Formulation and Evaluation of Omeprazole Floating Tablet for The Treatment of Peptic Ulcer

A floating tablet represents a form of gastroretentive drug delivery system (GRDDS) engineered to stay afloat within the gastric environment for prolonged periods. This extended buoyancy facilitates sustained drug release and enhances gastric retention time. The tablet achieves floatation either through the incorporation of low-density polymers or by utilizing gas-generating agents that react upon contact with gastric fluids, ensuring that the dosage form remains suspended in the stomach.¹ Omeprazole, a proton pump inhibitor that stops the stomach from creating gastric acid, is often taken as a regular tablet at a dose of 15 mg. Omeprazole has a low water solubility and is chemically labile in an acid environment. Omeprazole has a biological half-life of 1 to 1.2 hours.²

MATERIALS AND METHODS

Omeprazole and Microcrystalline cellulose PH 102 was obtained as gift sample from Murli krishna Pharma Pvt. Lit. Ranjangoan, HPMC K 4 M, HPMC K 15 M, PVP K 30, was obtained from Sharadchandra Pawar College of Pharmacy Dumbarwadi, Otur, Pune, Maharastra, India- 412409. Sodium Bicarbonate, Citric Acid, Magnesium stearate, Talc was obtained from Delight College of Pharmacy, Koregaon Bhima, Pune, Maharastra, India- 412216.

Preparation of Omeprazole Tablet

Step 1: Solution Preparation

Dissolved Required Quantity of PVP K30 and Omeprazole API completely in water to make a clear solution by using mechanical stirrer.

Step 2: Dry Mixing

Sodium bicarbonate, Citric acid, Magnesium stearate, Talc, MCC PH 102 (Microcrystalline Cellulose), HPMC K4M, HPMC K15M are pass through the mesh no.24 and mix in the bowl for dry mixing purpose.

Step 3: Preparation of Drug and Excipient Damp Mass

Drug solution which is directly added into the Dry mixture in Rapid mixture Granulator and prepare damp mass by using required quantity of purified water. Mix well until a damp mass is formed (the mixture should hold together when pressed but should not be too wet).

Step 4: Wet Sieving

Pass the damp mass through sieve no. #24 to form uniform granules.

Step 5: Drying

Dry the wet granules properly in Tray Dryer to remove moisture content from Drug granules

Step 6: Compression

Compress the dried granules into tablets using a single tablet compression machine.

Step 7: Coating

Coat the compressed tablets by using film coating solution (HPMC and Isopropyl Alcohol) to achieve uniform layer of tablet.

Figure 1: Omeprazole Floating Tablet

Table 1: Formulation of Omeprazole Tablet

Preformulation studies:

1. Physical appearance:

Omeprazole was analysed for colour, odour and texture. The data is ported in table 2.

2. Meiting point determination:

The melting point of the drug was determined using the capillary fusion method. A small quantity of the drug was packed and sealed in a glass capillary tube, which was then placed in an inverted position within the melting point apparatus. The temperature at which the drug melted was recorded and compared with its reported literature value. The results are presented in Table 2.³

3. Solubility Analysis:

The solubility of the drug was assessed by placing a small quantity of the sample in separate test tubes containing various solvents including distilled water, ethanol, and methanol. The extent of dissolution was visually examined to determine the drug’s solubility profile. This test helps evaluate the drug’s affinity for different solvents, providing essential insights for formulation development and dosage form design.⁴

Table 2: Parameters and Observation of omeprazole

4. Determination of Absorbance Maxima:

Omeprazole was quantitatively analysed using a UV spectrophotometer with methanol solution. A standard calibration curve was established by preparing a stock solution with a concentration of 1000µg/mL in methanol. Test solutions were then prepared by diluting the sample to concentration of 2,4,6,8 and 10 µg/mL and their absorbance was measured at the max of 301 nm. The plot of absorbance v/s concentration (µg/mL) was plotted and data was subjected to weighed linear regression analysis in Microsoft excel.⁵

Table 3: Calibration curve of Omeprazole

Figure 2: Calibration Curve of Omeprazole

EVALUATION OF OMEPRAZOLE TABLET

1. Pre-compression Parameter

1.  Angle of repose

A powder is allowed to pass through a funnel and land freely on a surface to calculate the angle of repose. When the pile comes into contact with the funnel's tip, further powder is not added. Without upsetting the pile, a circle is drawn around it. Table 4 displays the measurements for the height and diameter of the resultant cone. After three iterations of the same process, the average value is calculated. This formula is used to determine the angle of repose.⁶

θ = Tan^-1 h/r

Where, θ = Angle of repose,

h = height of the powder cone,

r = radius of the powder.

2. Bulk Density:

Disassemble any agglomerates that could have developed during storage and add around 100g of the test sample (M), weighed with an accuracy of 0.1%, to a dry 250 ml cylinder without compacting. Technique II, Choose a sample mass with a 150–250 ml untapped apparent volume. For apparent quantities between 50 and 100 ml, a 100 ml cylinder is utilized. Carefully fill the cylinder. If required, carefully level the powder without compacting it. Then, as indicated in Table 4, read the unsettled apparent volume (Vo). Utilizing the following formula, get the bulk density in g/ml:⁷

Bulk density (BD) = M/Vb

Where, BD = Bulk Density,

M = Mass of the powder,

Vb = Bulk Volume of the powder.

3. Tapped Density:

A measuring cylinder was filled with a precisely weighed 1.25gm of powder. Using an appropriate mechanically tapped density tester, mechanically tap the sample-containing cylinder by elevating it and letting it fall under its own weight at a notional rate of 300 drops per minute. Measure the tapped volume (Va) after 500 taps of the cylinder. Measure the tapped volume as (Vb) after repeating the process for 750 more tapping sands. as seen in Table 4. Repeating the tapings 1,250 times was necessary since the difference between Va and Vb was greater. The tapped density was then determined using formula⁸

Tapped density (TD) = M/Vt

Where, TD = Tapped Density,

M = Mass of the powder,

Vt = Tapped volume.

4. Carr's index:

As seen in Table 4, the compressibility index of granules may be calculated using Carr's index, which was calculated using the following formula:⁹

Carr's index (%) = (Tapped density – Bulk density) / Tapped density * 100.

5. Hausner Ratio:

Hausner ratio (HR) is used to predict the flow of the powders. It is computed by the following equation:

HR = Pt/P

where, pt = tapped density,

pb = bulk density.

Hausner ratio less than 1.25 is a good indicator of flow properties.

Post compression parameters:

1.  Friability and hardness:

A Monsanto Hardness Tester was used to measure the tablet's hardness. From each batch, ten tablets were chosen at random and their hardness was examined. Additionally, the mean and standard deviation were computed. Roche Friabilator conducted the friability test. By using a plastic container that rotates at 25 rpm and drops the tablets six inches apart with each rotation, ten weighted tablets were exposed to the combined effects of attrition and shock. The tablets were de-dusted and reweighed every 100 rotations. Table 5 illustrates the calculation of the % friability.¹⁰

Figure 4: Fraibility tester

2. Weight variation:

Ten 200 mg tablets were chosen at random from each batch, and each tablet's weight was measured separately before the average was determined and compared to the individual tablet weight. As seen in Table 5, the % weight difference was computed from this and subsequently verified for USP requirements.¹¹

3. In vitro buoyancy studies

The floating lag time was used to calculate the in vitro buoyancy. A 250 ml beaker with 200 ml of 0.1 N HCI was filled with the tablets. Floating Lag Time (FLT) is the amount of time needed for the tablet to rise to the surface and float, and Total Floating Time (TFT) is the amount of time the tablet stayed buoyant, as indicated in Table 6.

4. In Vitro Dissolution Study¹²

The USP type I dissolving equipment was used to conduct an in vitro drug release evaluation of floating tablets. To stop the tablet from escaping to the release medium, a piece of muslin fabric was placed over the baskets. In the dissolving investigation, a tablet containing 10 mg of Omeprazole was utilized. The test was conducted in 0.1N HCI (900 ml) with stirring at 50 rpm and maintained at 37+0.5°C. At regular intervals, 10 ml of the sample was taken out, and the same volume of brand-new dissolving liquid was added to the dissolution vessel. The absorbance of the gathered aliquots was measured spectrophotometrically at 300 nm, respectively. Calculations were made using calibration curves created in the corresponding media concentrations. The correction factor was used in accordance with the equation below to account for the loss of medication in the aliquot substituted.

RESULT AND DISCUSSION

Preformulation parameters:

The main factor for determining the material's suitability for the formulation was its precompression characteristics. When choosing any material for dosage form formulation, it was crucial to know the bulk density, tapped density, Carr's index, Hausner's ratio, and angle of repose because the goal was to use the direct compression method for tablet formulation. The assessed characteristics of bulk density, tapped density, Carr's index, Hausner's ratio, and angle of repose for different tablet formulations are shown in Table 4. The evaluation parameters' results indicate that it is appropriate to use as the preferred formulation material.

Table 4.  Evaluation of preformulation parameters

Post compression parameter:

All formulations of tablets maintained a smooth, flat-faced circular shape that is off-white in color. The tablets' hardness was assessed using a Monsanto tester, yielding values ranging from 4.3 to 4.6 kg/cm². Using a friabilator, friability was assessed and determined to be 0.38 to 0.52. This suggests that the tablets have a satisfactory level of mechanical resistance. The estimations of drug content yielded values between 90.56% to 96.33%, indicating a high degree of uniformity in drug content across various formulations. The % weight variation of all the tablets was within the Pharmacopoeial limits, so they all passed the weight variation test. The outcomes are displayed in Table 5.

Table 5: Evaluation of Post Compression Parameters

Table 6: Batch Buoyancy Lag Total Floating

The USP dissolving equipment 2 (paddle) was used to conduct dissolution investigations on the floating formulations F1 through F6 in 900 milliliters of 0.1N HCl medium. The bubbling floating tablet of as indicated in Table 7, omeprozole was prepared in 6 distinct batches, A through F, utilizing the hydrophilic polymers HPMC K 4 M and HPMC K 15 M in addition to the effervescing agents sodium bicarbonate and citric acid. 30% of the drug was released in the first two hours, and 94% of the drug was released in the next seven hours, respectively (table 7). The release rate was raised in the following order among these formulas: F > A > B > C> E > D. In 7 hours, 94% of the medication was discharged.  Therefore, it may be said that Omeprazole's effervescent floating tablet provided a gradual and thorough drug release distributed over 7 hours.

Table 7: Cumulative % drug released of A to F (0.1N HCl) Formulation

Figure 5: In vitro drug release