Study of Various Physical Parameters of Marketed Products of Paracetamol

Vamshi Krishna T., Girish Pai K., Hemanth G., Damodaram A., M. Sreenivasa Reddy

Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, INDIA

ABSTRACT:

The objective of this study was to compare various physical parameters of four different marketed brands of Paracetamol 500mg uncoated tablets and to verify the compliance of these physical parameters with respect to the standards as per Indian Pharmacopoeia (IP).The pre-requisite is that uncoated tablets should be free of dust without presence of any black particles and better tablet finish. Four brands of Paracetamol tablets manufactured by different manufacturers and but with similar primary package i.e. tablets packed in Blister were chosen and labelled as Brand A, B, C and D respectively. The tablets were randomly purchased from pharmacy outlets. The tablets were subjected to various physical evaluation tests like tablet appearance or description, weight variation, hardness, dissolution, disintegration time and friability. After performing the tests and comparing the results obtained, it was observed that all the four brands of Paracetamol tablets passed the Quality Control (QC) tests as per IP. However, the brands B and C showed poor physical appearance with observations like presence of dust, poor finishing, few chipped edges etc as compared to brands A and D. Among the brands A and D, brand D showed better results in terms of tablet appearance or description, weight variation, hardness, dissolution, disintegration time and friability. Thus brand D is concluded as best brand among four selected brands. The above said defects can be avoided by having strong in-process Quality Assurance personnel in the shop floor during manufacturing activity. A thorough monitoring system will avoid these observations and customer shall get a best tablet for medication.

KEYWORDS: Paracetamol, Appearance, Weight Variation, Friability, Hardness, Disintegration, Dissolution.

INTRODUCTION:

Acetaminophen, also known as paracetamol in other countries, is available widely without prescription as an analgesic and antipyretic. Chemically, paracetamol is N-(4-hydroxyphenyl) acetamide or 4-hydroxy acetanilide¹. Acetaminophen may be combined with other drugs, such as antihistamines or opioid analgesics, and marketed in cough and cold preparations, and allergy products. The chemical structure is depicted in figure 1.

Figure 1: Chemical Structure of Paracetamol

Paracetamol is a white crystalline powder or white crystals. Chronic, excessive acetaminophen consumption, defined as doses exceeding the recommended daily doses of 4 g for an adult and 90 mg/kg for a child for several days, has been associated with hepatotoxicity².

It is available in various oral dosage forms, including an extended-release preparation. But the most widely available dosage form is tablet. There are many companies producing these tablets with various brand names and with different prices. Our objective is to check whether these dosage forms comply with the requirements of Indian Pharmacopoeia mainly with respect to some physical parameters like appearance, friability, hardness, disintegration and dissolution^3-5.

MATERIALS AND METHODS:

Materials:

Four different brands of paracetamol 500 mg uncoated tablets were procured from retail pharmacy, potassium phosphate.

Equipment:

Weighing balance: FB-200 model of Essae,

Friabilator: EF-1W model of Electrolab,

Disintegration test apparatus: ED-2L model of Electrolab,

Dissolution Paddle Apparatus (I.P Type-I),

Hardness tester: Monsento,

Magnified lens to check the appearance of uncoated tablets,

UV-Visible spectrophotometer: Shimadzu UV 1601 PC

Miscellaneous items like Hand glove, butter paper, calculator etc.

Methods:

The tablets of all four brands were tested for physical parameters like appearance, weight variation, friability, hardness, disintegration time and dissolution as per IP³. The results were checked with Indian pharmacopoeia limits.

Appearance:

The appearance of uncoated tablets was checked visually against white background using a magnified lens for the presence of cracks, chipping, finishing of edges and colour.

Weight Variation:

This test was performed on 20 tablets. The weight of each tablet was measured using a digital weighing balance and the test was performed as per IP³.

Friability:

This test was performed by taking the required number of tablets as per IP³ and weighing them. The tablets were placed in the Friabilator for 4 minutes at 25 rpm and the difference in weight was noted. The percentage friability was then calculated using the formula

%Friability=

Hardness:

The hardness test was performed on 3 tablets of each brand using Monsanto Hardness Tester. The tablet was placed in the instrument and the pressure required to completely break the tablet was noted. The average hardness of the 3 tablets was calculated.

Disintegration:

This test was performed by taking the required number of tablets as per IP³ and placing them in the disintegration apparatus. The time required by the tablets to disintegrate was noted.

Dissolution:

This test was performed as per IP³ guidelines by using type I (paddle) dissolution apparatus and phosphate buffer pH 5.8 as the dissolution medium.

RESULTS AND DISCUSSION:

Appearance:

The tablets of brand A were circular, white coloured and had good appearance and glossy finishing. The tablets of brand B were circular, white coloured and showed the presence of rough edges and had poor finishing. The tablets of Brand C were circular, white coloured and showed deformations like chipping, sticking. The tablets of Brand D were circular, white coloured and showed good finishing. The results are tabulated in table 1.

Table 1: Physical appearance data:

Brand Name	Colour	Type of Packaging	Physical description
Brand-A	White	Blister	Circular tablet, good appearance and glossy finishing.
Brand-B	White	Blister	Circular tablet, rough edges and poor finishing
Brand-C	White	Blister	Circular tablet, poor finishing, lot of dust and few chipped edges
Brand-D	White	Blister	Circular tablet and smooth finishing

Table 2: Weight variation data

Tablet No.	Brand-A		Brand-B		Brand-C		Brand-D
Tablet No.	Weight of each Tablet (mg)	% Deviation	Weight of each Tablet (mg)	% Deviation	Weight of each Tablet (mg)	% Deviation	Weight of each Tablet (mg)	% Deviation
1	642	-0.47	610	-0.86	629	-2.80	565	-0.09
2	630	1.41	594	1.78	610	0.31	567	-0.44
3	633	0.94	609	-0.69	621	-1.48	573	1.50
4	641	-0.31	594	1.78	611	0.15	554	1.86
5	638	0.16	596	1.45	627	-2.47	554	1.86
6	635	0.63	594	1.78	612	-0.01	574	-1.68
7	631	1.25	606	-0.19	606	0.96	580	2.74
8	641	-0.31	606	-0.19	614	-0.34	568	-0.62
9	636	0.47	617	2.02	609	0.47	567	-0.44
10	627	1.88	608	-0.52	614	-0.34	569	0.80
11	637	0.31	609	-0.69	608	0.63	559	0.97
12	635	0.63	593	1.95	603	1.45	558	1.51
13	661	-3.44	611	1.02	608	0.63	553	2.04
14	634	0.78	596	1.45	612	-0.01	565	-0.09
15	633	0.94	600	0.79	603	1.45	553	2.04
16	640	-0.16	614	-1.52	616	-0.67	575	-1.86
17	657	-2.81	601	0.62	616	-0.67	563	0.26
18	649	-1.56	610	-0.86	621	-1.48	570	-0.97
19	645	-0.94	621	-2.69	607	0.80	562	0.44
20	635	0.63	607	-0.36	591	3.41	562	0.44
Avg	639		604.8		611.9		564.5

Table 3: Friability data

Brand Name	Weight of tablets before test (W₁), gm	Weight of tablets after test (W₂), gm	Weight loss (W₂-W₁), gm	% Friability
Brand-A	6.362	6.341	0.021	0.33
Brand-B	6.067	6.058	0.009	0.15
Brand-C	6.154	6.128	0.026	0.42
Brand-D	6.234	6.232	0.002	0.03

Figure 3: Friability

Table 4: Hardness data

Trial No.	Hardness (kg/cm²)
Trial No.	Brand-A	Brand-B	Brand-C	Brand-D
1	6.5	4.5	4	3.5
2	5	5.5	4	3.5
3	5	3.5	4	3.5
Average	5.5	4.5	4	3.5

Figure 4: Hardness

Disintegration Time:

Brand A showed the highest disintegration time whereas Brand D showed the least disintegration time when compared to other brands, but all the brands were within the IP³ limits of 15 min. The results are given in table5 and figure5.

Table 5: Disintegration data

Brand Name	Disintegration Time
Brand-A	< 4 mins
Brand-B	< 2 mins
Brand-C	< 2 mins
Brand-D	< 1min

Figure 5: Disintegration Time Profile

Dissolution

Brand-C showed the highest dissolution rate whereas Brand-A showed least dissolution rate when compared to other brands. The results are shown in the table6 and figure6.

Figure 6: Dissolution Profile

CONCLUSION:

The pre-requisite is that uncoated tablets should be free of dust without presence of any black particles, chipped edges and with a better tablet finish. Out of the four brands of uncoated Paracetamol tablets 500mg, brands B and C showed inferior physical appearance characteristics with observations like presence of dust, poor finishing, few chipped edges etc as compared to brands A and D. Among the brands A and D, brand D showed better results in terms of tablet appearance or description, weight variation, hardness, dissolution, disintegration time and friability. Thus brand D is concluded as best brand meeting all the requirements as per IP³. Above all, the description or physical appearance of brand D was pleasing without any dust, chipped edges etc. The above said defects can be avoided by having strong in-process Quality Assurance personnel in the shop floor during manufacturing activity.

A thorough monitoring system will avoid these observations and customer shall get a best tablet for medication. Where ever required, manufacturer must implement good manufacturing practices (GMP) and current GMP (cGMP) from time to time. For example, presence of dust in uncoated tablets can be avoided by using automated tablet de-duster during manufacturing operation. Tablets with defects like black particles and chipped edges can be rejected during tablet inspection activity. These steps will ensure that defect free tablet and best quality product will be made available to the patient community.

REFERENCES:

1. http://en.wikipedia.org/wiki/Paracetamol

2. Joseph T. DiPiro, Robert L. Talbert .In Pharmacotherapy- A Pathophysiologic Approach, 6th Edn, Tata McGraw Hill Publishing Company Limited, New Delhi, 2005 , 133- 134.

3. Pharmaceutical Methods, General Chapters, Indian Pharmacopoeia, 2007, 5^th edition, Vol-1, pp.177-183.

4. Vamshi Krishna T., Girish Pai K., M. Sreenivasa Reddy, Y. S. S. Kishan, V. Aditya, G. Bhanuprakash, M. Vishnu Datta. Study on the effectiveness of various types of primary packaging on the physical parameters of telmisartan uncoated tablets. 2012. Research J. Pharm. and Tech. 5(7): 962-967

5. Girish Pai K., Vamshi Krishna T., M. Sreenivasa Reddy, Y. S. S. Kishan, V. Aditya, G. Bhanuprakash, M. Vishnu Datta. Physical evaluation of the uncoated tablets of Glimepiride with different types of primary packaging. 2012. Research J. Pharm. and Tech. 5 (3):404-407

Received on 21.05.2013

Modified on 20.06.2013

Accepted on 28.06.2013

Research Journal of Pharmaceutical Dosage Forms and Technology. 5(4): July-August, 2013, 227-231

Time	% Cumulative drug release
Time	Brand-A	Brand-B	Brand-C	Brand-D
5	54.36	63.41	85.99	82.36
10	70.02	80.26	88.11	86.32
15	79.30	86.30	101.53	88.21
20	86.76	91.05	101.96	91.93
25	91.47	96.61	102.19	95.04
30	93.28	98.49	103.53	96.36