Miscellaneous Tests

Weight/mlTotal solidsLoss on dryingAsh test Toxicity testsMoisture contents

Weight per milliliter

Important for tinctures and extracts and defined as

The weight per milliliter of a liquid is the weight expressed in grams of 1 milliliter of a liquid when weighed in air at the specific temperature

Almost equal to density of the liquidFor this,

– Weigh a clean and dry pycnometer accurately

– Fill it with liquid, remove any access and weigh

– Determine the weight of liquid by subtraction

Determine wt/ml by dividing the weight of liquid that filled the pycnometer by the capacity of pycnometer

Expressed in g/ml

Total Solids (BP)

The term total solids is applied to the residue obtained when the prescribed amount of the preparation is dried to constant weight under the conditions specified

Total solids usually include extractives, both soluble in alcoholic or hydroalcoholic preparations as tinctures and extracts

Apparatus a hollow flat bottom, flanged dish 75mm in diameter 25mm deep made up of nickel or other metal

Place an accurately measured weight or quantity of the preparation after thorough shaking, say 10 ml in a tarred dish

Evaporate at as low a temperature as possible until the alcohol is removed, and heat on a water bath until the residue is apparently dry

Transfer to oven and dry to a constant weight at 105oC or dry in desiccator

Weigh the dish containing residueDifference in two weights is the

amount of total solid per 10ml.Determine total solid as g/100ml

Determination of Ash

Acid soluble ash Acid insoluble ash Water soluble ash Sulphated ash

Total ash

Clean dry silica crucible is heated and weighed to a constant weight. Then 2 g accurately weighed sample is taken in it and incinerated by gradually increasing heat to dull redness (675 ± 25 oC) until free from carbon. The crucible was then kept in desiccator and allowed to cool to a constant weight and weighed. The percentage of total ash with reference to air dried sample was calculated

Acid insoluble Ash

The total ash is boiled for 5 min in 25 mL dilute HCl. The insoluble matter is collected on ash less filter paper and washed with hot distilled water. The filter paper is then dried and ignited in tarred silica crucible until free from carbon. The crucible is allowed to cool in desiccator till a constant weight and weighed. The percentage of acid insoluble ash with reference to air dried sample is calculated

Sulphated Ash

Two gram accurately weighed sample is taken in tarred silica crucible, moistened with sulphuric acid and ignited gently. Crucible is then allowed to cool in desiccator and again moistened with sulphuric acid, reignited and weighed. The process is repeated till a constant weight is obtained. The percentage of sulphated ash with reference to air dried sample was calculated

Toxicity test

Usually performed on finished dosage form of toxoids and plastic containers in order to determine there safety or toxicity.

DIPHTHERIA TOXOID Inject IV/SC 4 healthy guinea pigs (300-400g) with a

of DT that is atleast 5 times the human immunizing dose (not less than 2ml).

Comply if no symptom of DT poisoning appear within 30 days.

TETANUS TOXOID Perform similar as DT but it is given SC. Check the symptoms of tetanus toxin poisoning after

21 days. PLASTIC CONTAINERS Extract of plastic containers used for parenteral

preparations is prepared. Its IV injection to mice determine its gross toxicity

and mortality.

Give IC into dorsal shaved skin of rabbit or

The standardized plastic strips are implanted

The local reaction is observed for toxicity.

Loss on drying

Test determines the amount of volatile matter of any kind that is driven of under specified conditions.

Take 1-2g of substance, reduce particle size if necessary, in a dried glass stoppered, weighed bottle.

Weigh and shake to evenly distribute the substance. Place the loaded bottle in drying chamber, remove

stopper and place it also in the chamber. Dry the sample at temperature specified in

monograph, close the bottle. Cool in desiccator & weigh

If the substance melts at a temperature at which loss on drying is to be performed, it is kept at 5 -10oC for 1-2 h for drying.

For substance requiring thermogravimetric analysis a sensitive electrobalance is used.

For vacuum drying vacuum desiccator or vacuum drying pistol are used.

Moisture Content

Heating method/thermogravimetry

Karl Fischer – Volumetric method– Coulometric method

Moisture contents

Accurately weighed powder (2 g) of the plant material is taken in a tarred silica crucible.

The powder is the dried in an oven at 105 oC for 30 min, cooled at room temperature in desiccator until constant weight and weighed to calculate the moisture contents.

The results are expressed as a percent of dry powder.

Karl Fisher Method---Standard technique for low moisture products.

Especially good for reducing sugars, protein-rich food and foods and pharmaceuticals with high volatile oils.

20Taiwan, September 2002

Karl Fischer

2 H2O + SO2 + I2 = H2SO4 + 2 HI

German Petrochemist,1901 – 1958

Publication: 1935

21Taiwan, September 2002

KF Reaction

SO2 + RN + ROH ------> (RNH)SO3R

a sulfite compound

(RNH)SO3R + H2O + I2 + 2RN ------> (RNH)SO4R + 2(RNH)I a sulfate compound

Summary

H2O + I2 + SO2 + 3RN + ROH ----->(RNH)SO4R + 2(RNH)I

The solvent (generally methanol) is involved in the reaction A suitable base keeps the pH 5 - 7

N NNNNNN NNNN

NN

H2O

CH3OH

H SO4CH3

I2 SO2 H I SO3

SO3

+ + + 2 +

+

Brown Mahogany Color

1.

2.

Karl Fisher Reagent: Dissolve Iodine in the mixture of Pyridine, MeOH and SO2.

Titrate 100 mg of H2O with Carl Fisher Reagent.

Calculate Concentration of K F Reagent =mg H2O /ml of Reagent

% H2O = Concentration x ml Reagent / mg of Sample x 100