1.

Uniformity of Weight

Diluent: MCC
The Weight Variation Tolerance (Pass
Individual % Weight / Fail)
Tablet No.
Weight (mg) Variation Column I Column II
1 550 -4.01 Pass Pass
2 590 2.97 Pass Pass
3 530 -7.50 Fail Pass
4 560 -2.27 Pass Pass
5 570 -0.52 Pass Pass
6 550 -4.01 Pass Pass
7 540 -5.76 Fail Pass
8 570 -0.52 Pass Pass
9 580 1.22 Pass Pass
10 570 -0.52 Pass Pass
11 530 -7.50 Fail Pass
12 620 8.20 Fail Pass
13 610 6.46 Fail Pass
14 550 -4.01 Pass Pass
15 610 6.46 Fail Pass
16 550 -4.01 Pass Pass
17 550 -4.01 Pass Pass
18 560 -2.27 Pass Pass
19 620 8.20 Fail Pass
20 650 13.44 Fail Fail
Average 573 Results 8 Fail 1 Fail
 Diluent: DCP
The Weight Variation Tolerance
Individual % Weight (Pass / Fail)
Tablet No.
Weight (mg) Variation Column I Column II
1 600 13.10 Fail Fail
2 590 11.22 Fail Fail
3 520 -1.98 Pass Pass
4 600 13.10 Fail Fail
5 540 1.79 Pass Pass
6 500 -5.75 Fail Pass
7 520 -1.98 Pass Pass
8 520 -1.98 Pass Pass
9 520 -1.98 Pass Pass
10 560 5.56 Fail Pass
11 500 -5.75 Fail Pass
12 520 -1.98 Pass Pass
13 520 -1.98 Pass Pass
14 550 3.68 Pass Pass
15 470 -11.40 Fail Fail
16 510 -3.86 Pass Pass
17 530 -0.09 Pass Pass
18 530 -0.09 Pass Pass
19 500 -5.75 Fail Pass
20 510 -3.86 Pass Pass
Average 530.5 Results 8 Fail 4 Fail
2. Thickness

Diluent: MCC
Variation of
Thickness Variation of Thickness
Tablet No.
(mm) thickness (%) within ±5 %
(Yes / No)
1 5.48 0.000 Yes
2 5.50 0.365 Yes
3 5.58 1.875 Yes
4 5.50 0.365 Yes
5 5.54 1.095 Yes
6 5.52 0.730 Yes
7 5.24 4.380 Yes
8 5.42 1.095 Yes
9 5.60 2.190 Yes
10 5.42 -1.095 Yes
Average 5.48 Results Yes

Diluent: DCP
Variation of
Thickness Variation of Thickness
Tablet No.
(mm) thickness (%) ±5 % (Yes /
No)
1 5.04 0.239 Yes
2 5.02 -0.159 Yes
3 5.04 0.239 Yes
4 4.92 -2.148 Yes
5 5.08 1.034 Yes
6 5.04 0.239 Yes
7 5.04 0.239 Yes
8 5.02 -0.159 Yes
9 5.26 4.614 Yes
10 4.82 -4.137 Yes
Average 5.028 Results Yes
3. Hardness test

Diluent: MCC Diluent: DCP

Variation of
Tablet Hardness Variation of Hardness
Tablet No. hardness
No. (kg/cm2) hardness (%) (kg/cm2)
(%)
1 0.50 -27.54 1 3.10 -25.12
2 0.50 -27.54 2 4.20 1.449
3 0.30 -56.52 3 4.20 1.449
4 0.90 30.43 4 4.90 18.35
5 0.80 15.94 5 3.90 -5.797
6 0.80 15.94 6 4.00 -3.381
7 0.70 1.449 7 4.10 -0.966
8 0.80 15.94 8 3.80 -8.212
9 0.80 15.94 9 5.00 20.77
10 0.80 15.94 10 4.20 1.449
Average 0.69 Average 4.14

4. Friability Test

Diluent MCC DCP

Initial Weight (mg) 5450.4 5447.5
Final Weight (mg) 5431.1 4969.7
5450.4 − 5431.1 5447.5 − 4969.7
Friability (%) × 100 × 100
Calculation 5450.4 5447.5
= 0.354 = 8.771
Friability (%) 0.354 8.771
Results Pass Fail

5. Disintegration Test
Diluent MCC DCP
Time (min) 1 >30
Results Pass Fail
6. Dissolution Rate Test

Table 1: Sample absorbance at 257nm

Diluent: MCC Diluent: DCP
Table

1 DF 2 DF 1 DF 2 DF
Time
(min)

5 0.493 X1 0.478 X1 0.704 X5 1.011 X5

10 0.823 X1 0.841 X1 1.328 X5 1.279 X5
20 1.297 X1 1.325 X1 1.710 X5 1.792 X5
30 1.672 X1 1.662 X1 1.974 X5 2.003 X5
40 1.975 X1 1.903 X1 2.271 X25 2.321 X25
50 2.159 X1 2.211 X1 2.480 X25 2.495 X25
60 0.591 X5 0.646 X5 2.101 X5 2.244 X125

Table 2: Cumulative % Drug Released from the Tablets

Concentration (g/mL) Cumulative % Drug Release

Diluent:
Diluent: DCP Diluent: MCC Diluent: DCP
MCC
Table

Time 1 2 1 2 1 2 1 2
(min)

5 10.47 10.16 14.88 21.31 2.692 2.613 19.131 27.399

10 17.37 17.75 27.94 26.91 7.159 7.177 55.054 61.998
20 27.29 27.88 35.93 37.65 14.176 14.346 101.250 110.405
30 35.14 34.93 41.45 42.06 23.212 23.328 154.543 164.482
40 41.47 39.97 47.67 48.71 33.876 33.606 460.993 477.618
50 45.32 46.41 52.04 52.35 45.530 45.540 795.536 814.154
60 12.52 13.67 44.11 47.10 61.627 63.116 852.249 2328.083

Tolerance value, Q (%) during 𝒕𝟑𝟎

MCC DCP
Tolerance, Q (%) 23.27 300
Results
(Pass when Q ≥ 80 % Fail Pass
during 𝒕𝟑𝟎 )
 7. Uniformity of Content of Active Ingredient

i. Preparation of Standard Graph of Paracetamol

Calibration curve of Paracetamol

Concentration (g/ml) Absorbance (Max. wavelength 257nm.)
5 0.224
10 0.445
15 0.730
20 0.977
25 1.205
30 1.391

Standard Graph (Absorbance against Concentration Graph)

1.6
Absorbance (Max. wavelength 257nm.)

y = 0.0478x - 0.0075
1.4 R² = 0.9965

1.2

0.8

0.6

0.4

0.2

0
0 5 10 15 20 25 30 35
Concentration (g/ml)

ii. Procedure for assay

Mass of Dose of Mass of Tablet in 100 mg of

Tablet Drug Paracetamol (API)
Type of Paracetamol (mg) (mg)
DCP 506.3 350 506.3
× 100 = 144.66 𝑚𝑔
350
MCC 558.6 350 558.6
× 100 = 159.60 𝑚𝑔
350
Marketed: Dynamol 500 556.3
556.3 × 100 = 111.26 𝑚𝑔
500
 Paracetamol
MCC DCP Marketed: Dynamol
Absorbance value

1 ml 0.418 0.333 0.417

2 ml 0.924 0.688 0.860

Concentration for Concentration for

Absorbance 1 ml, Absorbance 2 ml, % Purity
(g/ml) (g/ml)
Paracetamol

86.2700 + 97.5000
MCC 86.2700 97.5000 2
= 91.89
69.3750 + 72.8125
DCP 69.3750 72.8125 2
= 71.09
86.2500 + 90.9375
Marketed:
86.2500 90.9375 2
Dynamol
= 88.59
Table for Graph of Cumulative % Drug Release against Time.

Average of
Cumulative
% Drug
MCC DCP
Release

Time (min)

5 2.6525 23.2650
10 7.1680 58.5260
20 14.2610 105.8275
30 23.2700 159.5125
40 33.7410 469.3055
50 45.5350 804.8450
60 62.3715 1590.1660
Discussion:

1. Uniformity of Weight

Uniformity of weight is a test parameter to ensure the consistency of tablets during

compression, providing a precise dose of a drug. For tablets having average weight more than
250 mg, BP suggests that the tablets only pass the test when not more than 2 tablets have
the % weight variation tolerance more than 5.0 % for Column I, and none tablets have the %
weight variation tolerance more than 10.0 % for Column II. From the results shown,
Paracetamol using MCC as diluent fail as there are 8 fails for Column I and 1 fail for Column
II. While Paracetamol using DCP as diluent also failed the test as there are 8 fails for Column
I and 4 fails for Column II. Both MCC and DCP fail in both the test in Column I and Column
II. The results fail might be due to tooling of the compression machine, pressure applied,
difference in the density of the granulation and flow properties of the powder.

2. Thickness

Tablet thickness is important as it is essential for packaging and dosage range. Tablet
thickness is often affected by many factors such as compressive forces during manufacturing,
type of tabletting method, etc. For the test of thickness, the variation in thickness should be
within ± 5.0% only pass the test. From the results table shown for thickness, both type of
paracetamol, MCC and DCP pass the test as both of them have variation of thickness within
± 5.0%.

3. Hardness Test

Tablets hardness has a directly proportional relationship with disintegration rate. Tablets
should have hardness within acceptable range to disintegrate properly and withstand the
handling during coating, packaging and transporting. From the results shown, MCC and DCP
do not comply with the specification of USP as their hardness are lower than the range for
average hardness limit of 5 − 6 𝑘𝑔/𝑐𝑚2 . For MCC, the average hardness is 0.69𝑘𝑔/𝑐𝑚2.
For DCP, the average hardness is 4.14 𝑘𝑔/𝑐𝑚2. These indicate that both MCC and DCP
tablets are too soft which might be due to factors like amount of binder used is too less or
inappropriate method of granulation being used in preparing the tablet.
 4. Friability Test

Friability is the tendency for a tablet to chip, crumble or break following compression.
Tablets should have the ability to resist abrasion, but not too strong to affect drug release. A
maximum weight loss of not more than 1% of the weight of the tablets being tested is
required for the tablets to consider passing the test. From the results table shown, MCC has
friability of 0.354% which is less than 1% pass the test. Whereas DCP fail for the test as it
has friability of 8.771% which is exceeding the standard limit of less than 1%. Insufficient
binder used, low moisture content, poor tablet design, etc. might be reasons causing the DCP
paracetamol to fail the test.

5. Disintegration Test

Disintegration is the time required for tablets to disintegrate into particles under a given set of
conditions. This affect the effectiveness, absorption and therapeutic action of a drug. Based
on the parameters given, tablets only pass the test when they have met the specification of BP
of having disintegration time less than 15 minutes or met the specification of USP of having
disintegration time within the acceptable range of 5 – 30 minutes. From the results from the
table for disintegration test shown for uncoated tablets, MCC pass the test for USP and BP as
it disintegrates in 1 minutes, while DCP fail the test for USP and BP as it takes longer than 30
minutes to disintegrate. The results for DCP fail might be due to too much binder used,
leading to uneven distribution of the binder.

6. Dissolution Rate Test

Dissolution rate is the measure of the amount of drug enters a solution with respect to time
under standardized conditions. A drug must be able to release and dissolve in gastrointestinal
fluids before being absorbed into the bloodstream to be effective. Thus, dissolution rate
determines the rate and extent of drug absorption and bioavailability of a drug. A standard
graph, absorbance against concentration graph is being plotted to obtain an equation for the
calculation of cumulative % drug release. From the data obtained, Q (%) value which indicate
the test tolerance, Q (%) indicating amount of drug released, is obtained from graph of
average cumulative % drug release against time. Based on the table for Q (%) during t 30 for
dissolution rate test, Q= 17 %, which is lower than the standard of more than 80 % fails to
achieve the USP standard . For DCP paracetamol, it has Q= 103 %, which is more than 80 %
pass the USP standard. Fail in the results might be also due to errors being performed during
the process or characteristics and composition of the formulation like amount of ingredients
such as binder used.

7. Uniformity of Content of Active Ingredients (Assay)

Calculation is being performed for DCP paracetamol, MCC paracetamol and marketed
Dynamol paracetamol to get the mass of tablets in 100 mg of paracetamol (Active
Pharmaceutical Ingredient). A standard graph, absorbance against concentration graph is being
plotted which is then used to get the concentration of different type of paracetamol, DCP, MCC
and Marketed product Dynamol by comparing the absorbance value of 1 ml and 2 ml. The
value obtained is then used to calculate the % purity of drug in the tablets. Based on USP-24,
limit set for paracetamol assay is between 90-110 %. A limit of 95-105 % is set for the
paracetamol assay for BP. MCC has % purity of 91.89 %, so it passes the test for USP whereas
it fails the test for BP. DCP has % purity of 71.09 %, and marketed Dynamol has % purity of
88.59 %, indicating both the paracetamol product fail the test for both USP and BP. Purity of
paracetamol can also be compared, where MCC paracetamol being the purest, marketed
dynamol paracetamol being the next and finally goes for DCP paracetamol. The % purity might
be affected by degradation of the drug product itself or might be due to errors during the
experiment.
Conclusion:

From the results, MCC paracetamol is better than DCP paracetamol as MCC paracetamol
complies more with the specification although it does some fail in the test parameters. It is
essential for paracetamol, a non- prescription drug which is widely used by people to be
manufactured based on Good Manufacturing Practice (GMP), so that the product is of good
and acceptable quality. Test should always be performed to get the optimal quality drug
product. For a drug to be efficacious, the active pharmaceutical ingredients must be absorbed
into the systemic circulation and transported to its site of activity. Thus, drug products should
always meet with the specification of BP and USP which is required for a drug to have
therapeutic efficacy.