Formulation Development and Characterization of Mouth Dissolving Tablet Containing Omeprazole

Tablet formulations are preferred primarily because of their low Right now, pure formulations are the most important requirement, followed by increased stability, packaging, transportation, and manufacturing costs. Over the last ten years, there has been an increase in demand for evaporating tablets, and this area of the pharmaceutical industry is currently growing rapidly Super disintegrants such as croscarmellose sodium and sodium starch glycolate are used to deliver medications to living things. To get the desired result with the fewest possible side effects, the medication must be taken at work in a specific amount and concentration. Super disintegrants including sodium starch glycolate, croscarmellose sodium, and crospovidone1 are used in the two fundamental processes for making tablets for oral disintegration¹. It is also possible to lyophilize and vacuum-dry tablets to enhance their pore structure. Direct compression is utilized for all techniques because to its dependability, effectiveness, and affordability. For up to 50–60% of all dosage types, oral administration is the most common form of administration. Due to their exceptional ease of use, accuracy in Particularly popular are solid dose forms for pain relief, self-medication friendliness, dosage, and above all patient compliance. The most widely used solid dosage forms are capsules and tablets. widely used; nonetheless, swallowing issues are a major disadvantage for some patients. Drinking water is essential to taking an oral dosage form well. When traditional dose forms, such as tablets, are taken without water, people often experience discomfort.² A possible method for achieving a quick onset of action or better bioavailability for medications with a high first-pass metabolism is oral mucosal drug administration. Because a rapidly dissolving medication can enter the systemic circulation immediately through the oral mucosa, there is increasing interest in creating alternate dosage forms, such as oral fast disintegrating tablets.³

METHODS

Spectrometric analysis

In order to create a standard stock solution of 100 µg/ml, 10 mg of precisely weighed omeprazole was dissolved in 100 ml of water in a 100 ml volumetric flask. The volume was then increased to 100 ml with water. 2.5 milliliters of the standard stock solution were pipetted into a 10-milliliter volumetric flask. Water was added to get the volume up to 10 ml. Between 200 and 400 nm, the resultant solution, which contained 10 µg/ml, was scanned.⁵

Infrared spectroscopy

IR spectroscopy is helpful scientific method for determining how drugs interact chemically and polymer during storage. Therefore, infrared spectroscopy utilization to examine how additional excipients employed in the formulation interact chemically with the Omeprazole. The drug's IR spectra was compared to that physical mixture of drug and excipients to verify for any potential interactions between medicine excipients.⁴

Differential Calorimetry scanning (DSC)

The differential scanning calorimetric technique was used to do a thermal examination of omeprazole with all excipients. An device called the Shimadzu DSC-60plus was used to evaluate the samples. All excipients and a sample equal to around 8 mg of omeprazole were heated in aluminum pans from 25 to 300 °C at a rate of 10 °C per minute.⁶

Preparation of Omeprazole MDT

All materials, with the exception of Aerosil and magnesium sterate, were weighed precisely and mixed uniformly in a mortar and pestle for fifteen minutes. The prepared powder mixture was run through sieve number 60. After passing through filter number 30, Aerosil and magnesium sterate were added and combined for an additional ten minutes.⁷ 200 mg of a precisely weighed, uniformly blended powder blend was manually fed into a Cadmach tablet compression machine, which used 8 mm, breakthrough, and flat-faced punches to crush the mixture with consistent compression force and hardness. Nine formulations in all were created. ⁸.

Experimental Design

A methodical and scientific way to investigate the connection and interplay between independent and dependent variables is through experimental design. 23 In order to optimise the formulas, a complete factorial design was suggested. A sufficient degree of flexibility is provided by the chosen design to ascertain the primary impacts of both individual variables and factor interactions.¹⁰

In order to evaluate omeprazole in mouth dissolving tablets, important factors such tablet hardness, friability, disintegration time, and drug content homogeneity were evaluated. Acceptable mechanical strength and quick breakdown in the oral cavity were verified. The formulation is suitable for quick and effective oral drug administration, as evidenced by in vitro dissolution experiments showing effective drug release and UV spectrophotometric measurement at 245 nm confirming constant drug content^12-13.

In-vitro dissolution study

Dissolution studies were conducted under sink conditions using an 8-station USP Type II paddle apparatus with 900?mL of phosphate buffer (pH 6.8) as the medium. The temperature was maintained at 37?±?2?°C, with paddles rotating at 50?rpm. Samples of 5?mL were withdrawn at 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, and 12 hours, and an equal volume of fresh medium was added to maintain constant volume. The samples were diluted and analyzed using a UV spectrophotometer at 245?nm to determine drug release.^14-15

Stability Studies

Appearance

The tablets were visually inspected at regular intervals for any changes in physical characteristics such as color, texture, or surface integrity. Any signs of discoloration, mottling, or cracking were carefully noted to assess the physical stability of the formulation during storage under accelerated conditions.

Disintegration Time

The disintegration time of the tablets was determined using a standard disintegration test apparatus as per pharmacopeial guidelines. One tablet was placed in each tube of the basket rack, and the assembly was immersed in a beaker containing phosphate buffer at 37 ± 2°C. The time taken for complete disintegration of the tablets without any palpable mass was recorded.

Dissolution

The dissolution studies were performed using a USP Type II (paddle) apparatus. The tablets were placed in 900 mL of phosphate buffer (pH 6.8) maintained at 37 ± 0.5°C with paddle rotation at 50 rpm. At predetermined time intervals, samples were withdrawn and replaced with fresh medium to maintain sink conditions. The collected samples were filtered and analyzed using a UV spectrophotometer at 245 nm to determine the percentage of drug released.

Drug Content

The drug content of the tablets was assessed by dissolving a known quantity of powdered tablet in a suitable solvent such as methanol. The resulting solution was diluted to a defined volume and filtered. An aliquot was then analyzed spectrophotometrically at the specific wavelength (245 nm) to determine the actual amount of drug present in the formulation.

RESULTS AND DISCUSSION

Spectrometric analysis

The λmax of omeprazole was determined by preparing a standard solution in methanol. A 10?mg sample of omeprazole was dissolved in methanol and diluted to 100?mL to obtain a 100?µg/mL stock solution. From this, 2.5?mL was further diluted to 10?mL to obtain a 10?µg/mL solution, which was scanned in the UV range of 200–400?nm. The maximum absorbance (λmax) for omeprazole in methanol was found to be at 295?nm.

Figure No. 1: Spectrometric analysis of Omeprazole in Methanol

Standard Calibration curve

A precisely measured 10 mg dose of omeprazole was dissolved in a small amount of distilled water, and the volume was increased to 100 ml using the same solution (100 µg/ml). Subsequently, extract 0.5, 1, 1.5, 2, and 2.5 milliliters from the aforementioned solution into distinct 10-milliliter volumetric flasks, and adjust the volume to 10 milliliters to yield 1, 2, 3, 4, and 5 micrograms per milliliter, respectively. Additionally, absorbance measurements were made at 295 nm. In order to verify the calibration curve, this process was carried out three times.

Figure No. 2: Calibration Curve of Omeprazole

Drug- excipient compatibility study

Figure No. 3: FTIR Spectrum of Pure Omeprazole

Differential Scanning Calorimetry (DSC)

Figure 4 displays the results of the DSC thermograms of the pure medication and polymer, respectively

Figure No. 4: DSC Curve of Omeprazole

According to the DSC thermograms above, the melting point peak of the pure Omeprazole medication with all polymers is almost the same at 158.01 C. Consequently, it is discovered that the polymer blend does not exhibit a notable change in the DSC peak since there is no interaction with the medication, indicating satisfactory compatibility.

Figure No. 5: DSC Curve of Omeprazole – All Excipients

All values are expressed as mean± SE, n=3.

Disintegration time

The in-vitro disintegration time of the tablets was evaluated using the USP disintegration test apparatus (Electro lab). All eight formulations showed disintegration times ranging from 12?±?1.8973 to 30?±?1.8973 seconds. Formulations containing Crospovidone and Croscarmellose sodium exhibited the fastest disintegration due to their swelling, burst effect, and rapid water absorption. An increase in sodium starch glycollate and Croscarmellose sodium content further reduced disintegration time. Wetting time, measured twice for each formulation, ranged from 11?±?1.4142 to 42?±?1.8973 seconds, correlating with water absorption efficiency.

All values are expressed as mean± SE, n=3

In Vitro Drug release study

The F8 formulation was used to conduct a follow-up drug release research in phosphate buffer PH6.8. For all formulations, the percent cumulative drug release ranged from 88.27±0.5352 to 99.24±0.1401%. The higher the concentration of super disintegrants, the higher the drug release. The maximum drug release, or 99.24%, was seen in the first 15 minutes with F5 formulations.

All values are expressed as mean± SE, n=3.

Figure 6: Cumulative % drug release profile of formulation F1-F4.

Figure 7: Cumulative % drug release profile of formulation F5-F8

A polynomial equation was derived to examine the effects of independent variables on the responses, such as the percentage of drug release and the disintegration time, in order to examine the influence of three components using a complete factorial design. Regression equations are used to draw conclusions about the findings after taking into account the magnitude of the coefficient, and the sign of the coefficient shows the type of response. In a polynomial equation, a positive sign indicates that the reaction rises as the value does, whereas a negative sign indicates that the response falls as the value rises.

Figure No. 8: (A): Contour plot (B): 3D Response Surface (C): Contour plot (D): 3D Response Surface Plot

+93.31+1.82*A+1.42*B+1.96*C- 0.21*A* B-0.34*A* C+1.00* B * C+0.28*A*B*C is the drug release. This polynomial equation showed that the independent variables crospovidone, SSG, and croscarmellose sodium—had a favourable impact on drug release.

3D Response Surface Plot:

Crospovidone, SSG, and Croscarmellose Sodium's effects on the drug release time of Omeprazole were verified using a 3D response surface plot. The figure-response curve of Y1 (drug release) shows that drug release increases considerably as the concentration of Croscarmellose sodium rises from 4 mg to 8 mg, SSG rises from 4 mg to 8 mg, and Crospovidone rises from 4 mg to 8 mg.

Effect of independent factors on disintegration time (Y2)

+19.75-3.75* A-0.75* B-2.00*C-1.75%A* B-0.50*A*C-1.50*B* C+2.50 * A*B*C is the disintegration time. The independent variables, crospovidone, SSG, and croscarmellose sodium, were found to have a negative impact on disintegration time based on this polynomial equation.

3D Response Surface Plot

Croscarmellose sodium concentration rises from 4 mg to 8 mg, SSG rises from 4 mg to 8       mg, and Crospovidone rises from 4 mg to 8 mg, according to the Curve of Y2 (Disintegration Time). Figure illustrates the considerable decrease in disintegration time.  The statistical model indicates that the eighth run is an optimal formulation.  The analysis of the optimised batch's reaction, or drug release rate of 99.24% and disintegration time of 12 seconds.

Stability Studies

Research for MDTs Omeprazole tablet formulation F5, which is optimised at 40°C ± 2°C/75% RH ± 5%.