Centre for Pharmaceutical Sciences, Jntuh University college of Engineering, Science and Technology, Hyderabad, Kukatpally, Telangana - 500085.
The present study focused on the design, formulation, and evaluation of gastroretentive floating microspheres of famotidine aimed at improving gastric residence time and providing sustained drug release. Famotidine, a histamine H?-receptor antagonist, is conventionally used for the management of peptic ulcers, Zollinger–Ellison syndrome, and gastroesophageal reflux disease, but its short half-life (2.5–3.5 h) and narrow absorption window restrict its clinical efficacy. To overcome these limitations, floating microspheres of famotidine were prepared using sodium alginate and gelatin as polymers, sodium bicarbonate as a gas-generating agent, and calcium chloride as a cross-linker by ionotropic gelation method. A total of twelve formulations (F1–F12) were developed and evaluated for percentage yield, drug content, entrapment efficiency (EE%), floating behavior, buoyancy, swelling index, bulk density, particle size, in-vitro drug release, and drug release kinetics. Among the formulations, F10 was identified as the optimized batch, showing high yield (90.1%), drug content (98.3%), and entrapment efficiency (90.8%). Floating lag time was minimal (58 s), with buoyancy of 95.6% at 2 h and total floating time exceeding 12 h. The in-vitro dissolution profile demonstrated sustained release up to 12 h (97.8%), compared to a marketed tablet which released >90% drug within 1 h. Release kinetics indicated Higuchi and Korsmeyer–Peppas models best described the mechanism, with anomalous transport involving diffusion and polymer relaxation. Accelerated stability studies (ICH guidelines) confirmed F10 retained stability for 3 months under 40 °C/75% RH with no significant variation in physicochemical or functional parameters. These findings demonstrate that famotidine-loaded floating microspheres represent a promising gastroretentive controlled-release system, with potential clinical advantages such as reduced dosing frequency, enhanced patient compliance, and sustained therapeutic efficacy in peptic ulcer management.
Peptic ulcer disease (PUD) continues to be a significant health concern worldwide, affecting nearly 10% of the global population. Despite advances in treatment such as proton pump inhibitors (PPIs) and H? receptor antagonists (H?RAs), recurrence and complications remain common due to factors such as Helicobacter pylori infection, NSAID use, smoking, and genetic predisposition. Famotidine, a potent H?RA, effectively reduces gastric acid secretion but suffers from short plasma half-life, variable bioavailability, and the need for frequent administration.
Gastroretentive drug delivery systems (GRDDS) have emerged as a promising approach for drugs with a narrow absorption window in the stomach or proximal small intestine. Floating drug delivery systems (FDDS), in particular, prolong gastric residence time by remaining buoyant in gastric fluid, ensuring controlled and site-specific drug release. Microspheres, or microballoons, offer additional advantages of high surface area, uniform distribution in the stomach, and controlled release properties.
The present research was undertaken to formulate and evaluate famotidine floating microspheres using ionotropic gelation, with the objective of improving gastric residence, sustaining drug release, and enhancing therapeutic efficacy compared to conventional dosage forms.
2. MATERIALS AND METHODS
2.1 MATERIALS
Famotidine was obtained as gift sample. Sodium alginate, gelatin, sodium bicarbonate, and calcium chloride were used as polymeric and crosslinking agents. Other excipients included hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), Tween 80, ethanol, acetone, and distilled water. All chemicals used were of analytical grade.
2.2 Preparation of Microspheres
Microspheres were prepared by ionotropic gelation technique. Aqueous solutions of sodium alginate (1.5–3.0% w/v) and gelatin (0.25–0.75% w/v) were used to disperse famotidine uniformly. Sodium bicarbonate (8–12% w/w of polymer) was added as a gas-generating agent. The dispersion was dropped into calcium chloride solution (2.5–5.0% w/v) under continuous stirring at 300–600 rpm using a syringe. Spherical microspheres formed instantaneously due to ionic crosslinking. The beads were allowed to cure for 20–30 min, collected, washed with water, and dried at 40 °C. Twelve formulations (F1–F12) were developed by varying polymer and effervescent concentrations.
Table-5.2: Formulation table of Famotidine Floating Microspheres
|
Code |
Famotidine (mg/100 mL) |
Sodium alginate (% w/v) |
Gelatin (% w/v) |
NaHCO? (% w/w of polymer) |
CaCl? bath (% w/v) |
Curing time (min) |
|
F1 |
1000 |
1.5 |
0.25 |
8 |
2.5 |
20 |
|
F2 |
1000 |
1.5 |
0.50 |
10 |
2.5 |
20 |
|
F3 |
1000 |
1.5 |
0.75 |
12 |
3.0 |
20 |
|
F4 |
1000 |
2.0 |
0.25 |
8 |
3.0 |
20 |
|
F5 |
1000 |
2.0 |
0.50 |
10 |
3.0 |
20 |
|
F6 |
1000 |
2.0 |
0.75 |
12 |
3.5 |
20 |
|
F7 |
1000 |
2.5 |
0.25 |
8 |
3.5 |
25 |
|
F8 |
1000 |
2.5 |
0.50 |
10 |
3.5 |
25 |
|
F9 |
1000 |
2.5 |
0.75 |
12 |
4.0 |
25 |
|
F10 |
1000 |
3.0 |
0.25 |
8 |
4.0 |
25 |
|
F11 |
1000 |
3.0 |
0.50 |
10 |
4.5 |
25 |
|
F12 |
1000 |
3.0 |
0.75 |
12 |
5.0 |
25 |
2.3 Evaluation Parameters
Percentage yield: Ratio of actual dried microsphere weight to total polymer + drug weight.
Drug content (DC): Measured spectrophotometrically (λmax 264 nm) after dissolving microspheres in 0.1 N HCl.
Entrapment efficiency (EE%): Practical drug content vs. theoretical drug content.
Floating properties: Floating lag time (FLT) and total floating time (TFT) evaluated in 0.1 N HCl (37 °C, USP paddle apparatus).
In-vitro buoyancy (%): Ratio of floating beads to total beads at 2 h.
Swelling index: Change in bead weight after immersion in 0.1 N HCl.
Bulk density: Weight/volume ratio of beads in a measuring cylinder.
Particle size: Measured by optical microscopy with image analysis software.
In-vitro dissolution: USP type II apparatus, 900 mL 0.1 N HCl, 50 rpm, 37 °C, samples withdrawn at intervals up to 12 h.
Drug release kinetics: Data fitted to Zero order, First order, Higuchi, and Korsmeyer–Peppas models.
Stability studies: ICH guidelines (40 °C/75% RH, 3 months) in sealed HDPE containers.
3. RESULTS AND DISCUSSION
3.1 Analytical method by UV-Visible spectrophotometry
Fig-6.1: Lambda max of Famotidine
Famotidine displays characteristic absorption peaks due to its chromophoric groups, with the most prominent and sharp absorption observed around 264 nm, which corresponds to its λmax.
Fig-2: Calibration curve of Famotidine in 0.1N HCl
The calibration curve shows a linear relationship between concentration and absorbance in the range of 2–10 ppm. The regression equation was found to be y = 0.0381x + 0.0016 with a correlation coefficient R² = 0.9941, indicating good linearity.
3.2 Percentage Yield, Drug Content and Entrapment Efficiency
The yield of microspheres increased with higher polymer concentration, ranging from 72.4% (F1) to 90.1% (F10). Drug content improved steadily, with maximum in F10 (98.3%). Entrapment efficiency also increased, reaching 92.7% in F12, attributed to dense polymeric matrices reducing drug leaching.
3.2 Floating Properties
FLT decreased from 118 s in F1 to 49 s in F12, while TFT extended beyond 12 h in higher formulations. F10 showed optimal performance with minimal lag time (58 s) and prolonged buoyancy (15 h), demonstrating effective incorporation of effervescent agents.
3.3 Physicochemical Characteristics
Bulk density decreased from 0.61 g/cm³ (F1) to 0.46 g/cm³ (F12), supporting buoyancy. Swelling index increased from 118% to 171%, indicating enhanced hydration and controlled release. Particle size increased from 512 µm (F1) to 681 µm (F12).
3.4 In-vitro Drug Release
The marketed tablet exhibited rapid release (>90% within 1 h). In contrast, F10 microspheres showed controlled release with only 15% release at 15 min, 50% at 2 h, and 97.8% at 12 h, demonstrating sustained release characteristics.
Table-6.3: In-Vitro Dissolution Profile of Famotidine (F10 vs Marketed Tablet) in 0.1 N HCl (n = 3, Mean ± SD)
|
Time (h) |
F10 Optimized Microspheres (% Release ± SD) |
Marketed Tablet (% Release ± SD) |
|
0.08 (5 min) |
6.2 ± 1.1 |
35.5 ± 2.0 |
|
0.17(10 min) |
10.8 ± 1.5 |
58.2 ± 2.5 |
|
0.2(15 min) |
15.4 ± 1.7 |
72.6 ± 3.1 |
|
0.5 (30 min) |
21.6 ± 2.1 |
89.8 ± 2.8 |
|
0.75(45 min) |
28.2 ± 2.4 |
95.6 ± 2.4 |
|
1.0 |
35.7 ± 2.2 |
98.1 ± 2.0 |
|
2.0 |
48.9 ± 2.6 |
99.3 ± 1.8 |
|
4.0 |
63.5 ± 3.0 |
– |
|
6.0 |
76.8 ± 3.4 |
– |
|
8.0 |
85.2 ± 3.1 |
– |
|
10.0 |
92.4 ± 3.2 |
– |
|
12.0 |
97.8 ± 2.8 |
– |
Fig-6.5: In-Vitro Dissolution Profile of Famotidine (F10 vs Marketed Tablet) in 0.1 N HCl (n = 3, Mean ± SD)
3.5 Release Kinetics
Kinetic modeling revealed that drug release followed Higuchi diffusion model (R² ≈ 0.98) and Korsmeyer–Peppas model (n ≈ 0.60), confirming anomalous non-Fickian transport involving diffusion and polymer swelling. Hixson–Crowell model further indicated contribution of surface erosion.
3.6 Stability Studies
Stability evaluation of F10 for 3 months revealed no significant changes in DC, EE%, FLT, TFT, or Q12h release profile (<5% variation). Microspheres retained discrete spherical morphology, confirming stability under ICH accelerated conditions.
4. CONCLUSION
The study successfully formulated famotidine floating microspheres using ionotropic gelation. Optimized batch (F10) exhibited high entrapment efficiency, excellent buoyancy, and sustained drug release over 12 h compared to the marketed conventional dosage form. The formulation followed Higuchi and Korsmeyer–Peppas release kinetics, indicating diffusion- and swelling-controlled drug release. Accelerated stability studies confirmed robustness of the formulation.
Famotidine floating microspheres thus represent a promising gastroretentive system for enhancing gastric residence, sustaining drug delivery, reducing dosing frequency, and improving patient compliance in the treatment of peptic ulcer disease.
REFERENCE
Anjitha C. J., Preethi Sudheer, Nimisha Jain*, Sindhu Subramanya Bhat, Akash Nayaka M., Jyothi S., Development and Evaluation of Meloxicam Nanostructured Lipid Carriers for Transdermal Delivery, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 9, 3428-3435 https://doi.org/10.5281/zenodo.17226717
10.5281/zenodo.17226717
