A Comparative Analysis of In-Process Quality Control Parameters of Pantoprazole Gastro-Resistant Tablets

Pantoprazoleis an oral route medication falling under proton pump inhibitor (PPI) and completes its action within the gastric cell by reducing the production of gastric acids as per the dosage availability. Moreover, it acts as an antibacterial agent that inhibits the effects of Helicobacter pylori in the stomach. Most reports indicate that pantoprazole tablets are effective  and well-tolerated drugs worldwide for the treatment of gastric and duodenal ulcers and gastroesophageal reflux disease (GERD), including the management of acid-related disorders and the control and treatment of ulcers on the gastroduodenal due to non-steroidal anti-inflammatory diseases (NSAID). Pantoprazole also replaced benzimidazole to inhibit the blocking of the H+/K+ ATPase enzyme through  parietal cells,  thus inhibiting the secretion of gastric acid.[5]

Proton-pump inhibitors (PPIs):

Proton pump inhibitors (PPIs) inhibit gastric acid production specifically on the H+/K+- ATPase present in the gastric parietal cell. This involves the absorption of the PPI by the parietal cell. PPIs are weak bases; thus, protonation occurs in the acidic area of the secretory canaliculus of parietal cells. In secretory canaliculi, the methylsulfinyl group is a highly reactive sulfenamide. The last step is the covalent bonding of the reactive sulfenamide to 2
Cysteine residues of the catalytic subunit of the H+/K+- ATPase of the proton pump. This leads to the inhibition of acid secretion, followed by an elevation in intragastric pH.[6]

Drug profile:

Chemical structure:  

Formula: C16H15F2N3O4S

Molecular weight: 383.37 g/mol

Chemical name: 5-(trifluoromethoxy) -2-[[(3,4-dimethoxy-2-pyridinyl)

Methyl]sulfinyl]-1H-benzimidazole Sesquihydrate.

Appearance: White to off-white powder.

Properties: Freely soluble in water.[7]

MATERIAL AND METHODS

Materials

For comparative evaluation of Pantoprazole Gastro-resistant tablets (20 mg), four tablet brands from different pharmaceutical companies were purchased from the local market: PAN20, Pantop20, Pentab20, and PANTAKIND, and randomly coded as A, B, C, and D, respectively. List of different brands of Pantoprazole tablets and their type are shown in Table 1

Table 1: List Of Different Brands of Pantoprazole Tablets

Table 2: Instruments Used During the Comparative Study

Methods

The four brands designated as A, B, C, and D were subjected to quality control tests as described below.
1. Physical Appearance

2. Weight variation test

3. Thickness test

4. Hardness test

5. Friability test

6. Disintegration test

7. Preparation of Standard Calibration curve

8. Dissolution test carried out using the USP
Paddle II method and analysed using a UV
Spectrophotometer.[8][9]

1. Physical Appearance

The color and shape of the tablets were observed with the naked eye to verify their uniformity. Some companies have added grooves to the tablet surface to identify their brands. All of these features were determined through visual inspection.

1. Weight variation test

A weight variation test was conducted to ensure uniformity of the tablet weights. The weight of a tablet corresponds to the amount of medicinal component it contains. To verify consistency, tablet weights were frequently tested after manufacturing. In this study, 20 tablets were randomly selected and weighed. The average weight was calculated to determine the standard weight of a single tablet. The weight of each tablet was recorded individually and deviations from the acceptable weight range were noted. The standard limits of weight variation are listed in Table 3.[10]

Table 3: Standard Specifications of Weight Variation Tests

2. Thickness

Digital Vernier calipers were used to measure the tablet thickness. This provides information regarding the variation between tablets and provides precise measurements. Average results were determined using ten tablets.[10]

3. Hardness test

The hardness of tablets determines their resistance to capping, abrasion, or breakage during handling, storage, and transit before use. The load necessary to break or fracture a tablet resting on its edge is known as tablet hardness. This is occasionally referred to as the pillar crushing strength. Five tablets of each brand were ingested, and pressure was applied while the tablet was positioned between the spindles of the hardness tester. Then, the pressure was raised as gradually as possible until the tablet broke, the amount of pressure needed to do so was recorded and read from the device, and the hardness tester's sliding scale was calibrated to zero. I.P. states that the range is 4– 8 kg/cm².[11]

4. Friability test

The friability test for pantoprazole tablets determines tablet strength by evaluating the weight loss under pressure in a friabilator. Because pantoprazole tablets are enteric-coated tablets, they were weighed, rotated 100 times at 25 rpm, and then reweighed; the permissible level was ≤1%.[11]

5. Disintegration Time

The disintegration time test was performed as per the specifications. First, the disintegration tester was filled with 0.1N HCl and maintained at 37±2°C. Then, it was run for 2 h after placing six randomly selected tablets from each pantoprazole brand in the disintegration tester. Tablets were examined for signs of disintegration within 2 hrs running period. By changing the acidic fluid with phosphate buffer (pH 6.8 immediately after 2 h, the apparatus was operated for an additional 1 h at 37±2°C, and the disintegration time was noted. The tablets were considered completely disintegrated when all the particles passed through the wire mesh.[12]

7. Standard calibration curve

1. Preparation of Standard Stock Solution

Pantoprazole sodium (10 mg) was accurately weighed using an analytical balance and transferred into a 100 mL volumetric flask. The drug was dissolved in 100 mL of 0.1N HCl (or methanol, depending on solubility requirements) and sonicated if necessary for complete dissolution. The volume was made up to 100 mL using the same solvent to obtain a 100 µg/mL stock solution.

2. Preparation of Working Standard Solutions

Different concentrations were prepared from the stock solution by dilution with Phosphate Buffer (pH 6.8) to obtain concentrations of 0, 2, 4, 6, 8, and 10 µg/mL.

3. Measurement of Absorbance

The absorbance of each prepared concentration was recorded using a UV-Vis spectrophotometer at the maximum wavelength (λmax) of pantoprazole (usually approximately 294 nm, but should be determined experimentally). A blank solution (Phosphate Buffer, pH 6.8) was used for the baseline correction.

4. Plotting the Calibration Curve

A calibration curve was plotted by taking the concentration (µg/mL) on the X-axis and the absorbance on the Y-axis. A linear regression equation was derived to determine the correlation coefficient (R²) and to ensure good linearity.[14][15]

8.  Dissolution Study

Gastro-resistant (enteric-coated) tablets of pantoprazole sodium are dissolved in the intestine, where absorption takes place, avoiding stomach breakdown. To replicate the physiological conditions, a two-stage dissolving test was performed:

1. Acid Stage: Maintains the integrity of the enteric coating (0.1N HCl, pH 1.2).

2. Alkaline stage: Assess drug release under intestinal conditions using phosphate buffer (pH 6.8).

Reagents and Materials

• 20 mg gastro-resistant tablets of pantoprazole sodium

• 0.1N HCl (0.1N hydrochloric acid; pH 1.2)

• pH 6.8 phosphate buffer

• UV-visible spectrophotometer

• USP Type II (Paddle) Dissolution Apparatus

• Glassware:

Pipettes Methodology of Volumetric Flasks (1000 mL, 100 mL)

Phase 1: Acidic (pH 1.2, 0.1N HCl) Two hours

Procedure

1. Dissolution Medium: Add 750 mL of 0.1N HCl to each dissolution vessel.
2. Temperature Control: Maintain at 37 ± 0.5°C.
3. Stirring conditions: The paddle speed was set at 50 rpm.
4. Tablet placement One pantoprazole gastro-resistant tablet (20 mg) was placed in each vessel.
5. Sampling: Ten millilitres of the sample was withdrawn at 60, 90, and 120 min.
6. Filtration: The samples using a 0.45 µm membrane filter.
7. Analysis: Absorbance was measured using UV-Vis spectrophotometry at 290 nm.
8. Acceptance Criteria: No 10% of the drug should be dissolved in this phase, confirming that the enteric coating remains intact.

Stage 2: Alkaline Phase (pH 6.8 Phosphate Buffer) – Until Complete Dissolution

Procedure

1. Medium Replacement: After 2 h, the acidic medium was removed and replaced with 1000 mL of phosphate buffer (pH 6.8).
2. Temperature Control: Maintain at 37 ± 0.5°C.
3. Stirring conditions: the paddle speed was maintained at 50 rpm.
4. Sampling: Ten milliliters of the sample was withdrawn at 10, 20, 30, 45, and 60 min.
5. Filtration: The withdrawn samples using a 0.45 µm membrane filter.
6. Analysis: Absorbance was measured using UV-Vis spectrophotometry at 290 nm.
7. Acceptance Criteria: At least 80% of the drug should be dissolved within 60 min in phosphate buffer.[13]

RESULTS

1. Physical Appearance

The color, surface, and shape of the tablets were visually inspected. The physical appearances of the different pantoprazole brands are shown in Table 4.

Table 4: Physical characteristics of Pantoprazole tablet

2. Weight Variation Test

A weight variation test was conducted to assess the uniformity of tablet weight in accordance with pharmaceutical standards. A random sample of 20 (n = 20) pantoprazole tablets (20 mg) was selected and individually weighed using a calibrated analytical balance. Average weight was determined by dividing the total weight of the sample by 20. The weight variation of the tablets was calculated using the following formula:

Upper Limit = Average Weight + (7.5/100×Average weight)

Lower Limit = Average Weight - (7.5/100×Average weight)

According to USP/BP guidelines, tablets with an average weight between 80 and 250 mg must not deviate beyond ±7.5% of the mean weight. The batch was considered acceptable if no more than two tablets exceeded this limit and none deviated beyond ±15%. This test ensures consistency in tablet weight, which is critical for maintaining a uniform drug content and efficacy.

Table 5: Calculations and results of weight variation

Fig. 2: Weight Variation of Diff. Brands

3. Thickness

The thicknesses of different brands of Pantoprazole Tablets (20 mg) were determined using a digital Vernier caliper, and the results are listed in Table 6.

Table 6: Individual thickness of tablets and results

Graphical Representations of The Average Thicknesses of The Individual Brands Are Shown In Fig 3.

4. Hardness

The hardness of the different brands of pantoprazole tablets (10 mg) was determined using a digital hardness tester, and the results are listed in Table 7.

Table 7: Hardness of tablets and results

Fig. 4 Hardness of Diff. Brands of Tablets

5. Friability Test

The friability of the different brands of Pantoprazole Tablets (10 mg) was determined using Roche Friability instruments for 4 min at 25 rpm, and the results are listed in Table 8.

Table 8: Friability of tablets

A graphical presentation of the friability of the individual brands is shown in Fig 5.

Fig. 5:  Friability of diff. brands

6. In Vitro Disintegration Test

The test for decomposition time was performed according to the specifications. First, the disintegration tester was filled with 0.1 N HCl and maintained at 37 ± 2 °C. It was also run for 2 h after placing the six tablets from each pantoprazole brand in the decomposition tester. Tablets were examined for signs of decomposition within 2 hrs running period. By changing the acidic fluid with phosphate buffer (pH 6.8 incontinently after 2 h, the outfit was operated for 1 h at 37 ± 2 °C, and the decomposition time was noted. The tablets were considered fully disintegrated when all the patches passed through the line mesh.

Table 9: Disintegration of tablets

7. Standard Calibration Curve for Pantoprazole

The calibration curve of the standard was drawn by plotting the Absorbance against Concentration. Figure 7 shows the standard calibration curves. A correlation coefficient greater than 0.9999 reflected the occurrence of homogeneity in the concentration range of 0 – 10μg/ml. The absorbance of the Pantoprazole tablet was
Measurements were performed using a UV spectrophotometer (Table 10).

Table 10: Absorbance determined by UV Spectrophotometer

Fig. 7: UV estimation of Pantoprazole

8. In Vitro Dissolution Study

The results of in vitro dissolution studies are presented in Table 11.

Table 11: Dissolution time and % drug release in 0.1% HCL

Table 12: Dissolution Time And % Drug Release in Phosphate Buffer Ph 6.8

Fig. 9: Cumulative % drug release in phosphate Buffer