INTRODUCTION:

Medication can be constantly and repeatedly injected into the upper gastrointestinal tract using gastro-retentive drug delivery devices, which hold the medication in the abdomen for a longer period of time prior to its active constituents are released¹^,².

Modified release drug delivery systems with prolonged periods of stomach residence, stomach-localized medications, an absorption window in the upper part of the small intestine or stomach, instability in the intestinal or colonic environments, or low solubility at high pH levels are among the most captivating³. Because they stay buoyant in the stomach for a longer amount of time without slowing down the rate of gastric emptying, floating medication delivery systems have a lower bulk density than gastric fluids⁴. Oral drug administration is the most convenient and widely used approach. Recent developments in controlled drug delivery formulations and the polymers used in these systems allow them to serve purposes beyond simply prolonging the medication's release duration. They are made to disperse the active ingredient in the medication in a steady and gradual manner over the course of 12 to 24hours. Because of their greater rates of patient compliance, more convenient delivery of pharmaceuticals, decreased side effects, and increased dependability, they are more effective in treating chronic illness conditions. The technique of appropriately coupling a natural or synthetic polymer with a medication or other active ingredient to distribute the active medication in a predetermined manner is termed as “controlled drug delivery.” Notwithstanding their benefits, these products have a number of drawbacks, including reduced absorption, potential toxicity, and the generation of unwanted by products for the length of the intended use. In this, the floating system is a widely utilized technique. Usually, the non-effervescent methodology was employed for creating floating systems⁵. When hydroxyethyl cellulose (also known as hydroxypropyl methylcellulose, or HPMC) is dissolved in water, a colloid solution is produced. It’s a viscoelastic, inert, semi-synthetic polymer. It serves as a coating polymer, bioadhesive, thickening agent, enhancer of solubility in solid dispersions, binder in the granulation process, and in formulations with modified release. It is frequently employed as a delivery element in oral pharmaceutical solutions to provide controlled release of a medication, extending its half-life and enhancing its therapeutic effects⁶. A protein pump inhibitor (PPI), pantoprazole, is advised for the treatment of acute benign gastric ulcers, acute duodenal ulcers, GERD, and as a prophylactic against duodenal ulcers. It inhibits the enzyme competitively and has a localized impact on the stomach. H+/K+ ATP is present in the parietal cells of the stomach⁷.

Floating system:

Floating delivery systems for pharmaceuticals (FDDS) float in the stomach without slowing down the rate of gastric emptying since their bulk density is lower than that of gastric fluids. As the body floats on the contents of the stomach, the medication reaches the body at the proper rate. The drug releases and the stomach's residual system is emptied⁸.

MATERIALS AND METHODS:

Determination of λ max of Pantoprazole:

Pantoprazole (10mg) was accurately weighed out and dissolved in 100ml of 0.1N HCL. Stock solution with a concentration of 100g/ml was produced. The concentration (10g/ml) solution of Pantoprazole was made using an aliquot of 1ml from the stock solution, Using a UV spectrophotometer and 0.1N HCL, the absorbance of the solution was determined⁹.

Preparation of Standard Calibration Curve of Pantoprazole:

Preparation of stock solution:

10mg of accurately weighed pantoprazole were dissolved in 0.1 N HCL in a 100ml volumetric flask to produce a standard stock solution with a concentration of 100g/ml. This is the standard stock drug.

Preparation of standard calibration curve:

Pipetted into a 10ml volumetric flask, 0.5, 1.0, 1.5, 2.0, and 2.5ml of the 100g/ml solution supplied the 5–25 g/ml concentration needed for the standard calibration curve. The remaining volume was filled with 0.1N HCL. Each solution's absorbance was measured at its maximum wavelength. The sample was scanned in a UV Spectrophotometer between 200 and 400nm against a blank solution of 0.1N HCL in order to determine the wavelength at which the solution's greatest absorption occurred¹⁰.

Drug Polymer Interaction by FTIR:

IR spectroscopy is useful analytical technique to the characterization of drug. Therefore, infrared spectroscopy is used. The powder mixture of Pantoprazole and HPMC K4M are mixed in ratio (1:1) the same method was applied for other mixture. Then a small fraction of Using an FTIR Spectrophotometer, The pellet's wavelength range of 4000-400 cm-1 has been reported¹¹.

Preparation of Pantoprazole floating tablet:

The direct compression technology has been used in the current quest to create floating tablets. Pantoprazole, sodium bicarbonate, citric acid, microcrystalline cellulose, and HPMC K4M were all precisely measured out, sieved through sieve number 60, and then uniformly blended using a mortar and pestle. Using a Rotary tablet punch machine, the powder was compacted into tablets after being lubricated with talc and magnesium stearate. The formulation batches are shown in Table I and formulated tablets are shown in Fig 1.

Table I: Formulation table of Pantoprazole floating tablet

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8
Pantoprazole	40	40	40	40	40	40	40	40
HPMC K4M	40	80	120	-	-	-	80	40
Ethyl cellulose	40	40	40	40	40	40	20	20
β-cyclodextrin	-	-	-	40	80	120	40	80
MCC	80	40	20	80	40	20	20	20
Citric acid	20	20	20	20	20	20	20	20
Na HCO3	20	20	10	20	20	10	20	20
Talc	5	5	5	5	5	5	5	5
Mg. stearate	5	5	5	5	5	5	5	5
Total weight. (mg)	250	250	250	250	250	250	250	250

Fig 1: Formulated Pantoprazole floating tablets

Pre-compression evaluation of Pantoprazole floating tablet:

Angle of repose:

The angle of repose is estimated via the funnel method. The resulting mixing is put into a funnel after been properly weighed. The funnel's height has been chosen such that the funnel's tip just touches the top of the mix heap. The medicinal product and excipient mixture were allowed to freely pass through the aperture and land on the surface. The following formula was used to determine the angle of repose once the powder cone's diameter was evaluated:

Tan Ө = Height/Radius

In this scenario, H stands for height, R for radius, and Δ for putting forward. The substance is flowing without difficulty if the angle of repose is less than thirty degrees ¹².

Table II: Relation between angle of repose and flow property

Angle of repose	Flow
< 25	Excellent
25 - 30	Good
30 - 40	Passable
> 40	Very poor

Bulk density:

Bulk density is calculated by dividing the mass of the powdered material by its volume. The powder's bulk density is primarily influenced by the particle size distribution, shape, and inclination toward joining together of the particles. A weighted portion of the combine is placed into a measuring cylinder, and the volume and weight are taken into account to calculate the apparent density.

This formula may be used to determine bulk density:

Bulk volume/total mass equals bulk density.

Tapped density:

A cylinder for measuring that holds a certain mass of the healthcare excipient combine is set up to make the measurement. The mass of the tablet blend that equals the tablet's tapped volume is identified as the tablet's "tapped density". The height is measured after a carefully weighed amount of the tablet combination has been added into the cylinder used for measurement. Then, the cylinder was allowed to tap 100 times upon a hard surface while carrying its own weight. The tapping stopped as soon as the change in height ceased. The following formula can be used to get the tapped density.

Tapped Density = Total mass/Tapped Volume

Hausner’s ratio:

A measure of how easily powder flows is the Hausner's ratio. The ratio of the tapped density compared to total density illustrates the flow characteristics of powder. The provided formula was used to obtain Hausner's ratio:

Hausner’s ratio = Tapped density/Bulk density

Where, Lower Hausner’s ratio that (<1.25) indicates superior flow characteristics than higher ones. Poor flow indicated by (>1.25)¹³.

Table III: Grading of the powders for their flow properties according to Hausners ratio

Hausners Ratio	Flow
1.00-1.11	Excellent
1.12-1.18	Good
1.19-1.25	Fair
1.26-1.34	Passable
1.35-1.45	Poor
1.46-1.59	Very Poor
More than 1.60	Very, Very Poor

Carr’s compressibility index:

The ability of a combination to decrease in volume when compressed using bulk density and the tapped density is known as compressibility. The Carr's compressibility index, which measures the blend's compressibility, was determined. The relative flow rate is indirectly connected to this. The provided formula determines the compressibility index:

Tapped density – Bulk density

Compressibility Index (%) = ------------------------- × 100

Tapped density

Post- compression evaluation:

Weight uniformity:

We weighted 20 tablets at random from each batch. The average weight was calculated, followed by the individual measurements of weight of each tablet. Then, the weights of the different tablets were contrasted with the average. The weight of each pill was tested to see whether or not there had been any variation from the average weight. This test demonstrates the need for uniformity in weight throughout the board for all tablets in a given batch. If there is any weight variation, it ought to stay within the I.P limitations. If no more than two of the twenty pills used for the test fall beyond the I.P. limits, the test was considered accurate.

Hardness:

The weight of each tablet was weighed individually and then the average weight was determined. The weights of the various tablets were then assessed against the average. It is expressed as kg/cm^2. The device that needs to be tested is put on the hardness tester's surface, and the display readout indicating what amount of pressure is needed to break the tablet in kilograms is noted. The weight of the material used, the separation between both of the punches during compression, and the pressure utilized during compression all affect how hard a tablet is.

Friability:

When exposed to mechanical shock or attrition, it is an instance where tablet surfaces become damaged and/or exhibit indications of lamination or fractures. The USP EF 2 friabilator from Electro Lab was used for evaluating the tablets' friability. It's stated as a percentage (%). Ten pills were placed into the friabilator after being originally weighed (W Initial). For 4 minutes, the friabilator was run at 25 rpm. The medication was once more weighed (W final).

Next, the percentage of friability was calculated by,

Intital weight – Final weight

Friability = ------------------------------------ × 100

Intital weight

Weight variation:

To verify for weight variance, the pills were randomly chosen from each formulation and weighed separately. The U.S. Pharmacopoeia permits a slight variance in tablet weight. The permitted weight fluctuation is as follows in %.

Table IV: Percent deviation in weight variation

Average weight of tablet	Percent deviation
80 mg or less	± 10%
80 mg – 250 mg	± 7.5%
250 mg or more	± 5%

Percentage Assay:

The five tablets in each formulation are weighed before being ground up and mixed in a mortar. 10mg of the material were thereafter added to the 100ml volumetric flask. Using the drug's standard calibration curve, the concentration of pantoprazole in ug/ml was ascertained. Following the drug's dissolution in the solvent (0.1N HCL), the solution was filtered, and 1milliliter of the filtrate was added to a 50 milliliter volumetric flask and diluted with 0.1N HCL to reach the 50 milliliter mark. This was the stock solution; 1ml was taken out and added to a 10ml volumetric flask. The volume was then increased to 10ml using 0.1 N HCL as the solvent, and it was spectrophotometrically measured at 290nm ¹⁴.

Assay was calculated by using the formula:

Absorbance of Sample

% Assay = ----------------------------------- × 100

Ansprnamce of Standard

Determination of Floating Lag Time (Buoyancy Study):

As the tablet rises from the bottom of the dissolution flask to the top, that is known as the floating lag time. A dissolution test apparatus USP (Type II) holding 900 ml of 0.1N HCL at 37±0.5°C was used to measure the floating lag time of the tablet.

Determination of Duration of Floating (In-Vitro Floating Time)

The length of time that the formulation remains suspended on the medium's surface is referred to as the floating duration. A dissolution test device USP (Type II) with 900 cc of 0.1 N HCL at 50 rpm and 37±0.5°C was used to measure how long the tablets floated¹⁵.

Swelling Index:

The polymers' capacity to absorb water and expand can be used to gauge how much they are swelling. Studying the formulation's water absorption, USP Dissolve Apparatus II was employed. 0.1 N HCL (900ml) was the medium used in the examination; it was spun at 50rpm and kept at 37±0.5⁰C. The formulation is removed, blotted to remove excess water, and weighed after a predetermined amount of time. The following formula is used to calculate the tablets' swelling characteristics when stated in terms of water uptake (WU)¹⁶.

Swellon weight – Intial weight

WU % = --------------------------------------- × 100

Initial weight

In- Vitro Dissolution Studies:

Studies on dissolution were carried out in a sink environment. A standardized 8 station dissolving test equipment with paddles (USP equipment Type II) and 900 ml of a solvent with 0.1 N HCL (pH 1.2) as a medium were used to conduct the dissolution experiments on the produced tablet. Throughout the experiment, the temperature was held constant at 37±2 ^oC while the paddles were spinning at 50rpm. 5ml samples were taken at intervals of 0.5,1, 1.5, 2, 3, 5, 6, 7, 8, 9, 10, 11, and 12 hours according to the dissolution data base. To keep the volume constant throughout the experiment, an equivalent volume of the dissolving media was changed. Samples were taken out, diluted, and the quantity of drug release was calculated using an UV spectrophotometer that operates at 290nm^17,18.

Mathematical Modelling of Drug Release Profile:

Researchers were able to look into the drug release from the Pantoprazole floating tablets by using the Higuchi equation, zero order, and first order kinetics analysis of the release data. The release process became recognised by adapting Korsmeyer Peppas' model to the data¹⁹.

a) Zero Order Kinetics:

When expressed as cumulative percent drug release vs time, the data exhibits zero-order release kinetics with a slope equal to K0.

The following equation would predict a zero-order release:

At =A0-K0t

Where, At= Drug release at time, A0= Initial drug concentration, K0=Zero-order rate constant (hr-1).

b) First Order Kinetics:

A straight-line result from plotting the data as log cumulative% medication remaining vs time, showing that the release of medication followed first order kinetics. You may get the constant K by multiplying the slope values by 2.303.

First order release would be predicted by the following equation:

Log C = log C0 – Kt / 2.303

Where, C = Amount of drug remained at time t, C0 = Initial concentration of drug, K = First-order rate constant (hr-1).

c) Higuchi’s Model:

Plotting the data as cumulative drug release vs. square root of time produced a straight line, indicating showed that the drug was released through a diffusion process. Higuchi's 1963 work reveals that the slope is K. Drug release from the formulation by diffusion has been described by following Higuchi’s classical diffusion equation:

Q = [Dε / ε (2A - εCS) CSt]1/2

Where, Q = Amount of drug released at time t, D = Diffusion co-efficient of the drug in the floating tablet,

A = Total amount of drug in unit volume of floating tablet, CS = Solubility of the drug in the floating tablet,

ε = Porosity of the floating tablet, t = Tortuosity

d) Korsmeyer Equation/ Peppa’s Model:

When the drug release log is graphed against time, a straight path with a slope of n is produced, from which the y-intercept can be used to compute the K. To examine the mechanism of drug release, the release data was fitted to the well-known exponential equation (also referred to as the Korsmeyer equation or Peppa's law equation), which is commonly used to characterise the behaviour of drug release from polymeric systems.

Mt / Ma = Ktn

where K = Constant combining the geometrical and structural properties of the drug/polymer, n = Diffusion exponent linked to the release mechanism, and Mt/Ma = the fraction of drug released at time t.

Applying log to both sides of the equation above reduces it to: Log Mt/Ma = Log K+n log t

While n varies between 0.5 and 1.0 for anomalous (non-Fickian) transport, n = 0.5 for Fickian release.

Table V: Mechanism of drug release as per Korsmeyer equation/ Peppa’s model

Sr. No	‘n’ Value	Drug release mechanism	Rate as a function of time
1	0.45	Fickian release	t -0.5
2	0.45<n =0.89	Non- Fickian transport	t n-1
3	0.89	Class II transport	Zero order release
4	Higher than 0.89	Super case II transport	t n-1

Comparative Study with Marketed Preparation:

A comparison study will be conducted by using dissolution analysis between optimize formulation and marketed formulation. A modified USP XXIV dissolving device type II (paddle) was used to evaluate the in-vitro dissolution of drugs from the tablets. The cumulative drug release (%) was calculated utilizing a standard curve.

RESULT AND DISCUSSION:

Determination of λ max of Pantoprazole:

Through the assistance of a UV-visible spectrophotometer, the λ max of pantoprazole in 0.1N HCL was determined to be 290nm. (As depicted in fig. 2)

Preparation of standard calibration curve

The Pantoprazole calibration curve was done in 0.1 N HCL. The absorbance of the solution at 290nm was measured using a UV-visible spectrophotometer. Table VI provides the absorbance at different concentrations, and Figure 3 shows the Pantoprazole calibration curve in 0.1 N HCL.

Fig 2: λ max of Pantoprazole in 0.1 N HCL

Table VI: Concentration and absorbance in 0.1 N HCL

Sr. No.	Concentration (µg/ml)	Absorbance
1	5	0.164±0.005
2	10	0.271±0.003
3	15	0.411±0.002
4	20	0.596±0.001
5	25	0.711±0.004

Fig 3: Calibration curve of Pantoprazole in 0.1N HCL

Drug Polymer Interaction by FTIR

The goal of the FTIR investigation was to assess whether the medicine Pantoprazole and the polymers HPMC K4M, Beta cyclodextrin, and other kinds of polymers could interact. Pantoprazole's FTIR revealed the peaks at 3411.42, 3387.43, 2358.21, 1586.64, 1363.47, and 1032.95 nm, which are attributed to the functional groups N-H, O-H, CH3, C-O, C-F, and S=O, as depicted in figures 4,5, 6, and 7.

Fig 4: FTIR Spectra of Pantoprazole

Fig 5: FTIR spectra of Pantoprazole + HPMC K4M

Fig 6: FTIR spectra of Pantoprazole + beta cyclodextrin

Fig 7: FTIR spectra of Pantoprazole + All excipients

Pre-compression evaluation of Pantoprazole floating tablet

The bulk densities for all formulations were between 0.33 and 0.42grams/ml, while the tap densities were between 0.40 and 0.49grams/ml. All of the formulations' angles of repose fell between 22.29° and 27.11°, which is in the outstanding or good range and indicates the outstanding flowability required for optimum particle flow. The range of values of 11.62 to 17.5% for the powder blend's Carr's index was determined to be excellent or within acceptable bounds, indicating good or reasonable flowability for the correct flow of powder mix. The Hausners ratios was discovered to be between 1.13 and 1.21. All of these outcomes are suggested in Table VII.

Post compression evaluation for Pantoprazole floating tablet:

The weight variance for all formulations was between 244 and 248mg, while the diameter variation was between 10.00mm. All of the formulas' tablet thicknesses were determined to be between 4.1 and 5.0 mm, which is a respectable range. The hardness of the tablets was discovered to be good or in the acceptable range for all formulations at a value of 4.7 to 5.4 kg/cm2. The range of friability was found to be 0.21 to 0.85%. Table VIII suggests all of these results, and Fig. 8 presents floating tablet graphics.

Swelling Index of Pantoprazole Floating Tablet:

Form the study of swelling index of batch F1-F8 are studied. All of the formulation tablet swelling index were determined 85.20%, which is within a good range are shown in table IX.

Table VII: Pre-compression evaluation parameters

Formulation code	Bulk density (gm/ml)	Tapped density (gm/ml)	Hausner’s ratio	Carr’s Index (%)	Angle of repose (θ)
F1	0.42 ±0.02	0.49 ±0.02	1.16	14.28 ±4.17	23.46 ±3.70
F2	0.39 ±0.04	0.45 ±0.12	1.15	13.33 ±5.56	24.41 ±3.62
F3	0.38 ±0.06	0.46 ±0.9	1.21	17.39 ±5.30	23.31 ±4.96
F4	0.34 ±0.02	0.41 ±0.16	1.20	17.07 ±4.78	27.11 ±3.76
F5	0.33 ±0.03	0.40 ±0.02	1.21	17.5 ±4.17	26.79 ±3.48
F6	0.38 ±0.03	0.44 ±0.02	1.15	13.63 ±4.17	22.29 ±3.48
F7	0.37 ±0.03	0.42 ±0.02	1.13	11.90 ±4.17	26.56 ±3.48
F8	0.38 ±0.08	0.46 ±0.08	1.13	11.62 ±3.98	21.65 ±4.82

Table 8: Post compression evaluation for Pantoprazole floating tablet

Formulation code	Weight Variation (mg)	Thickness (mm)	Hardness (kg/cm2)	Friability (%)	% Assay	Floating Lag Time (Sec)	Floating Time (Hrs.)
F1	245 ±1.38	4.1 ±0.19	4.7 ±0.25	0.81 ±0.02	96.4	31	12
F2	246 ±0.98	4.2 ±0.26	4.9 ±1.12	0.41 ±0.04	92.3	36	14
F3	248 ±1.12	5.0 ±0.84	5.0 ±0.96	0.28 ±0.06	91.5	41	16
F4	245 ±1.44	4.2 ±0.92	4.8 ±0.88	0.85 ±0.04	97.8	46	12
F5	247 ±1.48	4.3 ±0.78	4.9 ±0.74	0.41 ±0.08	95.1	44	14
F6	246 ±1.48	4.4 ±0.78	5.2 ±0.74	0.36 ±0.08	92.2	43	15
F7	244 ±1.48	4.5 ±0.78	5.1 ±0.74	0.35 ±0.08	98.05	36	17
F8	248 ±1.16	4.7 ±0.62	5.4 ±0.28	0.21 ±0.02	98.6	34	16

Fig 8: Images of Pantoprazole floating tablet in 0.1 N HCL

Table IX: Characterization of swelling index

Time (Hrs)	F1	F2	F3	F4	F5	F6	F7	F8
0	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00
0.5	12.10	17.20	16.80	13.17	13.20	14.34	14.34	16.10
1	27.52	29.40	28.10	24.0	24.30	26.92	26.80	25.63
1.5	32.33	40.30	38.88	33.20	33.33	36.20	36.20	35.21
2	49.55	54.63	47.63	37.41	45.55	53.63	42.63	40.38
3	52.33	62.15	58.60	45.20	57.33	58.21	56.60	44.20
4	55.63	68.63	62.33	64.66	59.63	65.56	64.33	58.20
5	68.60	71.54	75.45	68.23	67.60	68.12	78.45	67.25
6	76.00	77.20	85.20	72.10	75.40	74.20	82.20	79.20

Table X: In-Vitro % Drug Release of Pantoprazole floating tablet in 0.1 N HCL

Time (Hrs.)	F1	F2	F3	F4	F5	F6	F7	F8
0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
0.5	9.49±0.11	9.49±0.14	9.49±0.20	9.49±0.12	9.49±0.15	9.49±0.18	9.49±0.16	9.49±0.17
1	11.52±0.48	11.21±0.40	12.16±0.42	12.79±0.44	14.38±0.47	11.84±0.41	12.32±0.43	12.63±0.45
1.5	13.60±0.69	13.99±0.65	14.95±0.62	14.79±0.67	16.23±0.61	14.55±0.63	14.15±0.66	14.00±0.68
2	15.19±0.67	15.75±0.65	17.10±0.62	17.81±0.69	17.58±0.71	16.54±0.66	16.78±0.75	16.62±0.72
3	18.45±0.68	18.93±0.72	20.60±0.71	20.76±0.68	20.92±0.65	19.17±0.70	19.57±0.67	19.09±0.64
4	23.14±0.35	27.03±0.38	24.98±0.33	25.77±0.31	25.53±0.29	25.44±0.36	25.29±0.31	24.33±0.32
5	29.51±0.41	32.70±0.43	34.27±0.46	34.99±0.44	35.46±0.47	34.83±0.51	34.98±0.49	33.00±0.48
6	39.21±0.63	43.42±0.67	46.20±0.60	44.70±0.58	47.16±0.61	45.49±0.65	44.70±0.66	42.79±0.69
7	50.19±0.21	51.88±0.25	54.27±0.24	51.97±0.22	53.64±0.25	55.22±0.27	54.82±0.29	52.59±0.31
8	62.14±0.42	64.60±0.47	66.60±0.41	56.05±0.44	61.92±0.48	67.55±0.45	58.20±0.47	59.54±0.48
9	74.88±0.64	72.75±0.61	79.10±0.59	67.72±0.63	67.51±0.62	75.31±0.65	66.22±0.67	65.91±0.69
10	79.47±0.35	78.58±0.37	86.46±0.41	73.80±0.36	74.91±0.33	78.91±0.35	74.35±0.40	77.12±0.42
11	87.65±0.30	84.08±0.28	90.31±0.24	81.68±0.23	83.27±0.21	85.67±0.26	81.13±0.36	85.82±0.38
12	92.06±0.41	91.48±0.44	95.87±0.46	92.18±0.48	93.62±0.45	94.90±0.43	93.05±0.41	97.19±0.47

The results of the kinetic study's correlation coefficient assessment showed that the drug release corresponded to first order release kinetics. It was determined that the value of r for zero order ranged from 0.9737-0.9878, which is close to 1, in comparison to the Higuchi square root, which ranged from 0.7811-0.8382, and the first order, which ranged from 0.8782-0.9212. Thus, it was thought that all formulas maintained a zero-order release pattern. To gain additional insight into the drug release procedure, the data were further fitted into Korsmeyer Peppas' exponential framework, Mt / Ma = Ktn. where "t" is the fraction of medication released after time "t," "k" is the kinetic constant, and "n" is the release exponent. This is a schematic of the drug transport system. The release exponent's (n) range is 0.977–1.141. All eight formulations (F1 through F8) conformed to the super case-II transport release mechanism, as shown by "n" values ranging over 0.89. Because of the relative complexity of the generated formulations, it could occur that a combination of erosion and diffusion dictated the drug release mechanism.

Fig 12: Comparative Zero Order release profile of formulations F1 to F8

Fig 13: Comparative First Order release profile of formulations F1 to F8

Fig 14: Comparative Higuchi release profile of formulations F1 to F8

Comparative Study with Marketed Preparation:

A comparison study will be conducted by using dissolution analysis between optimize formulation and marketed formulation. Form the study of % CDR of batch F8 and marketed preparation are studied and shows the result in table XIII.

Table XIII: Results of in vitro dissolution study of optimized Batch (F8) and marketed preparation

Sr. No.	Time (Hrs.)	% CDR of Optimized batch F8	% CDR of Marketed preparation
1	0.5	9.49±0.17	10.66±0.20
2	1	12.63±0.45	13.01±0.49
3	1.5	14.00±0.68	14.41±0.65
4	2	16.62±0.72	17.12±0.71
5	3	19.09±0.64	19.67±0.62
6	4	24.33±0.32	25.08±0.30
7	5	33.00±0.48	34.03±0.49
8	6	42.79±0.69	44.14±0.71
9	7	52.59±0.31	54.26±0.33
10	8	59.54±0.48	61.44±0.47
11	9	65.91±0.69	66.39±0.70
12	10	77.12±0.42	79.59±0.40
13	11	85.82±0.38	86.94±0.42
14	12	97.19±0.47	99.50±0.50

Fig 15: % CDR of optimized batch F8 and marketed preparation

Optimization of formulation using 2³ factorial design:

2³ factorial design was applied to the development and the formulation of Pantoprazole floating tablet by considering 3 factors and 2 levels (high, low) HPMC K4M, MCC and Beta cyclodextrin considered as independent factors and Drug Release and % assay was dependent variables. Because to found best optimization batch in research. The independent factors are shown in table XIV and dependent variables are shown in table XV.

Table XIV: Independent factors and levels for 2³ factorial design

Sr. No.	Independent Factor	Unit	Low (-1)	High (+1)
1	HPMC K4M	mg	40	120
2	Beta cyclodextrin	mg	40	120
3	MCC	mg	20	80

Table XV: Dependent factors and levels for 2³ factorial design

Sr. No.	Dependent Factor	Unit	Low (-1)	High (+1)
1	R1 % Drug Release	%	91.48	97.19
2	R2 % Assay	%	91.5	98.6

Full model for R1 (% drug release):

Final equation in terms of coded factors:

Drug Release= +101.19+3.63*A+4.24*B+0.84*C+0.37*A*B-0.59*A*C

It was found that the independent variables, viz. A (HPMC K4M) B (Beta Cyclodextrin) and C (MCC) had a Positive effect on Drug release as shown in fig.16.

Fig.16 Contour plot for R1 (% Drug release)

Full model for R2 (% Assay):

% Assay = +103.97+04.35*A+5.55*B+0.28*C+3.24*A*B-0.82*A*C

It was found that the independent variables, viz. A (HPMV K4M) B (Beta Cyclodextrin) and C (MCC) has Positive effect as shown in fig.18.

3D Response Surface Plot:

Impacts of beta-cyclodextrin, HPMC K4M, and MCC on drug release and percentage of Pantoprazole assay can be seen in fig. 3D response surface plot approved. From the above figure of the response curve of R1 (Drug release), it is observed as the concentration of HPMC K 4M increases from -1 (40) to +1 (120) and Beta Cyclodextrin increases from -1 (40) to +1 (120) and MCC increases from -1(20) to + 1(80) drug release increases significantly, as shown in fig.17. Response curve of R2 (% Assay), it is observed as the concentration of HPMC K4M increases from -1 (40) to +1 (120) and Beta Cyclodextrin increases from -1 (40) to +1 (120) and MCC increases from -1 (20) to +1 (80) % assay increases significantly, as shown in fig.19. Statistical model predicted run number 8 as an optimized formulation. Three experimental trials of run 8 were performed to validate the predicted batch. The study exhibited the results of responses i.e., drug release 97.19 % and % assay 98.60% of optimized batch.

Fig. 17 Effect of independent variables on drug release 3D surface plot.

Fig.18 Contour plot for R2 (% Assay)

Fig. 19: Effect of independent variables on % Assay 3D surface plot.

CONCLUSION:

Pantoprazole, a protein pump inhibitor (PPI), has been suggested to treat acute benign gastric ulcers, acute duodenal ulcers, GERD, and as a preventative measure against duodenal ulcers. It works by selectively inhibiting the H+/K+ ATP enzyme in the gastric parietal cells, which affects locally on the stomach. For acute benign gastric ulcers, acute duodenal ulcers, and gastro-oesophageal reflux disease (GERD), the standard oral dosage recommendation is 40 mg provided for 8–12 weeks.

The result that yielded leads to the following adjustments. The functional group identified by the structure is evident in the infrared spectra of pure pantoprazole. Pantoprazole and all of the excipients are compatible, based on FTIR. Description of the Composition: Pre-compression aspects such as bulk density, tapped density, compressibility index, and Hausner's ratio are examined for the resultant formulation, as well as post-compression parameters like as thickness, hardness, weight variation, and friability. The USP-II paddle-type dissolving devices was used for assessing all eight formulations in vitro for a duration of 12 hours. Following this, the drug release profiles of each formulation were compared to those of the pure drug. The findings showed that all generated formulations exhibited a greater proportion of medication release in contrast to preparations that had been distributed commercially.

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Received on 01.01.2025 Revised on 21.01.2025

Accepted on 05.02.2025 Published on 03.03.2025

Available online from March 10, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(1):7-18.

DOI: 10.52711/0975-4377.2025.00002

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License. Creative Commons License.

Sr. No	Batch code	Zero Order Kinetics (R2)	First Order Kinetics (R2)	Higuchi Kinetics (R2)	Peppas (n)
1	F1	0.9737	0.8782	0.7811	1.141
2	F2	0.9867	0.9105	0.8166	1.042
3	F3	0.9812	0.8870	0.8046	1.066
4	F4	0.9872	0.9212	0.8337	0.996
5	F5	0.9853	0.9204	0.8382	0.977
6	F6	0.9854	0.9056	0.8172	1.034
7	F7	0.9878	0.9203	0.8290	1.009
8	F8	0.9825	0.8915	0.8007	1.099

Mathematical Modeling of Drug Release Profile:

Release Kinetic Studies:

Comparative Study with Marketed Preparation:

A comparison study will be conducted by using dissolution analysis between optimize formulation and marketed formulation. Form the study of % CDR of batch F8 and marketed preparation are studied and shows the result in table XIII.

Fig 15: % CDR of optimized batch F8 and marketed preparation

Sr. No.	Parameter	Result
1	Weight Variation (mg)	248 ±1.16
2	Diameter (mm)	10.00
3	Thickness (mm)	4.7 ±0.62
4	Hardness (kg/cm²)	5.4 ±0.28
5	Friability (%)	0.21 ±0.02
6	Drug Release (%)	97.19 ±0.47 (In 12Hrs)