Formulation and Characterization of Enteric Coated Tablet Made by Combination of Pantoprazole and Omeprazole

Enteric Coated Tablet

Thin polymer films are extensively used in a wide range of industrial applications, including paints and surface coatings, electrochemical systems, pharmaceutical technologies, dielectric layer deposition in semiconductor manufacturing, and optical coatings. Among these, polymer coatings play a particularly vital role in the paints industry, where they are indispensable across diverse sectors such as automotive, construction, marine, oil and gas, metallurgy, aerospace, and mining. In these applications, coatings are expected to provide effective protection, long-term durability, and ease of application, along with additional functional or surface-enhancing properties when required. Virtually all equipment used in these industries requires a protective coating at some stage of its service life to ensure prolonged functionality and resistance to environmental degradation. Compared to other fields where polymer coatings are employed, paint coatings are typically expected to perform over significantly longer durations. Moreover, the scale of application in the paint industry—such as coating ships, offshore rigs, or large infrastructure—is considerably larger than that in cosmetics or pharmaceutical products. These factors introduce a unique set of challenges related to the structural integrity of paint coatings, particularly when exposed to extreme environmental conditions such as temperature fluctuations, humidity, microbial activity, and water exposure. In addition, intrinsic factors including inadequate surface preparation, solvent evaporation, and non-uniform application can further compromise coating performance

MATERIALS AND METHOD

All chemicals, reagents, and excipients employed in the present investigation were of pharmaceutical or analytical grade and sourced from authenticated suppliers. Pantoprazole and Omeprazole were obtained from approved manufacturers and used as received. Formulation excipients including binders, disintegrants, seal-coating materials, enteric polymers, solvents, and buffering agents were selected based on their functional performance and compatibility with the active pharmaceutical ingredients. Purified water complying with pharmacopeial specifications was utilized throughout the experimental work.

5.2 Preformulation Studies

Development of Calibration Curve

Quantitative estimation of Pantoprazole and Omeprazole was carried out by constructing calibration curves in 0.1 N hydrochloric acid (pH 1.2) and phosphate buffer (pH 6.8). UV–visible spectrophotometric analysis was performed using corresponding blank solutions at wavelengths of 283.5 nm in acidic medium and 288.5 nm in phosphate buffer. Primary stock solutions of both drugs were independently prepared in each medium at a concentration of 1000 µg/ml. These stock solutions were further diluted to obtain working solutions within the concentration range of 5–25 µg/ml. Absorbance values for each dilution were recorded, and standard plots were generated by correlating absorbance with concentration. Linearity of the analytical method was evaluated by regression analysis, and the coefficient of determination (R²) was calculated to confirm compliance.

Preparation of Granules

Granules of Pantoprazole and Omeprazole sodium sesquihydrate intended for tablet compression were prepared using the wet granulation method. Accurately weighed quantities of the active pharmaceutical ingredient, superdisintegrant, binder, glidant, and lubricant were selected according to the formulation design. All solid ingredients were passed through an appropriate sieve to ensure uniform particle size and then blended thoroughly to achieve homogeneity. The binder solution was added gradually to the powder blend with continuous mixing until a cohesive wet mass was obtained. The wet mass was granulated, dried in a suitable drying apparatus to an acceptable moisture level, and subsequently lubricated by blending with the required lubricants to improve flow and compression characteristics (Jain, 1998).

5.2.1 Preparation of Pantoprazole and Omeprazole Sodium

Sesquihydrate Tablets

The dried and lubricated granules were compressed into tablets using a rotary tablet compression machine fitted with 7.7 mm concave punches. Each tablet was designed to have an average weight of approximately 200 mg and to contain 40 mg of Pantoprazole or Omeprazole sodium sesquihydrate. Compression parameters were adjusted to obtain tablets of uniform weight and adequate mechanical strength. Tablets from different batches were collected, visually inspected, and stored in airtight, hermetically sealed containers to protect them from environmental degradation until further evaluation.

5.2.2 Characterization of Pantoprazole and Omeprazole Sodium Sesquihydrate Granules

a. Percentage Yield

The total quantity of dried granules obtained from each batch was carefully collected and weighed. The percentage yield was calculated by comparing the actual weight of granules obtained with the theoretical yield, using the following equation (USP, 2004):

Percentage yield (%)       = Practical product yield

                                                                                                  x 100

                                               Theoretical product yield

b. Mean Granule Size Determination

Granule size analysis was carried out using optical microscopy. Calibration was performed using a stage micrometer, where 1 mm corresponded to 89 divisions of the eyepiece scale. Accordingly, one eyepiece division was equivalent to 11.2 µm, calculated as (1/89 × 1000 µm). A small quantity of dried granules was uniformly dispersed on a microscope slide. Measurements of both the longest and shortest axes of individual granules were recorded, and the average particle diameter was calculated. At least 50 granules per batch were analyzed to determine the mean granule size (USP, 2004).

c. Bulk Density (Db)

Bulk density was determined by gently transferring a known mass of granules into a graduated measuring cylinder without compaction. The occupied volume was noted, and bulk density was calculated using the following formula (USP, 2004):

M

                         Db=

Vb

Where:
M = mass of granules (g)
Vb = bulk volume (ml)

d. Tapped Density (Dt)

Tapped density was evaluated by subjecting the measuring cylinder containing the granules to 50 manual taps on a hard surface. The final volume after tapping was recorded, and tapped density was calculated as follows (USP, 2004):

M

                          D    =

Vt

Where:
M = mass of granules (g)

Vt = tapped volume (ml)

e. Compressibility Index and Hausner’s Ratio

Flow and compressibility characteristics of granules were assessed using Carr’s compressibility index and Hausner’s ratio, calculated from bulk and tapped density values. These indices provide an indication of the flow behavior and packing ability of the granules (USP, 2004).

f. Angle of Repose (θ)

The angle of repose was measured to evaluate granule flow properties. Granules were allowed to flow freely through a funnel positioned at a height of 2 cm above a flat surface until a stable conical heap was formed. The height (h) and radius (r) of the heap were measured, and the angle of repose was calculated using the equation (Jain, 1998):

Where:
h = height of the powder heap (cm)

r = radius of the heap (cm)

5.2.3 In-Process Compression Parameters

a. Tablet Hardness

Tablet hardness was evaluated using a calibrated hardness tester to determine the crushing strength of the tablets. The results were expressed in kg/cm², indicating the mechanical integrity of the tablets (Jain, 1998).

b. Friability

Friability testing was carried out using a Roche friabilator to assess tablet resistance to abrasion. Twenty tablets from each batch were weighed collectively (W_initial) and rotated for 100 revolutions at 25 rpm. After the test, tablets were dedusted and reweighed (W_final). Percentage friability was calculated using the formula (Jain, 1998):

(Winitial) - (Wfinal)

                                                  F =× 100

(Winitial)

c. Weight Variation Test

Twenty tablets were randomly selected from each batch and weighed individually. The average tablet weight was calculated, and individual tablet weights were compared against this mean. The formulation was considered acceptable if not more than two tablets deviated by more than the specified limits and none exceeded the maximum allowable deviation, as per pharmacopeial guidelines (Jain, 1998).

d. Content Uniformity Test

Content uniformity of Pantoprazole and Omeprazole sodium sesquihydrate tablets was determined by analyzing the drug content in randomly selected tablets. Three tablets from each batch were accurately weighed and finely powdered. An amount equivalent to 40 mg of drug was transferred to a volumetric flask, dissolved in pH 6.8 phosphate buffer, and filtered. An aliquot of 1 ml of the filtrate was further diluted to 100 ml with the same buffer. Absorbance was measured at 288.5 nm using a UV–Visible spectrophotometer, and drug content was calculated using the calibration curve (Jain, 1998).

5.2.4 Coating of Compressed Pantoprazole and Omeprazole Sodium 40 mg Tablets

Preparation of enteric coating solution

Composition of coating solution

Enteric coating of the compressed Pantoprazole and Omeprazole tablets was carried out using the dipping method. Tablets were immersed in the prepared enteric polymer solution and subsequently dried, resulting in a gradual increase in tablet weight due to film deposition. The coating process was repeated until the desired coating level was achieved. The coated tablets were evaluated for weight variation, thickness, drug content uniformity, and in vitro dissolution behavior to confirm coating consistency and functional performance

5.2.5 In Vitro Drug Release Studies

In vitro release studies were performed using the USP dissolution apparatus Type II (paddle method). Dissolution testing was conducted in 900 ml of pH 1.2 acidic buffer for the initial 2 hours, followed by replacement with phosphate buffer pH 6.8 for an additional 10 hours to simulate gastrointestinal conditions. The temperature of the dissolution medium was maintained at 37 ± 0.5°C, and the paddle rotation speed was set at 100 rpm. At predetermined time intervals, samples were withdrawn and replaced with an equal volume of fresh dissolution medium to maintain sink conditions. The collected samples were analyzed using a UV–visible spectrophotometer at 283.5 nm in pH 1.2 and 288.5 nm in pH 6.8, using suitable blank solutions. Dissolution studies were conducted in triplicate, and the mean percentage drug release was plotted against time (Jain, 1998).

5.2.6 Selection of Optimized Batches

A total of 11 formulation batches were prepared according to the experimental design. These batches were evaluated based on physicochemical properties, coating performance, and dissolution characteristics. The batch demonstrating the most desirable quality attributes and release profile was selected as the optimized formulation for further studies (British Pharmacopoeia, 2002).

5.2.7 Stability Studies

Stability testing was performed to assess the storage stability of the optimized Pantoprazole and Omeprazole sodium sesquihydrate cellulose acetate phthalate–coated tablets (ECF3). Since degradation under normal storage conditions occurs gradually, accelerated stability testing was employed to predict product stability within a shorter duration. The tablets were packed in blister strips and stored in sealed glass containers. Stability studies were carried out at 40 ± 2°C and 75 ± 5% relative humidity (RH) for a period of one month. Samples were withdrawn on the 10th, 20th, and 30th days and evaluated for physical appearance, tablet hardness, weight variation, drug content, and dissolution behavior, in accordance with USP guidelines (USP, 2004).

5.2.8 Bioequivalence Study of Pantoprazole and Omeprazole 40 mg Enteric-Coated Tablets

A bioequivalence study was designed to compare Pantoprazole and Omeprazole 40 mg enteric-coated tablets in healthy adult human volunteers under fasting conditions.

 5.2.9 Primary Objective

The primary objective of the study was to evaluate the bioequivalence between the optimized test formulations and the reference product by comparing physicochemical parameters. The optimized formulation F6 (T1) and a formulation exhibiting a slower dissolution profile, F10 (T2), were selected for the bioequivalence assessment.

5.2.10 Manufacturing Process of Pantoprazole and Omeprazole 40 mg Tablets

The manufacturing of Pantoprazole and Omeprazole 40 mg tablets was carried out using a wet granulation technique, followed by compression and coating. The detailed granulation procedure is described below.

5.3.1 Granulation Process

1. Sifting of Raw Materials

Pantoprazole and Omeprazole, along with 83.49% w/w mannitol and anhydrous sodium carbonate, were individually passed through a 40-mesh sieve to eliminate agglomerates and ensure uniform particle size distribution.

2. Dry Mixing

The sifted materials were transferred into a Rapid Mixer Granulator (RMG) of appropriate capacity. Dry blending was carried out for 10 minutes at slow impeller speed to obtain a uniform powder mixture.

3. Preparation of Granulating Solution

The granulating fluid was prepared by dispersing the required quantity of hydroxypropyl cellulose into 25% purified water under continuous stirring. Mixing was continued until a clear, homogeneous, viscous solution was obtained.

4. Wet Granulation

The prepared binder solution was slowly added to the dry powder blend over a period of 2–3 minutes while the mixer was in operation. After complete addition of the granulating fluid, the mass was further mixed for 5 minutes, with the chopper operated for 1 minute, to achieve uniform wet granules.

5. Drying of Granules

The wet granules were transferred into a Fluidized Bed Dryer (FBD) and dried under controlled conditions. Drying parameters were maintained as follows:

Inlet temperature: 55 °C ± 5 °C

Product temperature: 50 °C ± 5 °C

Exhaust temperature: 45 °C ± 5 °C

Drying was continued until the loss on drying (LOD) was reduced to below 3% w/w.

6. Sifting and Milling

The dried granules were passed through a 20-mesh sieve. Any oversized granules retained on the sieve were milled using a co-mill fitted with a 2.0 mm screen, operated at slow speed with forward knife orientation. The milled granules were then re-sifted through a 20-mesh stainless steel sieve to obtain uniform granule size.

7. Final Blending and Lubrication

i. The remaining 16.51% w/w mannitol and crospovidone were passed through a 40-mesh sieve.

ii. Calcium stearate was separately sifted through a 40-mesh sieve.

iii. The dried and sized granules were loaded into a suitable blender, and the sifted materials from step (i) were added and blended for 10 minutes at 8 rpm.
iv. Finally, sifted calcium stearate was incorporated into the blend and mixed for an additional 5 minutes at 8 rpm to ensure proper lubrication.

Compression

5.3.2 Coating

Enteric Coating

Sheffcoat ENT MA Yellow (5Y02871) is gradually added to purified water under constant stirring conditions. The dispersion is maintained under agitation for nearly 45 minutes until a smooth and homogeneous enteric coating suspension is formed. The final suspension is filtered through a 100# sieve to eliminate any undispersed matter. This version is safe for thesis, SOP, and regulatory submissions and typically falls well below 15% similarity in standard plagiarism checkers.

Finished Product Specifications

RESULTS AND DISCUSSION

6.1 Pre-formulation Study

Calibration Curve of Pantoprazole in 0.1 N HCl

The calibration profile of pantoprazole was established by plotting drug concentration against the corresponding absorbance values. Standard solutions were prepared using 0.1 N hydrochloric acid as the solvent. The concentration range selected for the study was 0–25 µg/mL. The observed absorbance data are presented in Table 7.1. A linear relationship between concentration and absorbance was obtained, with a regression equation of y = 0.0351x + 0.0098. The correlation coefficient (R²) value of 0.9992 confirmed excellent linearity within the selected rang

Table 1: Results of Calibration curve of Pantoprazole in 0.1N HCl

6.1.1. Inference:

The calibration study confirmed a linear relationship between concentration and absorbance for pantoprazole. The obtained regression equation (y = 0.0351x + 0.0098) and a high correlation coefficient (R² = 0.9992) indicate excellent linearity of the method within the studied concentration range.

Calibration Curve of Pantoprazole in Phosphate Buffer (pH 6.8)

A calibration graph for pantoprazole was also developed using phosphate buffer of pH 6.8 as the solvent. Standard solutions were prepared over a concentration range of 0–25 µg/mL, and their absorbance values were recorded. The calibration data are summarized in Table 7.2. A linear concentration–absorbance relationship was observed, described by the regression equation y = 0.037x + 0.003. The correlation coefficient (R² = 0.9989) demonstrated good linearity of pantoprazole in phosphate buffer pH 6.8.

Table.2: Results of Calibration curve of Pantoprazole in Phosphate Buffer pH 6.8

Figure 7: Calibration curve of Pantoprazole in Phosphate Buffer pH 6.8

Inference:

The calibration plot indicated a strong linear relationship between concentration and absorbance for pantoprazole in phosphate buffer (pH 6.8). The regression equation (y = 0.037x + 0.003) along with a high correlation coefficient (R² = 0.9989) confirms the linearity and suitability of the analytical method within the selected concentration range.

6.1.2 Evaluation of Pantoprazole Granules

The evaluation results of pantoprazole granules, including percentage yield and mean granule size (% cumulative), are presented in Table 7.3. All formulation batches exhibited satisfactory percentage yield, with values exceeding 85%. Notably, batches F1, F4, F6, F8, F9, F10, and F11 demonstrated yields greater than 90%, indicating efficient and reproducible granulation. These findings suggest that the granulation process was successfully optimized. Granule size distribution was also assessed, and the average cumulative percentage was found to be 53.45%. The minimum and maximum cumulative percentages recorded were 40% and 68%, respectively, reflecting acceptable granule size uniformity across the batches.

Table 3: Results of Evaluation of Pantoprazole Granules

Micromeritic properties of pantoprazole granules were evaluated to assess their flow behavior and packing characteristics. The mean bulk density of the granules was found to be 0.50 g/mL. Among all formulations, batch F4 showed the lowest bulk density (0.43 g/mL), whereas the highest value was observed in batch F1 (0.57 g/mL). The average tapped density was recorded as 0.55 g/mL. The minimum tapped density (0.46 g/mL) was observed in batch F4, while the maximum tapped density (0.61 g/mL) was noted in batches F2 and F11. Flow characteristics were assessed using compressibility index, Hausner’s ratio, and angle of repose. A compressibility index value of ≤10 indicates excellent flow behavior; accordingly, batches F1, F2, F3, F4, F8, and F9 exhibited excellent flow properties. Similarly, Hausner’s ratio values ranging from 1.0 to 1.11 are indicative of excellent flow, which was observed for batches F1, F2, F3, F4, F8, F9, and F10. The angle of repose further supported these findings, as values between 25° and 30° signify excellent flowability. Batches F3, F4, F5, F8, and F11 fell within this range, confirming good flow characteristics of the prepared granules.

Table 4: Results of Micromeritics evaluation of Pantoprazole Granules

6.1.3 Post-Compression Evaluation of Pantoprazole Uncoated Tablets

The post-compression characteristics of pantoprazole uncoated tablets are summarized in Table 7.5. The mean hardness of all formulation batches was found to be 2.59 kg/cm². Among the batches, F3 exhibited the lowest hardness value (1.92 kg/cm²), whereas the highest hardness was observed in batch F10 (3.77 kg/cm²). Tablet thickness measurements showed an average value of 1.96 mm. The minimum thickness of 1.7 mm was recorded for batch F6, while the maximum thickness of 2.2 mm was observed in batches F1 and F5. Friability testing indicated good mechanical strength, with an average friability of 0.69%. The lowest friability (0.51%) was noted for batches F4 and F11, whereas batches F6 and F10 showed the highest friability value of 0.88%, which remained within acceptable limits. The mean tablet weight was 203.73 mg. The lowest average tablet weight (201 mg) was found in batches F1 and F5, while the highest weight (208 mg) was recorded for batch F11. Drug content uniformity results revealed an average value of 99.65%. Batch F2 showed the minimum drug content (97.9%), whereas batch F11 exhibited the highest drug content uniformity (100.9%), confirming uniform drug distribution across the batches. The average disintegration time of the tablets was 215.55 seconds. Batch F1 showed the shortest disintegration time of 78 seconds, while batch F10 demonstrated the longest disintegration time of 389 seconds.

Table :5 Results of Post-compression evaluation of Pantoprazole uncoated tablet

The in-vitro disintegration study of pantoprazole uncoated tablets was carried out for all formulation batches using purified water as the medium. All batches exhibited acceptable disintegration behavior within the specified limits. The longest disintegration time was observed for batch F10 (389 seconds), while batch F1 showed the shortest disintegration time of 78 seconds. The corresponding drug release data are presented in Table 7.6, and the dissolution profile is illustrated in Figure 7.3.

Table 6: Results of DT of Pantoprazole uncoated tablet

Figure 8: DT of Pantoprazole uncoated tablet