Lab 2

Assay of Aspirin using Back Titration

Aspirin is a

weak acid

that also undergoes molecule reacts with two hydroxide ions.

slow hydrolysis

; i.e., each aspirin To overcome this problem, a

known excess amount of base

is added to the sample solution and an HCl titration is carried out to determine the amount of

unreacted base.

This is subtracted from the initial amount of base to find the amount of base that actually reacted with the aspirin and hence the quantity of aspirin in the analyte.

Why do we use back titration?

Back Titration

In this technique. An accurately

known amount of a reagent

is added to analyte in such a way that some excess of the added reagent is left. This excess is then titrated to determine its amount and thus: mmol reagent reacted = mmol reagent taken - mmol reagent titrated Therefore, (the no. of mmol reagent reacted can be related to the no. of mmol of analyte from stoichiometry of the reaction between the two substance) can be determined since we know

mmol reagent added

and

mmol reagent titrated.

Mmol NaOH reacted= 2 Mmol Aspirin Mmol NaOH titrated= mmol HCl 2 mmol Aspirin= Mmol NaOH taken - mmol HCl Mmol aspirin = ½ ( 0.5 x 30) – ( 0.5 x 20)

Calculation of chemical factor and concentration of aspirin

1 CH 3 COOC 6 H 4 COOH + 2NaOH ---> CH

excess

Heat?

3 COO.Na + HOC 6 H 4 COO.Na + H 2 O 2 NaOH + HCl ----> NaCl + H 2 O 1 mole of aspirin = 2 moles of NaOH 180 gm of aspirin = 2 Equivalent no. of NaOH 180 gm/2 of aspirin = 1000 ml of 1N NaOH 90/2 gm of aspirin = 1000 ml of N/2 NaOH 0.045 gm of aspirin = 1ml of N/2 NaOH

0.045 gm of aspirin = 1ml of N/2 NaOH standard solution Conc. of aspirin

= ( ml of NaOH in excess x f " - ml of HCL titrant consumed x f " ) X

F

X f

Preparation of aspirin tablet solution

1- Take 10 tablets of aspirin

300mg

and

weight it

using sensitive balance .

2-

Grind the tablets

using mortar and pestle. 3-

accurate weight of powder equivalent NaOH

is added to it.

to

0.5gm

was taken and

30 ml 0.5 M 10 tablets

x 300mg = 3000 mg =3 gm (3.6 g) weigh you get it from the balance I want to take weight equivalent to (0. 5g) (??? gm) ???= this is the weight which must be taken from the grind tablets it is equivalents to 0.5gm aspirin.

Indicator

Indicators can be used to tell you when you have reached the Equivalence Point in a Titration.

However, different indicators must be used for different types of titrations.

pKa (indicator) = pH at Equivalent Point of Titration

To choose the best indicator for a particular titration,

Strong Acid-Strong Base Titration Curve

: The

best

indicators are the ones which have the

pH at EP within their Transition Range

.

So the best indicators for the SA-SB Titration would be: *

Bromthymol Blue (Range 6.0 – 7.6)

*

Phenol Red (Range 6.6 – 8.2

)

*Neutral Red (Range 6.8 – 8.0)

as these all have pH =7 within their transition ranges

Purity of a substance

• The substance used in the pharmaceutical field should be almost pure so that they can be safely used. It is rather difficult to obtain an almost pure substance • We find substances and chemicals with varying degree of purity.

Purity

of a substances depend upon several factors such as their methods of

manufacture

and ways of

crystallization

of

purification

processes.

• • In pharmaceutical field one deals with large number of drugs, chemicals and other substances which are used in formulations.

All such materials need to be pure. However, it is almost impossible to get an absolutely pure material, as impurities, may be in traces, do get incorporated in materials either during manufacture. Purification or in storage.

Permissible impurities in pharmaceutical substances

• Since it is not possible to avoid

impurities

, it is necessary to have substances which can be considered as of reasonably pure quality.

• The

pharmacopoeial committee

takes some points into consideration with regards to the problem of impurities in substances

Impurities which are of harmful type e.g., lead, arsenic etc, a low permissible limit is prescribed. This is based upon, (how much of these is to be tolerated)? Which itself is based upon, how much of the impurity is going to be harmful.

Impurities which are harmless type, the aim is to fix their limits such that their presence will not interfere in the therapeutic usefulness of a drug. Here again, the limits are prescribed and fixed. This is done depending upon the nature of the impurity, type of substance, use of substance The practicability of obtaining substance without impurities at reasonable cost. It may be possible to prepare substances (through series of steps of purification) without any impurity but this may be achieved at an exorbitant cost.

Deliberate adulteration using materials having similar qualities also accounts for the presence of impurities in the substances e.g: adulteration of potassium salt with sodium salt, calcium salts with magnesium salts etc. such adulteration bringing impurity into substances do not exhibit less therapeutic activity but it is reasonable expect adulteration material from ethical point of view

Pharmacopoeia:

1- British Pharmcopoeia 2- Unitated state Pharmcopoeia 3- European Pharmcopoeia

Official monographs of pharmaceutical chemicals and formulation generally describe

Description of the drug and product Test for identity Physical constants Quantitative analysis (i.e. assay ) of drug or the principle active constituents present in the formulation Limit test to exclude excessive contamination Storage condition Uses and doses

Test for purity

• • • Pharmacopoeias of various countries prescribe

tests for purity

for substances which are to used for

medical purpose.

The so called (

test for purity

) are as a mater of fact tests for detecting impurities in the substances.

Pharmacopoeias fix

limits of tolerance for these impurities

.

The governing factor for these is to determine how much impurity is likely to be harmful or bring about technical and another difficulties when the substance is used.

Limit test

• Limit tests are

quantitativ

e or

semi quantitative tests

designed to identify and control small quantities of impurity which are likely to be present in the substance.

• Limit tests must give some form of selective reaction with the trace impurity.

Limit test

• The sensitivity of some tests and the amount tolerated is such that a negative result (indicating the presence of only small permissible quantity of impurities) can be used as control.

• In many cases, a standard prepared from a prescribed amount of the impurity which is being tested, is compared with the sample under examination and the control is thus exercised.

• When comparing turbidity it should be done against black background.

• When comparing colored background.

it should be done against white

Nessler cylinders

Nessler cylinders

(also named

Color comparison cylinders

,

Color comparing cylinders

) are laboratory tube with a fixed volume , made of glass with optically plane bottom. On the walls there are marks of the nominal stroke volume (usually 100 ml) and possibly one half-way mark (then usually 50 ml) To minimize differences in the subjective impression of the color of the solution of the substance to be analyzed, cylinders of a series should have the same characteristics

height, diameter and thickness of glass.

Basically there are three types of used cylinders:

high with a capacity of 50 ml (about 300 mm in height, approximately 21 mm in diameter) low with a capacity of 50 ml (about 175 mm in height, approximately 25 mm in diameter) high with a capacity of 100 ml (about 375 mm in height, approximately 24 mm in diameter) low capacity of 100 ml (about 210 mm in height, approximately 34 mm in diameter) These parameters (except volume),

however, can vary significantly between two cylinders.