Comparative Quality Assessment of 500mg Paracetamol Tablet Brands: Safety and Efficacy Analysis

Fig 1. Structure Of Paracetamol.⁴

Paracetamol, categorized as a non-steroidal anti-inflammatory drug (NSAID), undergoes multiple quality control assessments such as hardness, friability, weight uniformity, dissolution rate, and disintegration time, all of which are critical to ensuring its bioavailability and therapeutic impact.⁵ It can heighten the effects of anticoagulants like warfarin and acenocoumarin, which may increase bleeding risks. Often, paracetamol is blended with other agents, such as caffeine or codeine, or with oral decongestants for enhanced symptom relief in conditions like colds, flu, and sinus infections. Additionally, it is sometimes combined with opioid medications for managing severe pain associated with cancer, episiotomy, or post-surgical recovery.⁶ Selected as a model medication due to its easy accessibility, frequent use, and price variations across brands, paracetamol offers insights into the pharmaceutical market. Studies also highlight that paracetamol, unlike aspirin, is generally safer for  patients with high gastric acid production or extended bleeding time, making it a more tolerable option in such cases. ⁷

2. MATERIALS AND METHODS

Materials:

Preparation of buffer solution pH 5.8:

World Journal of Pharmaceutical Research For a pH of 5.8 dissolve 8.1654gm of sodium hydrogen ortho phosphate and 0.4gm of sodium hydroxide in enough distilled water to fill a volumetric flask with a 1000ml capacity.⁸,⁹,¹⁰

Instruments:

Analytical balance, UV-Spectrophotometer, Tablet hardness tester, Dissolution test apparatus, Disintegration test apparatus, Friability test apparatus.

Reagents:

Standard Paracetamol, Sodium hydroxide (NAOH), Potassium Dihydrogen orthophosphate (KH2PO4).

3. Evaluation tests for different brands

Objectives

The objectives of this research are:

• To evaluate and determine the major ingredients in the selected brands of paracetamol tablets
• To compare empirical data obtained from experimentation to the standard ones.
• To ascertain which brand is best or save for human consumption.

Merits

• This study focuses on the comparative analysis of different brands of paracetamol tablets available in the market. With the increasing demand for pain-relief medications in Liberia's healthcare sector, it is crucial to evaluate the quality of these products to minimize the circulation of substandard tablets. Instances of drugs in Liberia failing to meet quality standards highlight the importance of such research.¹¹
• This study aims to identify and examine the active ingredients of paracetamol tablets while evaluating their physicochemical properties across various brands. By doing so, it seeks to ensure that only effective and safe medications are available for public use.¹²

Limitations

• The study encountered several challenges that constrained its scope. One major limitation was the unavailability of essential equipment, such as a photo spectrometer capable of measuring wavelengths between 100 nm and 300 nm, and certain chemicals necessary for analgesic analysis. Additionally, the lack of appropriate solvents further restricted the research. Difficulties in scheduling access to laboratory equipment and arranging the distribution of chemicals from the university laboratory also posed significant challenges.
• Moreover, this study excluded key quality assessment methods such as hardness testing, disintegration time testing, dissolution testing, and friability testing, which are essential for a comprehensive evaluation of tablet quality. These limitations underscore the need for more extensive resources and planning in future research efforts.

Significance of the Study

This study offers significant benefits to various academic, medical, and regulatory groups in Liberia. Primarily, it enables the identification of which paracetamol brands meet quality standards for safe human consumption. Additionally, it serves as a critical reminder to pharmaceutical manufacturers and distributors about the presence of substandard or ineffective drugs in the Liberian market, encouraging them to maintain stringent quality control.13  For students and researchers, this study provides a well-structured approach and organized material that can guide similar research efforts. The techniques employed in this study could also be adopted and refined by regulatory bodies like the Ministry of Commerce. By incorporating these methods into standard protocols, the effectiveness and quality of imported pharmaceutical products could be more rigorously analyzed, helping to establish product-specific acceptance criteria and ensuring public safety.

Tests performed:

1. Friability: -

In this study, friability testing was conducted using a Roche Fabricator. A sample of 10 tablets was initially weighed and placed into the device, which was set to rotate at a speed of 25 revolutions per minute (rpm) for a total of four minutes. After completion of the test, the tablets were reweighed, and their final weights were compared to the initial weights to assess any weight loss. Friability in % was calculated by using formula.15

Fig 2. Friability Tester ¹⁵

Were,

% F = Percent friability

W? = Initial weight of the tablets

W = Weight of the tablets after rotation

2.Hardness test

Hardness refers to a tablet's ability to resist applied pressure. For this test, the tablet was positioned between the fixed and movable jaws of a Pfizer Hardness Tester. Pressure was applied to the tablet’s edge by gradually advancing the screw knob until the tablet fractured. The scale reading indicated the force needed to break the tablet.¹⁶ Tablet hardness is influenced by various factors, including the weight of materials, the spacing between the upper and lower punches during compression, and the level of pressure applied. Additionally, the type and quantity of ingredients in the formulation impact hardness. If the tablet is too hard, it may not disintegrate within the required timeframe, and if too soft, it may not withstand handling during packaging and transport.¹⁷

Fig 3. Monsanto Hardness Tester.¹⁸

3. Disintegration Test

The disintegration test assesses the time required for a tablet to break down into smaller particles, which is crucial for ensuring its proper dissolution and bioavailability in the body. In this test, six tablets were placed in a basket rack assembly attached to the disintegration apparatus. A 900 ml beaker filled with distilled water, maintained at a temperature of 37 ± 0.2°C (to simulate body temperature), was used as the medium. The apparatus allows for continuous movement of the basket up and down within the water, promoting uniform conditions for disintegration.¹⁹ The time taken for each tablet to completely disintegrate, without leaving any residue other than soft fragments, was recorded. This parameter helps confirm that the tablet will dissolve efficiently within the gastrointestinal tract, enabling the active ingredient to be absorbed and provide therapeutic effects.

Fig 4. Disintegration Test Apparatus.²⁰

The weight variation test is conducted to ensure that each tablet within a batch maintains uniformity in content, shape, size, and thickness. Consistency in weight is crucial for achieving accurate dosage and overall product quality. For this test, 20 tablets from each brand were selected and individually weighed using an analytical balance. The average weight of the tablets was calculated as a benchmark for comparison.²¹ Each tablet's deviation from the average weight was then determined, allowing the assessment of uniformity across the batch. The formula used to calculate the percentage of weight variation is as follows:

A tablet's weight is considered within acceptable limits if the deviation falls within the range specified by pharmacopeial standards, typically ±5% for tablets weighing more than 250 mg. This test ensures dosage accuracy, which is essential for both efficacy and safety in drug administration.²²

5.Dissolution

Apparatus No. 1

Medium 900 ml of phosphate buffer ph. 5.8

Speed and time 50 rpm and 30 min

Withdraw a suitable volume of the medium and filter and dilute a suitable volume of filtered with the same solvent measure the absorbance of the resulting solution at the maximum at about 243 nm similarly measure the absorbance of a solution of known concentration of paracetamol RS calculate the content of C8H9NO2 Do not less than 80% of the stated amount of C8H9NO2.²

Fig 5. Dissolution Test Apparatus.²⁴

USP defines content uniformity test for tablets containing less than <25 mg or less than <25% drug substance in case of coated or uncoated tablets

Determining the amount of drug in a simple of tablets (10)

The average drug content is calculated

The content of the individual tablets should fall within specified limits in terms of % deviation from the mean (85= 115%) if not comply repeat using 2a more tablets no one should be 75 – 125 % deviation. If uniformity test is required the weight uniformity test is not  required.²⁵

7.Thickness:

The thickness of individual tablet is measured with micrometer which gives us information about the variation between tablet's Tablet thickness should be within a +5% variation of a standard  value.²⁶

8.Size and shape

It can be dimensionally described and controlled the thickness of a tablet is only variations Tablet thickness can be measured by micrometer or by other Tablet thickness should be controlled within a +5% variation of standard value.²⁷

9.General appearances

The general appearance of a tablet 's identity and general elegance is essential for consumer acceptance for control of  uniformity and tablet to tablet uniformity The control of general appearance involves the measurement of size, shape, odor, taste etc...²⁸

10.Assay

To produce the standard calibration curve, 0.1 g of pure paracetamol was weighed and dissolved in a 100 ml volumetric flask. First, 10 ml of 0.1M sodium hydroxide was added to aid in dissolving the paracetamol, followed by 15 minutes of shaking with 100 ml of purified water. The solution was then diluted up to the mark to form a stock solution. Standard solutions of 1, 2, and 3 mg/ml were prepared by pipetting specific volumes of this stock solution into separate 100 ml flasks. Using a UV/visible spectrophotometer set to a wavelength of 243 nm, and a sodium hydroxide-water mixture as the blank, the absorbance of each standard solution was measured. These absorbance values were plotted against their respective concentrations to generate a calibration curve. A regression equation from this curve was then used to calculate the concentration of paracetamol in each test sample.²⁹

4. RESULTS AND DISCUSSION

Calibration Curve

Figure 6. Calibration Curve of Pure Paracetamol at Wavelength 243 Nm

Weight variation - According IP /BP the weight variation limits ±5% for the tablets 250mg or above 250 mg. In this study weight variation for all four different brands of paracetamol tablets within ±5% of their average weight were shown in Table 1.

Hardness test – Hardness always influences the friability and disintegration time. In this study the hardness result of all the different brand of paracetamol found satisfactory were shown in the Table 1

Friability test - The limit of Friability is not more than 1% according IP/BP. In this study we found that friability of all the tablets of different brands of paracetamol less than 1% were shown in Table 1.

Disintegration - According IP uncoated tablet disintegration time within 15 minutes. In this study all the tablets of different brand of paracetamol were completely disintegrated within 15 minutes which show in Figure 4.

Dissolution – According the IP the % release of drug is not less than 85% and, in this study, we found that the % release all different brands of Paracetamol above 85%. The result obtained satisfactory were shown in the Table 2 and Figure 5.

Assay – According to the BP the concentration of paracetamol is accepted if it is within the range of 90-110%. The assay test result for all different brands of paracetamol were found between in range 90 to 100%.

Table 2.  Weight variation ,Hardness, Friability, Disintegration, of Paracetamol.³⁰

Table 3.  In vitro drug release study of different brands of paracetamol in phosphate buffer.³¹