TMP Universal Journal of Medical Research and Surgical Techniques
VOLUME 1 │ISSUE 2│YEAR 2025│ APR–JUN 2025
RECEIVED DATE
24/04/2025
ACCEPTED DATE
20/05/2025
PUBLISHED DATE
08/06/2025

Article Type : Research Article

Available online : ujmrst.twistingmemoirs.com/

FORMULATION DEVELOPMENT AND EVALUATION OF GASTRO RETENTIVE MICROSPHERES FOR THE DELIVERY OF ANTI- ULCER DRUG

Author : Darshan Jain 1 , Shaivad Shabee Hulhasan Abadi 2 * , Vinod Parihar3, Dr. Rupesh Soni4

1 Scholar of M. Pharm, Department of Pharmaceutics, B. R. Nahata College of Pharmacy, Mandsaur University, Mandsaur (M. P.), 458001
2, 3 Assistant Professor, Department of Pharmaceutics, B. R. Nahata College of Pharmacy, Mandsaur University, Mandsaur (M. P.), 458001
4 Professor, Faculty of Pharmacy, B. R. Nahata College of Pharmacy, Mandsaur University, Mandsaur (M. P.), 458001.

CORRESPONDING AUTHOR

Darshan Jain

Email : darshanjaindld@gmail.com

ABSTRACT

Gastroretentive microspheres are an advanced drug delivery system designed to enhance the effectiveness of anti-ulcer drugs by prolonging their retention in the stomach. This study focuses on the formulation, development, and evaluation of gastroretentive microspheres to improve drug absorption and therapeutic efficacy. The microspheres were prepared using different polymers to achieve controlled drug release and buoyancy. Various formulation techniques, including solvent evaporation and emulsion methods, were employed to create microspheres with desirable characteristics such as high drug entrapment, good floating ability, and sustained drug release. The developed microspheres were evaluated for particle size, drug-loading efficiency, floating behavior, and in-vitro drug release. Particle size ranged from 214–254 µm, ideal for gastric retention. Entrapment efficiency was 83.2%–92.1%, and drug loading ranged from 16.6%–19.2%, both increasing with higher HPMC concentration. Batches F3 to F6 remained buoyant for over 12 hours, indicating excellent floating capacity. Famotidine release was sustained over 12 hours, with slower release at higher polymer concentrations. The release followed a diffusion-controlled mechanism and fit best with the Higuchi model. HPMC’s polymeric matrix significantly delayed drug diffusion, supporting its role in sustained delivery. These findings confirm the effectiveness of the formulation in enhancing gastric residence and controlled drug release for anti-ulcer therapy.

Keywords: Gastroretentive drug delivery, Famotidine, Microspheres, Solvent evaporation, HPMC, Ethyl cellulose.

INTRODUCTION

Oral drug delivery remains the most convenient and widely used method of drug administration. However, a significant limitation of conventional oral delivery systems is the inability to maintain an adequate drug concentration at the site of absorption for an extended period. This is especially problematic for drugs that are absorbed in a narrow region of the gastrointestinal tract or that degrade in the lower intestines. 01 Gastroretentive drug delivery systems (GRDDS) have been developed to address these issues by prolonging the gastric residence time of drugs, thereby improving their bioavailability and therapeutic efficacy. These systems are particularly beneficial for drugs that have a narrow absorption window in the upper gastrointestinal tract, are unstable in the intestinal or colonic environment, or act locally in the stomach.02

Famotidine is an H2-receptor antagonist used to reduce gastric acid secretion. It is effective in the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). Famotidine has a relatively short plasma half-life of 2.5–4 hours and an oral bioavailability of approximately 40–45%, primarily due to poor absorption in the lower gastrointestinal tract. As a result, multiple daily doses are often required, which can reduce patient compliance.03

Microspheres offer several advantages for drug delivery, including targeted delivery, controlled release, and enhanced stability. Floating microspheres are a type of GRDDS that remain buoyant in the stomach for an extended period, thereby increasing the residence time and allowing for a sustained release of the drug. The formulation of Famotidine as floating microspheres using polymers such as ethyl cellulose and HPMC may provide an effective solution for enhancing its bioavailability and reducing the frequency of administration. 04

This study aims to formulate, optimize, and evaluate floating microspheres of Famotidine using a solvent evaporation technique. Parameters such as polymer concentration, drug-to-polymer ratio, stirring speed, and solvent composition were investigated for their influence on the physicochemical properties of the microspheres. The developed microspheres underwent characterization for size distribution, drug loading efficiency, floating capability, and release behavior in vitro.05

MATERIALS AND METHODS

Materials

Preparation of Microspheres Preparation of Internal Phase:

A specific amount of famotidine was accurately weighed and either dissolved or uniformly dispersed in a solvent mixture containing DCM and ethanol. The selected polymers HPMC also dissolved in this organic phase to create a homogenous drug-polymer solution.

Emulsification: The drug-polymer solution was slowly added dropwise into an aqueous phase containing 1–2% PVA while stirring continuously using a magnetic or overhead stirrer. This process resulted in the formation of a stable oil-in-water (O/W) emulsion, with the organic droplets dispersed in the continuous aqueous phase. 07

Solvent Evaporation:

The emulsion was stirred at a consistent speed ranging from 500 to 1000 rpm for a period of 2–4 hours at room temperature. This allowed gradual evaporation of the volatile solvents (DCM and ethanol), leading to the solidification of the polymer matrix and entrapment of the drug within the formed microspheres.

Collection of Microspheres:

After solvent removal, the hardened microspheres were separated by filtration or centrifugation . They were washed multiple times with distilled water to remove residual surfactant and unencapsulated drug. The final microspheres were dried either under ambient conditions or using a vacuum desiccator to obtain free-flowing, dry particles. 08

Evaluation Parameters

The formulated gastroretentive floating microspheres of famotidine were subjected to comprehensive physicochemical, functional, and performance-based evaluations to ensure quality, efficacy, and suitability for sustained gastric retention. The evaluation parameters included:

Physical Mixture : All characteristic peaks of famotidine and HPMC with no major shifts. These peaks were retained in the physical mixture without significant shifts or disappearance, indicating no major between famotidine and HPMC.

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Figure 3.1: FTIR spectra of a) Famotidine, b) HPMC, c) Physical Mixture

DSC Analysis: DSC thermograms showed a sharp endothermic peak for famotidine at ~164°C, corresponding to its melting point. The physical mixture with HPMC also showed this peak with minimal shift, suggesting no thermal incompatibility. The polymer exhibited a broad peak characteristic of its amorphous nature.

Table 3.3: DSC Thermograms of Famotidine, HPMC, and Physical Mixture

Sample

Peak Temp (°C)

Type of Transition

Interpretation

Famotidine

~164

Sharp Endothermic (melting)

Indicates crystalline nature of

drug

HPMC

~75

Broad Endothermic (glass

transition)

Amorphous polymer response

Physical

Mixture

~75 & ~164

Combined peaks

No significant shift → No

interaction

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Figure 3.2: DSC Thermogram of (a) Famotidine, (b) HPMC, (c) Physical Mixture

Drug Entrapment and Loading Efficiency

The entrapment efficiency ranged from 83.2% to 92.1% , while drug loading ranged from 16.6% to across batches F1 to F6. A clear upward trend in both parameters was observed with an increase in HPMC concentration.

Floating Behavior and Buoyancy Time

Floating Lag Time is the time taken by the microspheres to emerge to the surface. Total Floating Duration is the total duration for which the microspheres remained buoyant.

Table 3.4: Floating Behaviour of Famotidine Microsphere

Batch

Floating Lag Time (sec)

Total Floating Duration (hrs)

Floating Behavior

F1

58 ± 4

>8

Moderate

F2

43 ± 3

>10

Good

F3

31 ± 2

>12

Excellent

F4

25 ± 2

>12

Excellent

F5

22 ± 2

>12

Excellent

F6

18 ± 1

>12

Excellent

In Vitro Drug Release Profile

The drug release profile of batches F1 to F6 was evaluated using a USP Type II (paddle) dissolution apparatus. The study was conducted in 900 mL of simulated gastric fluid (pH 1.2, without enzymes) maintained at a temperature of 37 ± 0.5°C and a paddle rotation speed of 100 rpm. Samples were collected at specific time intervals—0.5, 1, 2, 4, 6, 8, 10, and 12 hours. At each sampling point, 5 mL of the dissolution medium was withdrawn and replaced with an equal volume of fresh medium to maintain sink conditions. The collected samples were then filtered, appropriately diluted, and analyzed using a UV- Visible spectrophotometer at 265 nm to determine the amount of drug released.

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Figure 3.3: in Vitro Drug Release Profile (% Drug Released vs. Time)

Table 3.5: In Vitro Drug Release Profile of Microsphere

Time (hr)

F1 (%)

F2 (%)

F3 (%)

F4 (%)

F5 (%)

F6 (%)

0.5

18.4

16.2

14.5

12.7

11.5

10.2

1

28.9

26.4

23.5

20.1

18.3

16.5

2

46.7

42.1

37.8

32.5

29.6

27.1

4

65.2

59.3

52.6

45.8

41.2

38.5

6

82.5

75.6

68.3

60.4

55.3

51.8

8

91.1

86.5

78.4

70.9

65.3

60.4

10

95.3

91.2

84.5

76.8

70.2

64.3

12

98.6

94.7

89.3

81.4

74.6

69.2

Increasing HPMC concentration retards drug release by increasing matrix viscosity, slowing solvent penetration and drug diffusion and enhancing gel barrier strength. Ethanol, as a co-solvent, helped maintain uniform drug dispersion but did not interfere with the sustained release effect.

Kinetics and Mechanism of Drug Release

Table 3.6: Drug Release Kinetics and Model Fitting for Microsphere (R² Values)

Batch

Zero-Order

First-Order

Higuchi

Korsmeyer-Peppas (n value)

Best Fit Model

F1

0.943

0.977

0.987

0.65

Higuchi / Peppas

F2

0.938

0.972

0.984

0.62

Higuchi / Peppas

F3

0.927

0.965

0.981

0.60

Higuchi

F4

0.918

0.958

0.979

0.58

Higuchi

F5

0.902

0.944

0.974

0.55

Higuchi

F6

0.893

0.938

0.970

0.52

Higuchi

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Figure 3.4: (a) Graph of Higuchi Plot, (b) Graph of Korsmeyer–Peppas Plot

The drug release from Famotidine-loaded floating microspheres follows diffusion-controlled release , best described by the Higuchi model .

Optimization and Statistical Interpretation

The optimization of the Famotidine-loaded microspheres was carried out using a 3² full factorial design as part of the Design of Experiments (DoE) approach. Two independent formulation variables were studied at three levels each: polymer ratio (HPMC:Ethyl cellulose) (X₁) and stirring speed during emulsification (X₂). This design generated nine experimental runs to evaluate the influence of formulation variables on response parameters such as particle size, drug entrapment efficiency, and percentage drug release. The independent variables selected were:

3D surface and contour plots confirmed that increasing HPMC concentration while maintaining moderate ethanol levels enhanced overall formulation performance.

UV Spectroscopy Analysis

Standard solutions of famotidine were prepared in concentrations ranging from 2 to 20 µg/mL in 0.1N HCl. The absorbance of each solution was measured at 265 nm using a UV spectrophotometer.

Table 3.8: Calibration Data of Famotidine in 0.1N HCl

Concentration (µg/mL)

Absorbance (265 nm)

2

0.123

4

0.245

6

0.368

8

0.492

10

0.615

12

0.741

16

0.985

20

1.234

The resulting standard curve showed excellent linearity, with a correlation coefficient ( R² ) of 0.998 , confirming that Beer–Lambert's law was obeyed over this concentration range.

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Figure 4: UV calibration curve of Famotidine in 0.1N HCl

CONCLUSION

This study successfully formulated and evaluated gastroretentive floating microspheres of Famotidine using HPMC and ethyl cellulose. Among various formulations, ethyl cellulose-based microspheres

demonstrated optimal particle size, high entrapment efficiency, excellent buoyancy, and sustained drug release over 12 hours. The use of hydrophobic polymer helped prolong the gastric residence time and improve the drug release profile.

In vitro drug release studies showed a sustained release pattern, with the optimized formulation releasing about 92% of the drug over 12 hours. This prolonged release profile is suitable for maintaining therapeutic levels of Famotidine over an extended period. Drug release kinetics were analyzed using mathematical models, and the release profile best fitted the Higuchi model, indicating a diffusion-controlled drug release mechanism from the polymeric matrix.

Fourier Transform Infrared Spectroscopy (FTIR) studies confirmed the chemical stability of Famotidine within the formulation, showing no significant interactions between the drug and polymers. Differential Scanning Calorimetry (DSC) analysis revealed a reduction in the crystallinity of the drug, indicating partial amorphization and better molecular dispersion in the polymer matrix, which likely contributed to the sustained release behavior. Moreover, statistical optimization using a factorial design showed that the experimental results closely aligned with predicted values, affirming the reliability and precision of the optimization process.

Gastroretentive microspheres provide a promising approach for improving the therapeutic efficacy of drugs like Famotidine that have narrow absorption windows and require prolonged presence in the stomach.

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