Lab # 2: Comparative Dissolution Testing of Generic and Branded Paracetamol Tablets

IP4 - Group 4: Relos, Jillian Frexien T, Samson, Shannie Faye C., Uy, Janelle Andrea J.

ABSTRACT

I. INTRODUCTION

1
 II. METHODOLOGY

Using a dissolution machine equilibrated at 37°C, the corresponding paddle for each vessel was
attached. The dissolution vessels were then set into place and six of them were filled with 900 mL of pH
5.8 phosphate buffer. The height gauge for the paddle was then set. One tablet of a branded paracetamol
(Biogesic) was each placed in vessels 1, 2, and 3 while a generic paracetamol tablet in vessels 4, 5, and
6. The equipment was set at 50 rpm and run for 45 minutes. Afterwards, at 5, 10, 15, 20, 30, and 45
minute intervals, 20 mL sample from each vessel was withdrawn using a syringe and consequently
replaced with 20 mL of the buffer. The collected samples were then filtered. A volume of 1 mL filtrate was
diluted to volume with 0.1 M NaOH in a 50-mL volumetric flask. Absorbance readings of the samples
were then measured in triplicates by employing UV absorption to determine the amount of paracetamol
dissolved. The wavelength of maximum absorbance was set at 257 nm. The blank used was 0.1M NaOH.
Using 715 as the absorbance value of a 1% paracetamol solution at 257 nm, the total paracetamol
content in the medium in each time interval for all vessels were calculated.
To compare the dissolution profiles of the branded and generic paracetamol tablets, the similarity
factor and difference factor were calculated. The mean dissolution values from both curves at each time
interval were used for the computations. Assessment of the products were then made.

III. DATA AND RESULTS

Table 1.

The Absorbances, Paracetamol Concentration in vessel 1, and Percent Dissolution of Biogesic ®

(Branded) at different time points

VESSEL 1
TIME MEAN ABSORBANCE APAP IN THE BUFFER PERCENT APAP
± SD SOLUTION (g) DISSOLVED
5 0.028 0.0176224 3.5244755
10 0.213 0.1340559 26.8111888
15 0.189 0.118951 23.7902098
20 0.127 0.0799301 15.986014
30 0.321 0.202028 40.4055944
45 0.17 0.106993 21.3986014

Table 2.

The Absorbances, Paracetamol Concentration in vessel 3, and Percent Dissolution of Biogesic ®

(Branded) at different time points

VESSEL 3
TIME MEAN ABSORBANCE APAP IN THE BUFFER PERCENT APAP
± SD SOLUTION (g) DISSOLVED
5 0.021 0.0132168 2.6433566
10 0.118 0.0742657 14.8531469
15 0.168 0.1057343 21.1468531
 20 0.222 0.1397203 27.9440559
30 0.202 0.1271329 25.4265734
45 0.224 0.140979 28.1958042

Table 3.

The Absorbances, Paracetamol Concentration in vessel 4, and Percent Dissolution of Generic

Paracetamol (TGP) at different time points

VESSEL 4
TIME MEAN ABSORBANCE APAP IN THE BUFFER PERCENT APAP
± SD SOLUTION (g) DISSOLVED
5 0.007 4.40559 x 10-3 0.8811189
10 0.01 6.29371 x 10-3 1.2587413
15 0.014 8.81119 x 10-3 1.7622378
20 0.06 0.0377622 7.5524476
30 0.189 0.118951 23.7902098
45 0.16 0.1006993 20.1398601

Table 4.

The Absorbances, Paracetamol Concentration in vessel 5, and Percent Dissolution of Generic

Paracetamol (TGP) at different time points

VESSEL 5
TIME MEAN ABSORBANCE APAP IN THE BUFFER PERCENT APAP
± SD SOLUTION (g) DISSOLVED
5 0.004 2.51748 x 10-3 0.5034965
10 0.01 6.29371 x 10-3 1.2587413
15 0.016 0.0100699 2.013986
20 0.212 0.1334266 26.6853147
30 0.197 0.123986 24.7972028
45 0.215 0.1353147 27.0629371

Table 5.

The Absorbances, Paracetamol Concentration in vessel 6, and Percent Dissolution of Generic

Paracetamol (TGP) at different time points

VESSEL 6
TIME MEAN ABSORBANCE APAP IN THE BUFFER PERCENT APAP
± SD SOLUTION (g) DISSOLVED
5 0.001 6.29371 x 10-4 0.1258741
 10 0.001 6.29371 x 10-4 0.1258741
15 0.018 0.0113287 2.2657343
20 0.248 0.1560839 31.2167832
30 0.253 0.1592308 31.8461538
45 0.233 0.1466434 29.3286713

Using the theoretical absorbance of 1 % paracetamol, the concentration of paracetamol for x minutes in
each vessel can be calculated. For Vessel 1 of the branded paracetamol (Biogesic), the mean
absorbance was 0.028 at 5 minute.
1 % 𝐴𝑃𝐴𝑃 % 𝐴𝑃𝐴𝑃 𝑖𝑛 50 𝑚𝐿 𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛
=
715 0.028
𝑔
% 𝐴𝑃𝐴𝑃 = 3.91608 𝑥 10−5
𝑚𝐿
The calculated APAP concentration is from the measured absorbance of the diluted sample of 50 mL, but
since only an aliquot of 1 mL was used, the concentration of APAP in the aliquot should be calculated.
From the concentration of paracetamol in the aliquot, the amount of paracetamol in the buffer solution can
be calculated by multiplying it to the total volume of buffer solution used for dissolution.

3.91608 𝑥 10−5
𝑥 50 𝑚𝐿 𝑥 900 𝑚𝐿 = 0.0176224 𝑔 𝑜𝑓 𝑃𝑎𝑟𝑎𝑐𝑒𝑡𝑎𝑚𝑜𝑙
100 𝑚𝐿

Sample computation for the percentage of paracetamol that dissolved. The label claim of both generic
(TGP) and branded (Biogesic) paracetamol was 500 mg per tablet.
0.0176224 𝑔
𝑥 100 = 3.5244755 %
0.500 𝑔

The amount of paracetamol and the percent dissolution in the other vessels were calculated in the same
manner.

Table 6.

The Average Dissolution Values for Biogesic (Branded) and TGP (Generic) at Different Time Points
Average Percent Dissolution
Time Point (min)
Branded Generic
5 30.8391605 4.801865333 x 10-1
10 20.8321678 8.811098433 x 10-1
15 22.4685314 2.013986
20 21.9902098 32.7272726
30 32.9160839 26.8111888
45 24.792028 25.510485

Using the equation shown below, the difference factor (f1) is calculated.

∑𝑛
𝑡=1 (𝑅𝑡−𝑇𝑡)
𝑓1 = ∑𝑛
x100
𝑡=1 𝑅𝑡

Equation 1. Formula for Difference Factor

Where n is the number of time points, Rt is the dissolution value of the Reference batch (branded) for a
given time point and Tt is the dissolution value of the Test batch (generic) for a given time point.

∑ (𝑅𝑡 − 𝑇𝑡) = (30.8391605 − 4.801865333 𝑥 10−1 ) + (20.8321678 − 8.811098433 𝑥 10−1 )

𝑡=1
+ (22.4685314 − 2.013986) + (21.9902098 − 32.7272726) + (32.9160839
− 26.8111888) + (24.792028 − 25.510485) = 65.4139525
𝑛

∑ 𝑅𝑡 = 30.8391605 + 20.8321678 + 22.4685314 + 21.9902098 + 32.9160839 + 24.792028

𝑡=1
= 153.738181
65.4139525
𝑓1 = 153.738181 x 100 = 42.55

The computed difference factor is 42.55.

Using the equation shown below, the difference factor (f1) is calculated

100
𝑓2 = 50 𝑙𝑜𝑔
√1 + ∑𝑛𝑡=1 (𝑅𝑡 − 𝑇𝑡)2
𝑛
Equation 2. Formula for Similarity Factor

Where n is the number of time points, Rt is the dissolution value of the Reference batch (branded) for a
given time point and Tt is the dissolution value of the Test batch (generic) for a given time point.

∑𝑛𝑡=1 (𝑅𝑡 − 𝑇𝑡)2 = (30.8391605 − 4.801865333 𝑥 10−1 )2 + (20.8321678 − 8.811098433 𝑥 10−1 )2 +

(22.4685314 − 2.013986)2 + (21.9902098 − 32.7272726)2 + (32.9160839 − 26.8111888)2 +
(24.792028 − 25.510485)2 = 16.6060184

100
𝑓2 = 50 𝑙𝑜𝑔 = 99.70
√1 + 16.6060184
6

The computed similarity factor is 99.70.

IV. DISCUSSION

Dissolution refers to the process by which a solid phase goes into a solution phase such as
water. in essence, when a drug “dissolves,” solid particles separate and mix molecule by molecule with
the liquid and appear to become part of that liquid. Therefore, drug dissolution is the process by which
drug molecules are liberated from a solid phase and enter into a solution phase. (Sinko & Singh, 2011).
Biogesic® and Paracetamol from The Generics Pharmacy were the samples subjected in the dissolution
machine at different time points. Theoretically, the concentration of the paracetamol or or its dissolution
percentage in the sample should have been increasing through time. As shown in table 2. The

V. CONCLUSION AND RECOMMENDATION

It can be concluded in the experiment that the dissolution testing was successfully performed.
The results and the values calculated were properly evaluated. The calculated percent dissolutions of
both drugs were relatively low, and from the dissolution profiles of the two products, it can be concluded
that they are not similar. This is supported by the calculated values of the difference factor of 44.55% and
similarity factor of 99.70%. The conclusion is based on 6 vessels or 12 dosage units, which is the
requirement in comparative dissolution testing according to the US FDA. It is recommended to
immediately measure the absorbance of the samples to prevent possible degradation of the active
ingredient which can cause errors in the absorbance.
References

Singko, M. & Singh, Y. (2011). And Pharmaceutical Sciences (6th ed.) Baltimore Md, Lippincott Williams
& Wilkins, p.301
APPENDICES