Date :

EXPERIMENT – 12
EVALUATION OF PREFORMULATION PARAMETER OF
PARACETAMOL IP
➢ Aim : To evaluate the preformulation parameters of paracetamol.

➢ Principle : Preformulation commences when a newly synthesized drug shows

sufficient pharmacological promise in animal models to warrants evaluation in man.
These studies should focus on properties of a new compound that could affect the drug
performance in development of efficacious dosage form. A thorough understanding of
these properties may ultimately provide a rationale for formulation design or support
the need for molecular modification.
THEORY
➢ Defnition : Preformulation involves the application of biopharmaceutical principles
to physicochemical parameters of drug substance are characterized with a goal of
designing optimum drug delivery system. Characterization of drug molecule is a very
important step of preformulation stage of product development.

• Name of the compound : Paracetamol.

• Chemical name : n-acetyl-para-aminophenol.
• Molecular formula : C 8 H 9 NO 2 .
• Molecular weight : 151.165 g·mol−1

• Description: White powder.

• Category: Pain and fever , nonsteroidal anti-inflammatory.
drug.

• Dose: 500 mg.

• Storage: Store protected from light and moisture.
The major Preformulation studies / Parameters of granules are as follows:
1. Bulk Density : It is defined as ratio of total mass of the powder to the bulk volume of
powder. It gives an idea about tablet porosity and its relationship with disintegration time and
hardness of a tablet. It is measured by pouring weighed powder into a measuring cylinder and
the volume is noted down. It is expressed in gm/ml and is given by :

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 Db = M / Vo
Where,
Db = Bulk Density , M = Mass of powder , Vo = Bulk volume of powder.
2. Tapped Density: It is defined as ratio of total mass of the powder to the tapped volume
of powder. Tapped volume is measured by tapping the powder to constant volume. It is
expressed in gm/ml and is given by:
Dt = M / Vt
Where,
Dt = Tapped Density. M = Mass of powder , Vt = Tapped volume of powder.
3. Carr’s Compressibility Index: It indicates the ease with which a material can be
induced to flow. it is the measure of potential strength that a power could build up in its arch
in a hopper and also the ease with which such an arch could be broken. Compressibility index
of the granules was determined by using the formula and it is expressed as a percentage and
is given by :
CI (%) = (Dt – Db) / Dt × 100
Where,
Dt is the tapped density of the powder. Db is the bulk density of the powder.
12.1 Table : Relationship between Carr’s index and flow property.
Carr’s Index Type of Flow
5-15 Excellent
12-16 Good
16-20 Fair
21-25 Passable
25-35 Poor
33-38 Very Poor
> 40 Extremely Poor

4. Hausner’s ratio : It indicates the flow properties of the powder and is measured by the
ratio of Tapped density (Dt) to the Bulk density (Db).
Hausner's ratio = (Tapped density) / (Bulk density)

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 12.2 Table : Relationship between Hausner Ratio and Flow Property

Hausner Ratio Flow Character

1.00 - 1.11 Excellent
1.12 - 1.18 Good
1.19 - 1.25 Fair
1.26 - 1.34 Passable
1.35 - 1.45 Poor
1.46 - 1.59 Very Poor
> 1.60 Extremely Poor

5. Angle of repose : It is the maximum angle possible between the surface of the pile of the
powder and the horizontal plane. The angle of repose was measured by using funnel method,
which indicates the flow ability of the granules.
Angle of repose is determined by the following formula.
tan θ = h/r
where,
θ = angle of repose , h and r are the height and radius of the powder cone.
θ = tan-1 h/r

12.3 Table : Relationship between Angle of reposes and flow property

Angle of Repose Type of Flow

<25 Excellent
25-30 Good
30-40 Fair / Passable
>40 Poor

6. Solubility Analysis : The solubility of drug is an important physicochemical property

because it effects the bioavailability of the drug, the rate of drug release into dissolution
medium and consequently, the therapeutic efficiency of the pharmaceutical product.
This is a valuable step in developing a formulation.

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Solubility is usually determined in variety of commonly used solvents and some oils if the
molecules are lipophilic.

12.4 Table : Solubility Parameter

Solubility Parts of Solvent Required for 1 Part of Solute

Very soluble Less than 1

Freely Soluble From 1 to 10
Soluble From 10 to 30
Sparingly Soluble From 30 to 100
Slightly Soluble From 100 to 1000
Very Slightly Soluble From 1000 to 10000
Practically Insoluble 10000 or more

METHODOLOGY

Bulk Density and Tapped Density : Pass a quantity of sample sufficient to complete
the test through a sieve, if necessary, to break up agglomerates. Into a measuring cylinder of
100 ml, gently introduce, without compacting, approximately 15g of the test sample and
weighed. Carefully level the powder without compacting, if necessary, and read the unsettled
apparent volume to the nearest graduated unit. Calculate the bulk density by applying the
formula.
The tapped volume is obtained by mechanically tapping the measuring cylinder containing
the sample of 15 gm with a fixed drop of 14±2 mm at a nominal rate of 300 drops per mins
until a constant volume is observed. Then calculate the tapped density using the formula.
After getting the value of bulk density and tapped density, Carr’s Compressibility Index
and Hausner’s ratio is calculated by using the formula.
Angle of repose : The static angle of repose was measured according to the fixed funnel
and free standing cone method. A funnel was clamped with its tip 2cm above a graph paper
placed on a flat horizontal surface. The powders were carefully poured through the funnel.
Block the orifice of the funnel by thumb. Fill the powder in the funnel and remove the thumb
immediately. After emptying the powder from the funnel, measure the height of the pile and
diameter.

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Solubility Analysis : The solubility of material is usually determined by the saturated/
equilibrium solubility method, which employs a saturated solution of the material, where
excess quantity of drug is taken in 10ml of each solvent and occasionally stirred for 24hrs at
room temperature and sample was filtered and filtrate was suitably diluted and analysed
spectro–photometrically at 249nm.

RESULT & CALCULATION

12.5 Table : Bulk density calculation
Weight of Sample(M) Volume of Sample(V0) Bulk Density of Sample(Db)
(Db = M / Vo)
1.82g 7.2ml 0.25g/ml

12.6 Table : Tapped density calculation

Weight of Sample(M) Volume of Sample(Vt) Tapped Density of Sample(Dt)

(Dt = M / Vt)

1.82g 3.5ml 0.52g/ml

12.7 Table : Carr’s index calculation

Bulk Density of Tapped Density of Carr’s Compressibility Index
Sample(Db) Sample(Dt) CI (%) = (Dt – Db) / Dt × 100

0.25g/ml 0.52g/ml 51.92%

12.8 Table : Hausner’s ratio calculation

Bulk Density of Tapped Density of Hausner's ratio .
Sample(Db) Sample(Dt) HR = (Dt /Db)

0.25g/ml 0.52g/ml 2.08

12.9 Table : Angle of repose calculation

Height of Radius of powder Angle of repose (ɵ)

powder cone(h) cone(r) θ = tan-1 h/r

3.5cm 3cm 49.12

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 12.10 Table : Solubility of paracetamol in different solvents

SL Solvent Absorbance Dilution Concentration Solubility (parts required to

No Factor (mg/ml) dissolve 1g of drug)

1 Water 0.219 100 0.009 1111ml (Very slightly

soluble)
2 Ethanol 0.352 100 0.0035 2857ml (Very slightly
soluble)

CONCLUSION : After performing the preformulation study of paracetamol , it is

concluded that the flow property of the powder paracetamol is extremely poor and it is very
slightly soluble in both water and ethanol.

Signature

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