1. INTRODUCTION:

Oral route remains the preferred route for the administration of therapeutic agents owing to ease of administration, low cost of therapy and easy fabrication at industrial scale along with better patient compliance an effective oral drug delivery may depend upon many factors such as gastric emptying process, drug release from the dosage form decide pKa, gastrointestinal transit time of the dosage form and site of absorption of drug^1,2. The diversity in these systems is owed to the numerous benefits obtained from designing them. These benefits include increased drug bioavailability, decreased side effects and dosing frequency, in addition to increased patient compliance. gastro retentive delivery system are mainly intended for drugs having a narrow absorption window, a biological half-life ranging from 2-8hr and drugs taken in multiple daily doses³. The GRDDS greatly improves the pharmacotherapy of the stomach through local drug release, leading to high drug concentration at the gastric mucosa^4,5. Microcapsules are tiny spheres with a core material surrounded by a protective wall. They have a wide range of applications, from controlled drug delivery to food preservation⁶. A spherical particle with the size varying between 50nm to 2nm containing a core substance. Lafutidine is an anti-ulcer medication widely used in the treatment of GERD reflux disease and peptic ulcer disease⁷. It belongs to a class of drugs known as histamine H2 receptor antagonists (H2RAs), which function by reducing the amount of stomach acid produced. One notable characteristic of Lafutidine is its quick onset of action⁸. When taken by mouth, it is rapidly absorbed into the bloodstream and reaches its highest concentration within one to three hours. This rapid absorption is due to its high lipophilicity, which allows it to pass through cell membranes easily. Once in the bloodstream, Lafutidine is distributed to the stomach. In order to prolong the effect microencapsulation was done of this drug^9,10.

2 MATERIALS AND METHODS:

The chemicals and polymer materials used included, the drug Lafutidine, wall polymer materials like synthetic polyelectrolyte, often a biopolymer like sodium alginate, ethyl cellulose and HPMC. A solution containing multivalent cation like calcium chloride (Cacl2), commonly used to gel anionic polymers like ethyl cellulose. Triphosphate often used as an anionic cross- linker for cationic polymer like HPMC. Other than these, the solvent used included one listed in table 1 under.

Table 1: List of solvents used

Solvent / medium	pH level
0.1N HCL	1.2
Distilled water	7.0
Phosphate buffer	7.4
Methanol	-
Ethanol	-

2.1 Pre-Formulation Study:

2.1.1 Organoleptic Evaluation:

The drug substance was visually inspected for color and physically examined for order and taste.

2.1.2 Solubility Analysis:

The ‘shake – flask’ or phase equilibrium method is used. An excess amount of Lafutidine is added to various solvents (water, 0.1N HCL, phosphate buffers of PH 4.5, 6.8, and 7.4). The mixtures are agitated for 24-48hours at room temperature, filtered, and analyzed via UV - Spectrophotometry.

2.1.3 Melting Point Determination:

Small amount of drug is placed in a capillary tube and heated in a digital melting point apparatus.

2.1.4 Identification & Purity (FTIR):

By FTIR (Fourier Transform Infrared Spectroscopy), the purity of the sample was accessed. The drug is mixed with potassium Bromide (KBr) were mixed at a ratio of 1:100. This mixture was compressed into a pellet by applying 10 tons of pressure with a hydraulic press. A wave number range of 4000 cm-1 to 400 cm-1 was used to scan the pellets. An FTIR instrument was used to conduct the spectral study.

2.1.5 Differential Scanning Calorimetry Studies:

The thermal examination was carried out using the mettle Toledo DSC-8233 system, which includes a differential scanning calorimeter and a computerized data station. A nitrogen flow was applied while weighed samples of pure medicine, physical mixes of drugs and polymers, and mixtures of polymers were heated at a rate of 10 c /min between 40 and 200^oC. DSC research sheds light on how various materials interact with one another at various temperatures.

2.2 Determination of λMax and Calibration Curve of Lafutidine in 0.1N HCL:

Take the 10μg/ml of above solution was taken and scanned it in the UV range of 200nm to 400nm against a blank. identify the peak. For Lafutidine, the lambda max is typically found at 279nm, 286nm, or 290nm, depending on the solvent/pH. Following careful weighing Lafutidine (10mg) was added to a volumetric flask. With a 100ml capacity. It was next dissolved in 25ml of 0.1N HCL and then diluted with the same solution to a final volume of 100ml. To attain a concentration of between 5 and 30μg/ml, afore mentioned solution was further diluted. The absorbance of the resulting solution was measured at 290nm using a UV Visible spectrophotometer. HCL (0.1N) was used as the standard for the blank. After creating calibration plot, the linearity was determined. Three runs of the calibration curve were made.

2.3 Formulation of Microcapsule of Lafutidine:

Lafutidine microcapsule were prepared by ionic gelation technique using polymers sodium alginate/ethyl cellulose and HPMC K4M. Sodium bicarbonate was used as a floating agent and calcium chloride was used as crosslinking agent. The composition of different Microcapsule formulation of Lafutidine are listed in table 2 under.

Based on pharmaceutical research protocols, the preparation generally follows these steps:

2.3.1 Preparation of The Polymer – Drug Mixture:

Polymer dissolution: sodium alginate/ethyl cellulose (100g, as gelling agent) is dissolved in distilled water (100ml) to create a 2-3% w/v solution. Other polymer like HPMC (25mg) may be added to control the drug release rate.

Drug Addition: an accurately weighed amount of Lafutidine (50mg) is added to the ethyl cellulose solution.

Floating agent: Lafutidine need a to stay in the stomach, a gas–generating agent like sodium bicarbonate (NaHCO3) 15mg of calcium carbonate.

Homogenization: The mixture is stirred or sonicated to ensure the drug is uniformly dispersed and air bubbles are removed.

2.3.2 Gelation and Cross-Linking:

Dropping: The mixture is loaded into a syringe and extruded drop-wise through a fine gauge needle (e.g 23G or 26G) into a 1-5% Calcium Chloride (CaCl2) solution. The droplets instantly form spherical beads. These are left in the 100ml of CaCl2 solution and stirred at 100rpm. After stirring for 10minutes the obtained microcapsules were washed with water and dried for 30-60minutes to ensure complete cross-linking and mechanical strength.

2.3.3 Collection and Drying:

Separation: the microcapsules are collected by filtration

Washing: they are washed with distilled water to remove excess calcium ions from the surface.

Drying: the beads are dried at room temperature or in hot oven (approx. 40-50^oC) until a constant weight is achieved.

2.4 In Vitro Release Study:

The release study (in vitro study) was made on lafutidine microcapsule formulations and pure lafutidine powder which involved the dissolution apparatus USP-II and dialysis bag method. The same amount of Lafutidine as the pure drug powder, as well as in the microcapsule form of the drug (10mg) was made. This amount was put in the dialysis bag, and then engaged in dissolution medium. The initial two hours were spent in the dissolution medium with the 900 ml of HCl buffer pH (1.2) +0.5% tween 20. Following this 1.5ml of phosphate buffer pH (6.8) +0.5% tween 20 replaced afterwards and proceeded only 1hour. The dissolution apparatus was unsettled at 37+0.5C and revolutions rate of 50rpm throughout the total time of 3hours. Frequent sampling of dissolution mediums was persisted during the span of study that incorporate a 5ml samples will be taken out at regular action of time intervals of 15 minutes and each taken out samples will be replaced by 5ml of fresh corresponding medium so as to keep off the sink condition state. The filter membrane of 0.45µm should be used to filter all the withdrawn samples. The sample analysis, then, in UV-visible spectrophotometer of the content of Lafutidine was at 290nm.

2.5 Scanning Electron Microscopy (SEM) study:

The SDM study was conducted to reveal the morphology and distribution of the droplets in the prepared system of the microcapsules. One drop of microcapsule of Lafutidine (of optimized formulation F4) was put on a glass slide and then detected.

3 RESULT AND DISCUSSION:

3.1 Preformulation Studies:

3.1.1 Melting Point & Organoleptic Properties of Lafutidine:

These are listed in table 3 under. Study of these parameters helps confirm the purity and crystalline nature of the sample drug procured.

Table 3: Different studied properties of Lafutidine

Drug	Lafutidine
Melting Point Range	Literature	98-101^oC
Melting Point Range	Practical	98-100^oC
Organoleptic Properties	Colour	White to off-white
	State	Crystalline powder
	Odor	Odorless
	Taste	slightly bitter

3.1.2 Solubility Study:

The Solubility outcomes in different medias of Lafutidine is compiled in table 4 under. The solubility of Lafutidine as observed in 0.1N HCL (pH 1.2) and buffer of pH values 4.6 (acetate buffer) and 6.8 (phosphate buffer) are presented in table. Lafutidine exhibited a pH dependent solubility in these aqueous buffers. Higher solubility of Lafutidine was observed at acidic pH values, while the solubility dropped rapidly as the pH increased. and organic solvents like methanol slightly soluble (approx. 0.5 mg/ml) and ethanol sparingly soluble.

Table 4: Solubility profile of Lafutidine

Solvent / medium	pH level	Solubility result	Result
0.1N HCL	1.2	~3.5 – 5.0 mg/ml	Highly soluble
Distilled water	7.0	< 0.03mg/ml	Practically insoluble
Phosphate buffer	7.4	~0.09mg/ml	-
Methanol	-	> 10mg/ml	Soluble
Ethanol	-	>~5	Soluble

3.2 Calibration Curve for Lafutidine:

Determination of (λmax) Wavelength of maximum absorbance of Lafutidine was found to be 290nm in Methanol and 0.1N HCL (figure 1). The calibration curve for Lafutidine in 0.1N HCL is shown. The graph of absorbance or concentration for Lafutidine was found to be linear in the concentration range of 5-30μg/ml at 290nm (figure 2), in a graph with concentration on the X- axis and Absorbance on the Y- axis. The r2 of the calibration curve was found to be 0.9996. The standard calibration curve detail for Lafutidine is shown in table 5.

Fig. 1: UV- Visible (UV- VIS) Absorption Spectra of Lafutidine

In this electromagnetic spectrum in the ultraviolet (200 -400nm) region, three peaks are obtained. A primary peak at ~ 210nm, is highest point on the graph, with an absorbance value of approximately 0.80. Secondary peak (~250nm) appears immediately after the first with an absorbance of 0.70. Tertiary lower peak at ~290nm, is a broader peak occurs further into the UV range with an absorbance of approximately 0.15 value. Based on the literature study, we went for selecting this as the λmax peak for Lafutidine. After 300nm the absorbance drops to nearly zero and remains flat.

Table 5: Concentration and absorbance values for Lafutidine in 0.1N HCl

Concentration (μg/ml)	Absorbance
05	0.0124
10	0.024
15	0.0367
20	0.0485
25	0.062
30	0.0745

Fig. 2: Calibration Curve of Lafutidine

3.3 Differential Scanning Calorimetric (DSC) Studies:

DSC is a thermogram of Lafutidine sample. It displays the heat flow as a function of time and temperature during a controlled heating and cooling test. The DSC thermogram graph shown in figure 3, has X-axis (bottom) as time in 0 to 12min. and X- axis (top) as temperature in degrees Celsius (0^oC to ~150^oC) with a target segment from 25^oC to 150^oC. The heating rate was 10.0k/min or c/min. Y-axis (left) indicating heat flow in milliwatts per milligram (DSC/(mW/mg). The arrow pointing down with ‘exo’ indicates that exothermic events (heat releasing) appear as downward deflections (negative mW/mg), and endothermic events (heat- absorbing) would appear as upward deflections. Y- axis (Right) flow rate in milliliter per minute. Curves in solid blue line, are primary DSC heat flow signal for the Lafutidine. Red dotted line programmed temperature ramp over time.

Fig. 3: DSC thermogram of Lafutidine

This endothermic peak corresponds to the melting point or a phase transition temperature of the pure Lafutidine sample. Pure Lafutidine typically reports its melting point in the range of 99^oC to104^oC. The peak in this graph is consistent with those findings.

3.4 FTIR (Fourier transform infrared spectroscopic studies)

The FTIR spectrum of Lafutidine is shown in figure 4 below. FTIR spectrum of Lafutidine showed all the peaks corresponding to the functional groups present in the structure of Lafutidine.

Fig. 4: FTIR spectra of Lafutidine

The major peaks for pure Lafutidine were seen as below, 3323.78 cm-1 for – NH stretching, 2794.40 cm-1 for – CH (alkyl) stretching, 1635.86 cm-1 for –C=O stretching, and 985 cm-1 for SO stretching, which confirms the important functional group Lafutidine.

3.4.1 Physical Compatibility Test:

Physical compatibility test using infrared spectroscopy for physical compatibility test FTIR of drug and excipients were mixed and kept strictly for 30 days. The spectrum was scanned over a frequency range 4000-400 cm-1 (figure 5). FTIR spectra of drug excipient mixture retained the characteristic functional the polymer and the drug show no interaction. Peaks of the drug as shown in figures below.

Fig. 5: IR spectra of Lafutidine + HPMC + Chitosan + Ethyl cellulose

The major peaks for pure Lafutidine were seen as below, 2913.06 cm-1 for –CH (alkyl) stretching 1524.71 cm-1 for –C=O stretching, and 938.65 cm-1 for SO stretching which confirms the important functional group Lafutidine.

3.5 In-Vitro Drug Release Study:

In vitro release of lafutidine microcapsules (F1-F4) and pure drug was prepared and dialyzed using dialysis bag technique in the presence of HCl buffer (pH1.2)-0.05% tweens 20 in the two cases and phosphate buffer (pH6.8)-0.05% tweens 20 in a single case respectively through the dialysis bag technique in their respective dissolution mediums. The order was demonstrated by the outcome of the drug release of microcapsules (F1-F4) and a pure powder drug, F4>F1>F3>F2>pure drug. As shown in the figure 6. The analysis of variance shows that the significant difference (P<0.05) was observed between the release of drug and time.

Fig. 6: In vitro release of Microcapsules and pure drug (SD ±1–2%)

The rate of release of the drug in the dissolution medium represents the action of the concentration of surfactant which will cause a high rate of drug release of will up to some point depending on the concentration of tween 20. This was the reason why diffusion of drug within dialysis bag to dissolution medium will take place in high concentration of surfactant resulting in lower release of drug.

3.6 Scanning Electron Microscope (SEM):

Scanning electron microscope SEM micrograph showcases the surface morphology of a specimen at a high magnification. In present study, the SEM micrograph illustrated a highly porous and irregular surface topography (figure 7). The materials appeared as a collection of interconnected, nodular clusters with varying grain sizes. These clusters exhibit a spheroidal to sub –spherical habit, typical of synthesized powders or sintered metallic surfaces. Porosity is significant inter granular porosity visible throughout the matrix. The presence of deep voids and channels suggests a high surface area to- volume ratio, which is often a desirable trait in applications such as catalysis, (surface Roughness) specimen displays high micro- roughness with no evidence of long-range crystalline order or smooth facets at this scale. Indicating a potentially polycrystalline or amorphous nature.

Fig. 7: SEM Images of Microcapsule

4 CONCLUSION:

In the present study, formulation and evaluation of sustained release micro particle system for the treatment of peptic ulcer has been successfully achieved. An attempt was made to prepare different lafutidine microcapsules which were characterized for in-vitro release and scanning electron microscopy. FTIR and DSC study was done to check the purity of the procured sample. Among all the formulations F4 was selected as optimized formulation. In vitro release study of formulation F4 showed it gave the highest release in the given time frame. The FTIR and DSC analyses confirmed the absence of drug- polymer interaction. From the results it can be concluded that the drug release from the microcapsule was controlled by the polymer proportion. The optimized formulation can thus give prolonged local residence time may lead to effective management of H. Pylori Induced peptic ulcer.

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Received on 24.04.2026 Revised on 18.05.2026

Accepted on 06.06.2026 Published on 07.07.2026

Available online from July 10, 2026

Res. J. Pharma. Dosage Forms and Tech.2026; 18(3):203-208.

DOI: 10.52711/0975-4377.2026.00030

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

Formulation code	Lafutidine (mg)	Ethyl cellulose	HPMC K4M (mg)	Sodium bicarbonate (mg)	Calcium chloride
F1	50	1%	25	15	1%
F2	50	1.2%	75	50	1%
F3	50	1.4%	100	75	1%
F4	50	1.6%	150	100	1%