USP DISSOLUTION METHOD FOR

PARACETAMOL 500 MG TABLETS

ACETAMINOPHEN: C8H9NO2
AT. Bayan EL-Baou
THE EFFECTIVENESS OF TABLET OR CAPSULE DOSAGE FORMS RELIES ON THE DRUG
DISSOLVING IN THE FLUID OF GIT PRIOR TO ABSORPTION INTO SYSTEMIC CIRCULATION.
 Tablet Dissolution is a standardized method for : measuring the rate of drug release from a
dosage form.
 (Dissolution defined as the process by which a known amount of drug substance goes into
solution per unit of time under standardized conditions.)
THE PRINCIPLE FUNCTION OF THE DISSOLUTION TEST MAY BE
SUMMARIZED AS FOLLOWS:

 1. Optimization of therapeutic effectiveness during product development and stability

assessment.
 2. Routine assessment of production quality to ensure uniformity between production lots.
 3. Assessment of "Bioequivalence", that is to say, production of the same biological
availability from discrete batches of products from one or different manufacturers.
 4. Prediction of "in-vivo" availability i.e. bioavailability (where applicable).
 The rate at which a solid dissolves in a solvent was proposed by "Noyes and Whitney" in 1897 and
elaborated subsequently by other workers. The equation can be written as:
dC/dt = AD (Cs_C) / h*V

 A: surface area of exposed solid.

 D: diffusion coefficient.

 Cs: drug concentration in the diffusion layer (solubility of solid).

 C: drug concentration in the bulk.

 h: thickness of diffusion layer.

 V: volume of the dissolution medium. It is in the equation to make unit of the dissolution rate per unit
volume.
During early phase of dissolution, Cs (concentration in solution) >>>C (concentration in bulk) (sink
condition) and Cs is set to equal solubility in the dissolution medium (S), also A is considered constant thus
the above equation becomes:
dC/dt = KS, Where K is AD/ hV

K is called the intrinsic dissolution rate constant. Hydrophilic drugs have high intrinsic
dissolution rate as they have high S, while hydrophobic drug has low intrinsic dissolution rate.
* When K > 1, absorption process is not dissolution limited.
* When K < 1, absorption process is dissolution limited.
 EXPERIMENTAL PART:
a. Materials:
Otamol® 500 mg tablets, Acetaminophen (Paracetamol) powder, Monobasic Potassium
Phosphate, Sodium Hydroxide.
b. Apparatus:
 - Dissolution Apparatus.
 - UV/VIS Spectrophotomètre.
 - pH meter
c. Method:
NB: all equipment and tools should be cleaned prior to use.
C.1) Dissolution Parameters:
 Medium: Phosphate Buffer pH 5.8.

 Apparatus: Paddle.

 Time: 30 minutes.

 Volume: 900 mL.

 RPM: 50 rpm.

 Wavelength: at about 243 nm.

 Temperature: 37 °C ± 0.5 °C.

 Tolerance (Q): 80%.

C.2) Preparation of Phosphate Buffer pH 5.8 Solution:
1. Solution 1: Weigh accurately 20.42 grams of Monobasic Potassium Phosphate (KH2PO4) and place it in 500 mL
Volumetric Flask and adjust enough Double Distilled Water (D.D Water) to completely dissolve the powder then
complete the volume up to the 500 mL mark using D.Water.
2. Solution 2: Weigh accurately 0.43 grams Sodium Hydroxide (NaOH) and place it in 250 mL Volumetric Flask and
adjust enough Double Distilled Water to completely dissolve the powder then complete the volume up to the 250 mL
mark using D Water..
3. Transfer solution 1 and solution 2 to 3-liter V.flask and complete the volume up to the 3 liter mark with D.D.Water
then mix well.
4. Adjust the pH of the solution to achieve pH = 5.8 ± 0.1, using Phosphoric acid (if pH value where > 5.8) or NaOH
solution (if pH value where < 5.8) in order to adjust the pH
C.3) Procedure:
1. Turn the heater of the dissolution apparatus on and control the temperature to achieve the
specified value (37 °C).
2. Clean two vessels and in each of them place 900 mL of medium using measuring cylinder.
3. Fix the paddles to be 25 ± 2 mm away from the bottom of vessel.
4. Start operating the paddles at 50 rpm rotational speed.
5. Place one Otamol ® 500 mg tablet in each vessel (only two vessels will be used) and
immediately start timing.

NB: dissolution vessels should be covered to prevent evaporation of the dissolution medium and hence affecting the
concentration.
6. After 30 minutes elapsed withdraw 5-mL sample from each vessel using a volumetric pipette.
Filter each sample to get rid of any un-dissolved particles that may present in the sample) using
filter paper (always discard the first milliliter).
7. Dilute each sample, how? Withdraw 1 mL using volumetric pipette from each filtrate and
place in a clean 50 mL volumetric flask then complete the volume up to the 50 mL mark using
the medium.
8. Read the absorbance of the diluted samples solutions at λ = 243 nm using the medium
(Phosphate Buffer pH = 5.8) as a blank
C.4) Preparation of Standard Solution:
Calibration Curve:
a. Prepare 0.050gm% w/v of Acetaminophen in Phosphate Buffer pH 5.8 (Place 50 mg Acetaminophen in
100 mL Volumetric Flask, dissolve using few 10 mL of the solvent then complete volume up to the 100 mL
mark with Phosphate Buffer pH 5.8) → Standard Stock Solution

50 mg paracetamol-----------------------100 ml
b. Withdraw 1, 2, 3 & 4 mL from the Standard Stock Solution and place each in 50 mL Volumetric Flask
and complete the volume up to 50 mL mark with Phosphate Buffer pH 5.8 → Standard Solutions.
1st Conc.= 50 mg paracetamol---------------100 ml
?------------------------------------1 ml
?=(50*1)/100=0.5mg------------------put in total volume 50 ml
1st Conc.=0.5 mg paracetamol--------------------50 ml
?-------------------------------------1 ml
?= (0.5 *1)/50=0.01mg/ml
READ ABSORBANCE
2nd Conc.= 0.5mg paracetamol--------------50 ml volume
?--------------------------------2 ml

? = (2*0.5)/50=0.02mg/ml READ ABSORBANCE

3rd Conc.=0.5 mg paracetamol-----------------50 ml volume
? -------------------------------------3 ml
?=(3*0.5)/50=0.03mg/ml READ ABSORBANCE

4th Conc.= 0.5mg paracetamol------------------50ml volume

?------------------------------------------4 ml
?= (4*0.5)/50=0.04mg/ml READ ABSORBANCE

c. Measure the standard solutions absorbance using Phosphate Buffer pH 5.8 as a blank at λ = 243 nm.
RESULTS AND CALIBRATION CURVE
RESULTS AND CALIBRATION CURVE
RESULTS :
CALIBRATION CURVE CONSTRUCTION:
• Plot solutions absorbance vs their concentrations in gm%.
 A= a*b*C (beers law)
 Where A is the Absorbance, (a) is absorptivity (slope of the straight line equation), (b) is cell
bath (= 1 cm), and (C) is the concentration of the substance of interest.
 From excel/after requesting add trend line……we will get an equation:

y=a.x+b
y=will represent the unknown Conc.
a= slop ( will be given from the equation).
x= absorbance(x-axis)
b=y-intercept.
 UNIFORMITY OF DRUG CONTENT
 This test ensures content consistency of active drug substances within a narrow range around
label claim in dosage units.
 Non-compliance with this standard of the content of the active ingredient may be due to:

1- incorrect weighing of ingredients.

2-failure to achieve satisfactory mixing at the blending stage.
3- subsequent segregation of the components of the tablet formulation.
PROCEDURE:
 Standard preparation:
1) Take quantity of the 150mg of pure paracetamol powder, to 50 ml of 0.1M sodium hydroxide, dilute
with 100 ml of water, shake for 15 min, and then add water to produce 200 ml.
2) Mix, filter dilute 10 ml of the filtrate to 100 ml with water.
3) Add 10 ml of the resulting solution to 10 ml of 0.1M sodium hydroxide dilute to 100 ml with water &
measure the absorbance of the resulting solution at 257 nm.
4) Calculate the content of paracetamol, taking 715 as the value of A(1%, 1 cm ) at the maximum at 257
nm.
 Sample preparation:
1) Weigh 1 tablet of otamol, then crush the tablet using mortar and pestle.
tab wt. =x,……………each tablet contains 500 mg paracetamol.
2) Take quantity of the powder containing 150 mg of paracetamol, to 50 ml of 0.1 M sodium hydroxide, dilute
with 100 ml of water, shake for 15 min, and then add water to produce 250 ml
x mg-----------------500 mg paracetamol
? Mg-----------------150 mg paracetamol
3) mix, filter dilute 10 ml of the filtrate to 100 ml with water.
150 mg paracetamol-------------250 ml total volume
? -------------------------------10 ml
?=(10*150)/250= 6 mg paracetamol------put in total volume 100 ml--------6 mg/100 ml
4) Add 10 ml of the resulting solution to 10 ml of 0.1 M sodium hydroxide dilute to 100 ml with water & measure the
absorbance of the resulting solution at 257 nm.
6 mg paracetamol ----------------100ml
?-------------------------------10 ml
?=(10*6)/100= 0.6 mg paracetamol-----put in total volume 100 ml
Concentration is expessed as--------mg/ml
Theoretical conc.= (1*0.6)/100= 0.006 mg/ml
5)Calculate the content of paracetamol,715 as the value of A (1%,1cm)at the maximum at 257 nm.
The preparation complies with the test if, the content of active ingredient is in the range of (85-115)%, and the relative
standard deviation ( RSD= S/x*100%) is <= equal 6%
S: standard deviation.
X: mean.
 RESULTS & CALCULATION:
 Calculation & results presentation:

% paracetamol=
(Sample absorbance/ standard absorbance) * (standard concentration/sample concentration)*100%
note that: the theoretical conc. In both the sample & standard is = 0.006 mg/ml
RESULTS :
CALIBRATION CURVE CONSTRUCTION:
Plot solutions absorbance vs their concentrations in gm%.
 A= a*b*C (beers law)
 Where A is the Absorbance, (a) is absorptivity (slope of the straight line equation), (b) is cell
bath (= 1 cm), and (C) is the concentration of the substance of interest.
 From excel/after requesting add trend line……we will get an equation:

y=a.x+b
y=will represent the unknown Conc.
a= slop ( will be given from the equation).
x= absorbance(x-axis)
b=y-intercept.