks in the chromatograms of the test and reference solutions.

Example

Identification. D. In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution. D. Where the HPLC test is used only for the identification test and not for the assay the manner of describing the test shall be similar to that given below in the examples for Related substances or Assay where such a test is to be employed, but the acceptance criterion will be as given in the example above except that the words “ In the Assay” shall be omitted. Chemical reactions- Texts depend on the nature of the tests.

Examples

1. Dissolve about 10 mg in 1 ml of sulphuric acid. An intense yellow colour develops.

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2. Dissolve about 10 mg in 2 ml of dilute hydrochloric acid and heat on a water-bath for three minutes. Add 3 ml of sodium carbonate solution and 1 ml of a 20g/l solution of sodium nitroprusside. A violet-red colour develops.

General chemical reactionsExamples

Identification. E. It gives reaction (a) of sodium (2.3.1)

Appearance of solution

Method of preparing the test solution to be given. The solution is clear (…….) and not more intensely coloured than reference solution xx or The solution is not more opalescent than opalescence standard……..(……..)

Example

Appearance of solution. Dissolve 4.0 g in 10 ml of water. The solution is clear (2.4.1) and not more intensely coloured than reference solution Y5 (2.4.1).

pH

Method of preparation of solution to be given. The pH of the solution is ….. to …..

Examples

pH. The pH of solution S is 4.0 to 5.0 (2.4.24). pH (…..). 3.5 to 4.5.

Specific optical rotation

+xxx to +xxx or -yyy to -yyy. The method of preparing the test solution may be given in some cases. Results to be reported to only one decimal place.

Example

Specific optical rotation (2.4.22). + 70.0 to + 73.0. Weigh accurately about 0.5 g, dissolve in water and dilute to 20.0 ml with the same solvent.

Related substances

Details of the method-usually by thin-layer, or liquid chromatography or gas chromatography shall be given.

Example

For Ethosuximide: Related substances. Determine by gas chromatography (2.4.13). See details in the Annexure.

Arsenic

Example

Heavy metals

Method of preparing the test solution shall be given. The resulting solution complies with the limit test for arsenic (…….) ( x ppm). Arsenic. Dissolve 1.0 g in 50 ml of water containing 2 g of citric acid and add 0.1 ml of stannous chloride AsT and 10 ml of hydrochloric acid. The resulting solution complies with the limit test for arsenic (2.3.10) (10 ppm). X g complies with limit test Y for heavy metals (a ppm).

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Example

Heavy metals (2.3.13) 2.0 g complies with limit test C for heavy metals (20 ppm).

Residual solvents

Determine by head-space gas chromatography (…….) using the ABC method. The content of xxxx is not more than …ppm, and the content of yyyy is not more than…..ppm. For ABC the specific method given in the test method section shall be stated, and for xxxx and yyyy, the names of the solvents shall be mentioned. Chromatographic system. The details shall be given

Microbial contamination

Total viable aerobic count (……) not more than Y103 micro-organisms per g.

Bacterial endotoxins

Bacterial endotoxins (….). Not more than XX Endotoxin Units per mg (2.2.3)

Example

Bacterial endotoxins (2.2.3): Not more than 0.25 Endotoxin Unit per mg of streptomycin.

Sterility

Sterility. it complies with the test for sterility (2.2.11)

Example

Sterility (2.2.11). Complies with the test for sterility.

Sulphated ash

Sulphated ash (2.3.18) Not

Water

Water (2.3.43). Not more than 2.0 per cent, determined on 0.5 g.

Example

Not more than……per cent, determined on XXX g by drying in an oven at xxxº to yyyº.

Loss on drying

Loss on drying (2.4.19) Not more than 1.0 per cent, determined on 5.0 g by drying in an oven at 100 to 105.

Example

Although there are many types of assay, they broadly fall into one or the other of the ones given here. The mode of writing them is:

Assay

HPLC method

more than 0.1 per cent.

Determine by liquid chromatography (2.4.14). Test solution. Directions for preparing to be given Reference solution. – do – Chromatographic system: - details of the column, - mobile phase composition, flow rate, - wavelength setting, - injection volume. Note- Commas are to be put after each item except the last where a full stop is to be given. Instructions for carrying out the determination, including the volumes to be injected, sequence of injections etc Calculate the percentage content of xxxx, where xxxx is the chemical entity mentioned in the opening purity statement. Example

Assay. Determine by liquid chromatography (2.4.14). 18

Test solution. Dissolve 25.0 mg of the substance under examination in water and dilute to 25.0 ml with the same solvent. Reference solution (a). A 0.1 per cent w/v solution of cefuroxime RS in water. (Dissolve 25.0 mg of cefuroxime RS in water and dilute to 25.0 ml with the same solvent. ) Reference solution (b). Warm 20.0 ml of reference solution (a) at 60º for 10 minutes. Cool and inject immediately. Reference solution (c). Dilute 1.0 ml if the test solution to 100.0 ml with water. Chromatographic system - a column 12.5 cm x 4.6 mm packed with hexylsilyl silica gel (5 μm), - mobile phase: 1 volume of acetonitrile and 99 volumes of acetate buffer solution pH 3.4, prepared by dissolving 6.01 g of glacial acetic acid and 0.68 g of sodium acetate in water and diluting to 1000 ml with the same solvent, - flow rate 1.5 ml per minute, - spectrophotometer set at 273 nm, - a 20 μl loop injector. . Inject reference solution (b). The test is not valid unless the resolution between the peaks due to cefuroxime and descarboylcefuroxime is not less than 2.0. In the chromatogram opbtained with reference solution (c), the tailing factor of the cefuroxime peak is not more than 1.5. Inject the test solution and reference solution (a). Calculate the content of C16H15N4NaO8S. By UV Light Absorption Method for preparing the test solution to be given. Measure the absorbance (……..) at the maximum at …..nm. Calculate the content of ……..taking the specific absorbance to be ….. Example

Assay. Weigh accurately about 50 mg in ethanol and dilute to 100.0 ml with the same solvent. Dilute 2.0 ml of the solution to 50.0 ml with ethanol. Measure the absorbance (………) at the maximum at about 240 nm.

By titrimetry Method for preparing the test solution to be given. Titrate with ………. Determine the end-point potentiometrically (………) Carry out a blank titration. 1 ml of titrant is equivalent to g of……. Example

Weigh accurately about 0.15 g and dissolve in a mixture of 10 ml of anhydrous acetic acid and 40 ml of glacial acetic acid. Titrate with 0.1M perchloric acid. Determine the endpoint potentiometrically (……) Carry out a blank titration. 1 ml of 0.1 M perchloric acid is equivalent to 0.01827 g of C6H15ClN2O2

Storage

Special storage conditions, if any shall be specified. Note: The type of container need not be given except in very rare cases. e.g. Store in single dose or multiple dose containers.

Examples

Store protected from light. Store in a tightly closed container, protected from light. Store protected from light and at a temperature not exceeding 30.

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labelling

Any special labelling statements specific to the product and also not stipulated in the Drugs Rules shall be given.

Examples

The label states whether or not the material is intended for the manufacture of sterile preparations. The label states, where applicable, that the substance is sterile.

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B. Inactive Ingredients other than Chemicals Drugs of Plant Origin

The following, and in a few cases, some of the following information in this column shall be included in the monographs in the order given below: Name of the item printed in bold letters in font size 14 (MSWord). Title of the Alternate titles, if any shall be given one space below the main title. Monograph

Opening Statement

The statement shall define the article.

Examples

Emulsifying Wax is a waxy solid containing 90 parts of Cetostearyl Alcohol, 10 parts of Sodium Lauryl Sulphate or sodium salts of similar sulphated higher primary aliphatic alcohols, and 4 parts of Purified Water. Activated Charcoal is obtained from vegetable matter by suitable carbonisation processes intended to confer a high adsorbing power.

Description, Identification and other tests, including Assay

These shall be expressed in the manner detailed above under Section A. Note- In the case of plant materials (not products derived from them), after Description the following shall be added, where applicable: It has (or they have) the macroscopic and microscopic characters described under Identification tests…..

Relative density

xxx to yyy. x and y shall be reported to three decimal places only.

Weight per ml xxxx g to yyyy g. X and Y shall be reported to three decimal places Refractive index

xxxx to yyyy. X and y shall be reported to three decimal places, unless otherwise stated.

Melting point

xxx to yyy

Freezing point

Not less than xxx

Viscosity

x mPa.s to y mPa.s

Peroxide Not more than xxx. Result shall be reported to one decimal place only. Acid value, value, Ester value

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UnsaponiNot less than xxxx. Values shall be rounded to the next higher integer. No fiable matter decimals to be used. Acetyl value, Hydroxyl value, Saponification value

Iodine value

xxx to yyy. Values shall be rounded to the next higher integer. No decimals to be used.

Acidity

Method of preparing the test solution and the indicator to be used to be given. Not more than x ml of yM sodium hydroxide is required to change the colour of the solution.

Example

To 1.0 g add 10 ml of ethanol and 0.1 ml of phenol red solution. Not more than ml of 0.01M sodium hydroxide is required to change the colour of the solution.

Not more than……. per cent. Foreign matter, Total ash, Ash insoluble in hydrochloric acid Storage

Labelling

Special storage conditions, if any shall be specified. Any special labelling statements specific to the product and also not stipulated in the Drugs Rules shall be given.

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C. Dosage Forms Title of the The following or some of the following information in this column shall be included in the monographs of dosage forms that contain synthetic APIs Monograph Name of the item printed in bold letters in font size 14 pt (MS Word). Alternate titles, if any shall be given one space below the main title size 11 pt (MS Word).

Example

in in font

Trimethoprim and Sulphamethoxazole Tablets Sulphamethoxazole and Trimethoprim Tablets. Co-trimoxazole Tablets

Definition/ Description

A definition of the preparation in terms of the active ingredient(s) together with information on its presentation except where the nature of the product is evident from the title. For parenteral preparations information shall be provided whether it is a solution, a suspension, a dry powder or a concentrate for dilution. Also to be mentioned is information on the nature of any additives (buffers, antimicrobial preservatives etc.) present; for other sterile preparations the nature of the vehicle shall also be stated. For tablets information on whether or not the tablets are coated and, if so, the type of coating shall be given.

Examples

Betamethasone Injection is a sterile solution of Betamethasone Sodium Phosphate in Water for Injections. Clotrimazole Cream contains Clotrimazole in a suitable base. Chloramphenicol Eye Drops are a sterile solution of Chloramphenicol in Purified Water. Aciclovir Oral Suspension is a suspension of Aciclovir in a suitable flavoured vehicle.

For injections that are supplied as solids that are to be constituted before use: Cefotaxime Injection is a sterile solution of Cefotaxime in Water for Injections. It is prepared by dissolving Cefotaxime Sodium for Injection in the requisite amount of Water for Injections before use.

Content statement

XXXX contain not less than……per cent and not more than……per cent of the stated amount of YYY (active ingredient), ZZZZZ (molecular formula). Alprazolam Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of alprazolam, C17H13ClN4.

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Examples

Salbutamol Inhaler contains not less than 80.0 per cent and not more than120.0 per cent of the amount of salbutamol, C13H21NO3 stated to be delivered by actuation of the valve.

Identification

Method of treating the sample and preparing the test solution shall be given, where required, followed by the details of the test in the manner shown in Section A.

Examples

A. Shake a quantity of the powdered tablets containing 50 mg of Bumetanide with 25 ml of ether, filter through anhydrous sodium sulphate and evaporate the filtrate to dryness. On the residue determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained with bumetanide RS or with the reference spectrum of bumetanide. B. Dissolve 20.0 mg of the contents of the capsules in water and dilute to 100.0 ml with the same solvent. Dilute 10.0 ml of this solution to 100.0 ml with water. The specific absorbance (2.4.7) determined at 235 nm is 360 to 390. C. In the Assay, the principal peak in the chromatogram obtained with the reference solution corresponds to the peak in the chromatogram obtained with the test solution.

Related substances/ Impurities

Tests for related substances or impurities arising on manufacture or storage of the dosage form shall be included. The tests applied to the bulk drug substance shall be applied, wherever possible with necessary modifications.

Examples

Related substances. Determine by thin-layer chromatography (2.4.17), coating the plate with silica gel F254. Mobile phase. A mixture of 60 volumes of 2-butanone, 20 volumes of 2methoxyethanol and 20 volumes of strong ammonia solution. Test solution. Shake a quantity of the powdered tablets containing about 0.25 g of Allopurinol with 10 ml of strong ammonia solution and filter. Reference solution. A 0.005 per cent w/v solution of 5-aminopyrazole-4carboxamide hemisulphate RS. Apply to the plate 10 μl of each solution. After development, dry the plate in a current of warm air and examine in ultraviolet light at 254 nm. Any secondary spot in the chromatogram obtained with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution.

Related substances. Determine by liquid chromatography (2.4.14) Test solution. Shake a quantity of the powdered tablets containing about 50 mg of Nevirapine in the mobile phase and dilute to 100.0 ml with the same solvent, filter. Reference solution. A 0.05 per cent w/v solution of nevirapine RS in the mobile phase. (Dissolve 25.0 mg of nevirapine RS in sufficient mobile phase to produce 50.0ml.)

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Chromatographic system - a column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 μm), - mobile phase: a mixture of 20 volumes of acetonitrile, 20 volumes of methanol and 60 volumes of a buffer solution prepared by dissolving 12.0 g of sodium dihydrogen phosphate in about 800 ml of water, adjusted to pH 3.0 with orthophosphoric acid and dilute to 1000.0 ml with water, - flow rate. 1.2 ml per minute, - spectrophotometer set at 230 nm, - injection volume. 20 μl. Inject the reference solution. The test is not valid unless the column efficiency is not less than 7500 theoretical plates, the tailing factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 2.0 per cent. Run the chromatograms five times the retention time of the principal peak. Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of any secondary peak is not more than the area of the principal peak in the chromatogram obtained with the reference solution (1.0 per cent) and the sum of the areas of all the secondary peaks is not more than twice the area of the principal peak in the chromatogram obtained with the reference solution (2.0 per cent).

Specific tests

Examples

Depending on the dosage form, details of any test parameter and the method of testing for it that is not included in the General Monograph on a Dosage Form, or is specific to a particular dosage form shall be given. For Ascorbic Acid Injection: Oxalic acid. Dissolve 0.25 g in 5 ml of water and neutralise to litmus paper with 2M sodium hydroxide. Add 1 ml of 2M acetic acid and 0.5M calcium chloride. Any opalescence, after 60 minutes, is not more intense than that produced by treating 5 ml of a solution prepared by dissolving 70 mg of oxalic acid in 500 ml of water in a similar manner (0.3 per cent).

For Aspirin Tablets: Salicylic acid. Shake a quantity of the powdered tablets containing 0.2 g of Aspirin with 4 ml of ethanol, dilute to 100.0 ml with water, filter immediately, transfer 50 ml of the filtrate to a Nessler cylinder, add 1.0 ml of freshly prepared acid ferric ammonium sulphate solution, mix and allow to stand for one minute; the violet colour produced is not more intense than that produced by adding freshly prepared acid ferric ammonium sulphate solution to a mixture of 3 ml of a freshly prepared 0.010 per cent w/v solution of salicylic acid, 2 ml of ethanol and sufficient water to produce 50 ml contained in a second Nessler cylinder (0.3 per cent).

For Tablets and Capsules: For Cyclophosphamide Tablets: Disintegration (2.9.1). 30 minutes.

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Disintegration For Piperazine Phosphate Tablets Example

Dissolution

Disintegration. The test does not apply to Piperazine Phosphate tablets intended to be chewed before swallowing.

Dissolution (2.5.2). - apparatus No., - medium volume and composition, - speed and time of rotation of spindle. The volume of medium to be withdrawn and subsequent operations for treating the aliquot and the manner of calculating the content shall be given. For Quinidine Sulphate Tablets:

Example

Dissolution (2.5.2). Apparatus No. 2, Medium. 900 ml of 0.1M hydrochloric acid, Speed and time. 100 rpm and 30 minutes. Withdraw a suitable volume of the medium and filter. Measure the absorbance (2.4.7) of the filtrate, suitably diluted if necessary at 248 nm. Calculate the content of (C20H24N2O2)2,H2SO42H2O in the medium from the absorbance obtained from a solution of known concentration of quinidine sulphate RS.

Other tests

Examples

Complies with the tests stated under xxxx, where xxxx stands for the title of the general monograph on the specific dosage form (where all the tests apply) Other tests. Comply with the tests stated under Tablets Other tests. The injection complies with the tests stated under Injectable Preparations (Powders for Injection).

Assay

Examples

Details of the method of preparation of the test solution shall be given followed by the further treatment of the solution for determining the content of active ingredient in the drug product. Where the method of assay is similar to that followed for the relevant API reference shall be made to that effect. In other cases, the actual details of the method shall be given. For Atenolol Tablets: Assay. Weigh and powder 20 tablets. Disperse a quantity of the powder containing about 0.2 g of Atenolol in 300 ml of methanol, heat the resulting suspension to 60 and shake for 15 minutes. Cool, dilute to 500.0 ml with methanol, filter and dilute a suitable volume of the filtrate with methanol to produce a solution containing 0.01 per cent w/v of Atenolol. Measure the absorbance (2.2.25) of the resulting solution at 275 nm. Calculate the content of C14H22N2O3 taking 53.7 as the specific absorbance at 275 nm.

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Directions for storing the product with particular reference to the nature of the pack and storage temperatures (as appropriate) shall be stated.

Storage

Protect the sealed container from light, at a temperature not exceeding 30. Store in a light-resistant container, protected from moisture.

Any specific requirement relating to the standard of the product or the storage directions shall be given. Labelling

Examples

The label states the quantity of the active ingredient in terms of the equivalent amount of amoxicillin. The label states (1) the number of Units per ml; (2) the species of animal from which the preparation has been made; (3) the name and proportion of any added preservative; (4) that the preparation, if liquid, should not be allowed to freeze; (5) that the preparation, if dried, should be used immediately after reconstitution in the stated quantity of the diluent.

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D. Vaccines, Immunosera and Products of Plant Origin ---------------------------------------------------------------------------------------The texts of the monographs shall be arranged in the following order: 1. An opening statement that defines the preparation Examples

Diphtheria Antitoxin is a preparation containing the specific antitoxic globulins or their derivatives and having the specific activity of neutralising the toxin formed by Corynebacterium diphtherae. The liquid preparation may contain a suitable antimicrobial preservative. Tetanus Vaccine (Adsorbed) is a sterile suspension prepared from tetanus toxoid containing not less than 1000 Limes flocculationis (Lf) per mg of protein nitrogen adsorbed on a mineral carrier. It contains a suitable antimicrobial preservative. Belladonna Dry Extract is a dried and powdered ethanolic extract of Belladonna Herb.

2. Production. The details of the method of producing the product shall be described. Example

For Diphtheria and Tetanus vaccine (Adsorbed) Purified diphtheria formol toxoid and purified tetanus formol toxoid are mixed with a suspension of a mineral carrier, which is hydrated aluminium hydroxide, aluminium phosphate or calcium phosphate, in saline solution or other appropriate solution isotonic with blood. The formol toxoids are prepared from the toxin produced by the growth in suitable media of Corynebacterium diphtheriae and Clostridium tetani respectively. The toxins are converted to toxoids by treatment with formaldehyde solution by methods, which avoid reversibility of the toxoids. The final product contains a suitable antimicrobial preservative. The antigenic properties of the vaccine are adversely affected by the presence of certain antimicrobial preservatives particularly those of the phenolic type.

3. Identification. Details of tests designed to specifically identify the article shall be given. Examples

S Specifically neutralises and renders the toxin formed by Cl. Tetani harmless to susceptible animals or by any other suitable in-vitro test. D Dissolve sufficient sodium citrate in the vaccine under examination to give a 10 per cent w/v concentration. Maintain at 37 for about 16 hours and centrifuge. The clear supernatant liquid reacts with a suitable tetanus antitoxin and yields a precipitate.

4. Tests. Details of specific tests including sterility, toxicity, potency or assay shall be given. Sterility. Complies with the test for sterility (2.2.11)

Examples

Potency. Carry out the biological assay of rabies vaccine (……..).

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.

E. General Monographs on Dosage Forms --------------------------------------------------------------------------------------The dosage forms for which General Monographs may be written are as follows: 1. Capsules 2. Ear preparations 3. Eye preparations 4. Granules 5. Liquids for oral use 6. Nasal Preparations 7. Parenteral preparations 8. Oral powders 9. Preparations for inhalation 10. Creams and Ointments 11. Rectal and vaginal preparations 12. Tablets The General Monographs shall be generally in three sections: 1. General description or definition of the dosage form and its different types. 2. Specific aspects of production that impact on the quality of the product. 3. Tests to be done in addition to the ones set out in the individual monographs.

4.Test Methods Test Methods shall be broadly divided into the following sections. a. Apparatus b. Physical and physicochemical methods c. Identification tests d. Limit tests e. Chemical assays f. Biological tests g. Pharmaceutical tests

5. Reagents and Solutions This section shall provide details of the quality and of preparation of reagents and solutions that are to be used in the tests and assays of the pharmacopoeia. It shall also include information on Reference Substances that are required for specific tests.

6. General Texts These shall consist of general information, not specific to any product, but pertaining to aspects of production and testing of pharmaceuticals impacting on quality, such as

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sterilisation, the quality of water for pharmaceutical use, containers (including closures) for packing drugs and drug products etc.

7. Index The Index shall be in alphabetical order of the titles of monographs, titles and sub-titles of test methods and of general texts, as well as of reagents and special solutions mentioned in any of the pages of the Pharmacopoeia except the cover page. The Annexures that follow show specimens of monographs in different formats for APIs, excipients, dosage forms etc.

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