METHODICAL INSTRUCTION FOR STUDENTS OF THE 3rd COURSE

Pharmaceutical Faculty

 

LESSON № 6 (PRACTICAL – 6 HOURS)

 

Theme: Analysis of pharmaceuticals with acid-base properties.

Aim: : to acquire theoretical knowledge and practical skills under the analysis of quality of the medical products with acid-base properties.

 

Professional orientation of students:

Medical products of the inorganic nature, which own the acid-base property, are widely enough used in medical practice. Chloride acid apply at insufficient acidity of gastric juice (at insufficient of gastric acidity), and also to treatment hypochromia anemias in a complex with preparations of Iron (II). Acid boric and sodium tetraborate shows antiseptic, and sodium hydrocarbonate – antiacid, expectoric and anti-inflammatory action. The ammonia solution is reflex raises receptors of the respiratory centre, and also is sometimes used at carrying out of surgical operations for processing of hands of the medical personnel. Besides, the given substances are used as reagents in the pharmaceutical analysis.

At the heart of methods of identification, an establishment of high quality and quantitative definition of aforementioned preparations their acid-base of property lay.

Considering the theoretical material, concerning methods of reception, physical and chemical properties, techniques of identification, an establishment of high quality and quantitative definition of substances of medicinal substances of the above-named group, conditions of their storage and application in medical practice and the pharmaceutical analysis, students acquire knowledge which are necessary in the further professional work.

Performing practical work, students get new practical skills and improve earlier ones from the analysis of quality of substances of medical products.

 

Methodology of Practical Class

 

Sodium Bicarbonate

General Notices

(Sodium Hydrogen Carbonate, Ph Eur monograph 0195)

Natrii hydrogenocarbonas

 

NaHCO₃

Ээ

 

 

 

 

84.0ээ144-55-8

 

DEFINITION

Content

99.0 per cent to 101.0 per cent.

 

CHARACTERS

Appearance

White or almost white, crystalline powder.

Solubility

Soluble in water, practically insoluble in ethanol (96 per cent).

When heated in the dry state or in solution, it gradually changes into sodium carbonate.

 

IDENTIFICATION

эA. (BrPh, SPU, add. 1). Interaction with the indicators

To 5 ml of solution S (see Tests) add 0.1 ml of phenolphthalein solution R. A pale pink colour is produced. Heat; gas is evolved and the solution becomes red.

эB. (BrPh, SPU, add. 1). It gives the reaction of carbonates and bicarbonates (2.3.1).

Carbonates and Bicarbonates:  

Reaction with dilute acetic acid

Introduce into a test-tube 0.1 g of the substance to be examined and suspend in 2  ml of water R or use 2 ml of the prescribed solution. Add 3 ml of dilute acetic acid R.  Close the tube immediately using a stopper fitted with a glass tube bent twice at  right angles. The solution or the suspension becomes effervescent and gives off a colourless and odourless gas. Heat gently and collect the gas in 5 ml of barium hydroxide solution R. A white precipitate is formed that dissolves on addition of an excess of hydrochloric acid R1.

NaHCO₃  + СН₃СООН = СН₃СООNa + CO₂↑ + H₂O

CO₂ + Ва(ОН)₂  = BaCO₃↓ + H₂O

BaCO₃ + 2HCl = BaCl₂ + CO₂  + H₂O

эC. (BrPh, SPU, add. 1). Solution S gives reaction (a) of sodium (2.3.1)

Sodium and Sodium Salts:

A.                 Reaction with potassium pyroantimonate solution

Dissolve 0.1 g of the substance to be examined in 2 ml of water R or use 2 ml of the prescribed solution. Add 2 ml of a 150 g/l solution of potassium carbonate R and heat to boiling. No precipitate is formed. Add 4 ml of potassium pyroantimonate solution R and heat to boiling. Allow to cool in iced water and if necessary rub the inside of the test-tube with a glass rod. A dense white precipitate is formed.

NaНСO₃ + K[Sb(OH)₆] → Na[Sb(OH)₆]↓ + KНСO₃;

   Na⁺ + [Sb(OH)₆]^– → Na[Sb(OH)₆].

                                           white precipitate

 

Other reaction:

Reaction with saturated solution of MgSO₄ at boiling (carbonates formed white precipitate without heating, unlike bicarbonates):

2NaHCO₃ → Na₂CO₃ + CO₂ + H₂O (at heating)

4MgSO₄ + 4Na₂CO₃ + 4H₂O = 3MgCO₃^.Mg(ОН)₂^.3H₂O↓ + 4Na₂SO₄ + CO₂­

                                                           white precipitate

 

TESTS

Solution S

Dissolve 5.0 g in 90 ml of carbon dioxide-free water R and dilute to 100.0 ml with the same solvent.

Appearance of solution

Solution S is clear (2.2.1) and colourless (2.2.2, Method II).

Carbonates

The pH (2.2.3) of freshly prepared solution S is not greater than 8.6.

 

ASSAY

(BrPh, SPU, add. 1). Acidimetry, direct titration

Dissolve 1.500 g in 50 ml of carbon dioxide-free water R. Titrate with 1 M hydrochloric acid using 0.2 ml of methyl orange solution R as indicator.

1 ml of 1 M hydrochloric acid is equivalent to 84.0 mg of NaHCO3.

NaНСO₃ + HCl → NaCl + Н₂О + СO₂↑

E_m(NaНСO₃) = М.m.

Ph Eur

STORAGE

In densely corked container.

 

Action and use

Antacid; used in treatment of electrolyte deficiency.

 

Preparations

Sodium Bicarbonate Ear Drops

Sodium Bicarbonate Eye Lotion

Sodium Bicarbonate Intravenous Infusion

Sodium Bicarbonate Oral Solution

Compound Sodium Bicarbonate Tablets

Ph Eur

 

 

 

 

Boric Acid

General Notices

(Ph Eur monograph 0001)

Acidum boricum

H₃BO₃

 

Ээ

 

 

61.8ээ10043-35-3

Ph Eur

 

DEFINITION

Content

99.0 per cent to 100.5 per cent.

CHARACTERS

Appearance

White or almost white, crystalline powder, colourless, shiny plates greasy to the touch, or white or almost white crystals.

Solubility

Soluble in water and in ethanol (96 per cent), freely soluble in boiling water and in glycerol (85 per cent).

 

IDENTIFICATION

эA. (BrPh, SPU). Reaction of boron-methyl ester formation. Dissolve 0.1 g by gently heating in 5 ml of methanol R, add 0.1 ml of sulphuric acid R and ignite the solution. The flame has a green border.

Н₃ВО₃ + 3СН₃ОН ® (СН₃О)₃В + 3Н₂О

B. (BrPh, SPU). Interaction with the indicators. Solution S (see Tests) is acid (2.2.4).

 

TESTS

Solution S

Dissolve 3.3 g in 80 ml of boiling distilled water R, cool and dilute to 100 ml with carbon

dioxide-free water R prepared from distilled water R.

Appearance of solution

Solution S is clear (2.2.1) and colourless (2.2.2, Method II). pH (2.2.3) 3.8 to 4.8 for solution S.

 

ASSAY

(BrPh, SPU). Alkalimetry, direct titration. Dissolve 1.000 g with heating in 100 ml of water R containing 15 g of mannitol R. Titrate with 1 M sodium hydroxide, using 0.5 ml of phenolphthalein solution R as indicator, until a pink colour is obtained.

1 ml of 1 M sodium hydroxide is equivalent to 61.8 mg of H3BO3.

E_m = М m.

 

STORAGE

In densely corked containers.

 

Action and use

         Antiseptic agent.

 

Individual Students Program

1.    Latiames, synonyms of chloride acid, boric acid, ammonia solution, sodium bicarbonate, sodium tetraborate.

2.    Production of the above-stated preparations from mineral raw materials and chemical methods.

3.    Physical properties of substances of the given preparations.

4.    Reactions of identification of investigated preparations and feature of their performance.

5.    Sources of hit of specific impurities in a substance of aforementioned preparations and a technique of their definition.

6.    Techniques of quantitative definition of chloride acid, boric acid, ammonia solution, sodium hydrocarbonate, sodium tetraborate. Calculation molar weights of equivalents of defined substances.

7.    Physical and chemical properties of aforementioned preparations to prove of their storage conditions.

8.    Application of substances of medical products of the given group in medical practice and the pharmaceutical analysis.

 

Seminar discussion of theoretical issues

1.      What are latiames of sodium fluoride, sodium chloride, potassium chloride, sodium bromide, potassium bromide, sodium iodide, potassium iodide?

2.      What obtaining methods of this drugs do you know?

3.      What pharmacopoeial reactions of identification of afore-mentioned preparations do you know?

4.      What pharmacopoeial methods of assay of afore-mentioned preparations do you know?

5.      What storage conditions of afore-mentioned preparations do you know?

6.      What are actions and use in the medical practice of this drugs?

 

Test evaluation and situational tasks

1. The specific impurity in the substance of hydrochloric acid is:

       A. Heavy metals

       B. Sulfates

C. Arsenic

D. Iron

E. Chlorine

2. For identification of Sodium iones in the sodium tetraborate the pharmacist-analyst was used potassium pyroantimonate. What analytical effect of reaction?

A. Black precipitate

B. White precipitate

C. Yellow precipitate

D. Red precipitate

Е. Blue precipitate

3. For assay of ammonia can be used back acid-base titration. What indicator can be used?

A. Potassium dichromate

B. Solution of sodium eosine

C. Fluoresceine

D. Iron (ІІІ) ammonium sulphate

E. Methyl red

4. What is equivalent mass of boric acid, if for its titration alkalimetry it the mannitol solutions was used?

A. М m./2

B. М m./4

C. М m.

D. М m./3

            E. 2 М m.

5. What reagents for identification of sodium tetraborate by means of reaction of ester formation can be used?

A. Ethanol, dilute sulphatic acid

     B. Glycerol, chloride acid R

C. Chloride acid diluted, methanol

      D. Methanol, sulphate acid R

E. Mannitol, nitric acid R

1.    What volume of 0,1 M hydrochloric acid (f = 0,9989) for titration of 0,1095 g of sodium hydrocarbonate (M = 84,01 g/mol) will be used, if the percentage content of sodium hydrocarbonate in preparation is 99,1 %, and loss in weight at drying is 36,6 %.

2.    Calculate mass of  sodium tetraborate Na₂B₄O₇×10H₂O (M = 381,4 g/mol), if for titration was used: 15,70 ml of 0,1 M hydrochloric acid (f = 1,0058). The mass fraction of sodium tetraborate in a preparation is 100,1 %.

3.    Calculate the percentage content of boric acid (M = 61,8 g/mol), if for titration of 0,2008 g of boric acid was used: 16,10 ml of 0,2 M sodium hydroxide (f = 1,0000).

4.    What volume of 0,1 M hydrochloric acid (Кp = 1,0000) for titration of 5 ml of ammonia solution (M = 17,03 g/mol) will be used, if the percentage content of ammonia in solution is 10,05 %, volume of volumetric flask is 100 ml, volume of aliquot is 2 ml.

5.    Calculate,, if for titration of 10 ml of hydrochloric acid was used: 22,60 ml of 1 M sodium hydroxide (f = 1,0000).  Mass fraction of hydrochloric acid is 8,24 %.

 

Initial level of knowledge and skills are checked by solving situational tasks for each topic, answers in test evaluations and constructive questions.

(the instructor has tests & situational tasks)

 

Student should know:

1.    Latiames, synonyms, structure of medical products which show the acid-base of properties.

2.    Methods of reception of aforementioned preparations.

3.    Physical and chemical characteristics, methods of identification, establishment of high quality and quantitative definition of the given group of preparations.

4.    Conditions of storage and application of substances of medical products of investigated group in medical practice and the pharmaceutical analysis.

 

Student should be able to:

1.    To explain chemical processes which proceed at an establishment of identity, high quality and the quantitative maintenance of preparations which show the acid-base of property.

2.    Calculate molar weights of equivalents at definition of a mass fraction of operating substances in investigated substances methods of the acid-base of titration.

3.    After experiment carrying out to do a conclusion about conformity of quality of substances of medicinal substances to requirements of the AND.

 

Correct answers of test evaluations and situational tasks:

1. Е.   2. B    3. Е.    4. C.    5. D.

1. 8,2 ml.    2. 0,3008 g.    3. 99,1 %.    4. 5,9 ml.    5. 0,03446 g/ml.

 

References:

А – Basic:

1.     The International Pharmacopoeia / World Health Organization. – 3^rd Edition, Volume 5. Tests and general requirements for dosage forms; Quality specifications for pharmaceutical substances and dosage forms. – Geneva, 2003. – 371 p.

2.     European Pharmacopoeia /Directorate for the Quality of Medicines & HealthCare of the Council of Europe (EDQM). – Sixth Edition, Volume 1. – Strasbourg, 2007. – 1083 p.

3.     British Pharmacopoeia /published by The Stationery Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA). – Volumes I–IV. – London, 2009. – 10952 p.

4.     Pedersen O. Pharmaceutical chemical analysis: methods for identification and limit tests. – USA: Taylor and Francis Group, 2006. – 150 p.

5.     Lecture materials.

 

В – Additional:

1.     David G. Watson. Pharmaceutical analysis. – New York: Churchill Livingstone, 2000. – 400 p.

2.     Cairns D. Essentials of Pharmaceutical Chemistry. – Third edition. – London: Pharmaceutical Press, 2008. – 280 p.

 

 

Methodical instruction has been worked out by: associate professor L.M. Mosula

 

Methodical instruction was discussed and adopted at the Department sitting

on the 7-th of June 2012. Minute № 17