Formulation and Evaluation of Metformin Gastroretentive Drug Delivery System

Yash S. Bachhav, Pallavi S. Bachhav, Ritesh R. Karmarkar, Dipika H. Gosavi, Pratiksha S. Shewale, Nikhil M. Kadam, Radhika V. Kharote, Bhagyashri S. Suryawanshi,

doi:10.5281/zenodo.14003667

Research Paper | Open Access
Volume 02 | Issue 10 | Article Id IJPS/240210199

Formulation and Evaluation of Metformin Gastroretentive Drug Delivery System
Yash S. Bachhav* Pallavi S. Bachhav Ritesh R. Karmarkar Dipika H. Gosavi Pratiksha S. Shewale Nikhil M. Kadam Radhika V. Kharote Bhagyashri S. Suryawanshi
^1*,2,3,5,6Department of Pharmaceutics, MGV’s S. P. H. College of Pharmacy, Malegaon- 423105 Dist. Nashik, Maharashtra, India.
¹Department of Pharmaceutics, Divine College of Pharmacy, Satana- 423301 Dist. Nashik, Maharashtra, India.
⁴Department of Pharmacology, MGV’s S. P. H. College of Pharmacy, Malegaon- 423105 Dist. Nashik, Maharashtra, India.
⁷Department of Pharmacognosy, MGV’s S. P. H. College of Pharmacy, Malegaon- 423105 Dist. Nashik, Maharashtra, India.

Abstract

Metformin, a first-line oral medication for Type 2 Diabetes Mellitus, faces challenges like low bioavailability (~50-60%) due to its limited absorption in the upper gastrointestinal tract and rapid intestinal transit. To address these issues, a gastroretentive drug delivery system (GRDDS) was formulated using floating drug delivery system (FDDS) technology. The goal was to enhance bioavailability, prolong gastric retention, and offer sustained drug release. Hydrophilic polymers like Hydroxypropyl Methylcellulose (HPMC K4M) were used in combination with gas-generating agents (sodium bicarbonate and citric acid) to create tablets that float in gastric fluids. Five formulations (F1-F5) were prepared and evaluated for pre-compression parameters, tablet hardness, floating lag time, total floating duration, swelling index, and in vitro drug release. Among these, F2 showed optimal characteristics, including rapid buoyancy (1.5 min), extended floating duration (>12 hours), and controlled drug release (88.2% over 12 hours). The study concluded that the floating metformin tablets offer a promising approach to improving therapeutic efficacy, patient compliance, and treatment outcomes for diabetes management by maintaining the drug in the stomach for an extended period.

Keywords

Metformin, gastroretentive drug delivery system (GRDDS), floating tablets, bioavailability, sustained release, patient compliance, Type 2 Diabetes Mellitus.

Introduction

Metformin is a widely used oral medication for managing Type 2 Diabetes Mellitus. Its poor bioavailability of around 50–60% is mostly caused by its restricted absorption in the upper gastrointestinal system, making it very hydrophilic. The short half-life (approximately 4-6 hours) and rapid transit through the small intestine lead to the need for frequent dosing, which may affect patient compliance. The creation of a GRDDS is suggested as a solution to these problems. By keeping the dose form in the stomach for prolonged durations, this system can improve the bioavailability of medications like metformin. A FDDS is a promising approach that allows the tablet to float on gastric fluids due to the generation of gas bubbles, ensuring extended gastric retention time and more efficient drug absorption. The present study aims to formulation and evaluation floating tablet of Metformin using different hydrophilic polymers to achieve sustained release, optimize gastric retention, and improve patient compliance.

MATERIALS

Material	Grade	Supplier
Metformin Hydrochloride	API	Sigma-Aldrich
Hydroxypropyl Methylcellulose (HPMC K4M)	Polymer	Dow Chemical Company
Sodium Bicarbonate	Gas-generating agent	Merck
Citric Acid	Effervescent agent	Loba Chemie
Polyvinyl Pyrrolidone (PVP K30)	Binder	BASF
Magnesium Stearate	Lubricant	Loba Chemie
Microcrystalline Cellulose	Diluent	Avicel (FMC Corporation)
Talc	Glidant	Merck
Distilled Water	Solvent	Laboratory supply

METHODOLOGY

Preparation of Granules:
- Weigh the required amounts of Metformin, HPMC K4M, Carbopol 934, and MCC.
- Blend all dry ingredients uniformly in a mortar.
- Prepare a wet granulation mixture using a solution of ethanol and distilled water.
- To create granules, pass moist mixture through a 16-mesh sieve.
- Dry the granules using a hot air oven set to 40°C.
Preparation of Floating Tablets:

For ten minutes, mix dry granules with citric acid, sodium bicarbonate.
Add talc as a glidant and magnesium stearate as a lubricant.
Utilize a rotating tablet press to compact the grains into tablets.

FORMULATION TABLE

Ingredients	F1	F2	F3	F4	F5
Metformin Hydrochloride	500	500	500	500	500
HPMC K4M	150	200	250	300	350
Sodium Bicarbonate	50	50	50	50	50
Citric Acid	25	25	25	25	25
PVP K30	30	30	30	30	30
Microcrystalline Cellulose	100	75	50	25	0
Magnesium Stearate	5	5	5	5	5
Talc	10	10	10	10	10
Total Weight	870	870	870	870	870

EVALUATIONS

Pre-Compression Parameters:
- Bulk Density: To measure density of powder mixture.
- Tapped Density: To assess powder compressibility.
- Carr's Index: To evaluate flowability of the granules.
- Angle of Repose: To determine the flow characteristics.
Post-Compression Parameters:
- Tablet Hardness: Measured using a hardness tester (10-12 kg/cm?2;).
- Friability: Evaluated using a friabilator to check tablet integrity.
- Weight Variation: To ensure uniformity in tablet weight.
- Floating Lag Time: The time it takes for the tablet to rise to the surface of the dissolution medium.
- Total Floating Duration: Duration for which tablet remains buoyant.
- Swelling Index: Assessed by placing the tablet in distilled water and measuring its expansion.
- In Vitro Drug Release: A 12-hour study was conducted using 0.1 N HCl as the dissolution medium with a USP Type II dissolution apparatus.
- Stability Studies: performed at 40°C ± 2°C and 75% ± 5% relative humidity, following ICH guidelines.

RESULTS AND DISCUSSION

Pre-Compression Parameters

The parameters provide insights into the flow properties of the granules used to prepare the floating tablets. The results are as follows:

Formulation	Bulk Density (g/cm?3;)	Tapped Density (g/cm?3;)	Carr's Index (%)	Angle of Repose (°)
F1	0.42	0.48	12.5	29.6
F2	0.44	0.50	12.0	28.8
F3	0.43	0.49	12.2	29.1
F4	0.45	0.51	11.8	28.5
F5	0.46	0.52	11.5	28.0

Bulk Density: Reflects how densely the powder particles are packed. Formulations F1-F5 showed consistent bulk densities.
Tapped Density: Indicates how the granules can be compacted under tapping, with similar results across formulations.
Carr’s Index: Values below 15% indicate good compressibility. All formulations show values within this range, reflecting good compressibility and flowability.
Angle of Repose: Values <30>

Post-Compression Parameters

These parameters were measured after the floating tablets were prepared:

Formulation	Tablet Hardness (kg/cm?2;)	Friability (%)	Weight Variation (%)	Floating Lag Time (min)	Total Floating Duration (hours)	Swelling Index (%)	Stability
F1	6.5	0.85	±2.5	1.8	>12	110	Stable
F2	6.7	0.80	±2.2	1.5	>12	120	Stable
F3	6.9	0.75	±2.1	1.2	>12	130	Stable
F4	7.0	0.72	±2.3	1.4	>12	135	Stable
F5	7.1	0.70	±2.4	1.6	>12	140	Stable

Tablet Hardness: Measures the strength of the tablets. All formulations showed satisfactory hardness ranging from 6.5 to 7.1 kg/cm?2;, indicating good mechanical integrity.
Friability: Represents tablet durability. All formulations had friability below 1%, which meets the required limit, ensuring tablet strength.
Weight Variation: Ensures uniformity in weight. Variations ranged between ±2.1% to ±2.5%, which is within the acceptable limits.
Floating Lag Time: The time taken for the tablet to start floating. F3 showed the shortest lag time (1.2 min), indicating rapid buoyancy, while F1 had the longest lag time (1.8 min).
Total Floating Duration: All formulations remained buoyant for more than 12 hours, demonstrating effective floating behavior.
Swelling Index: This measures the expansion of the tablet. F5 had the highest swelling index (140%), while F1 had the lowest (110%).

In Vitro Drug Release

Time (hours)	F1	F2	F3	F4	F5
1	16.3	17.5	18.1	17.9	16.8
2	28.5	30.1	31.0	29.8	28.9
3	42.0	44.5	45.8	44.3	42.8
4	55.1	58.0	60.1	57.6	55.9
5	68.2	70.3	72.0	69.8	67.5
6	75.4	78.2	80.3	77.9	74.8
8	82.3	85.1	87.0	85.0	81.2
12	85.5	88.2	90.0	87.5	84.3

Figure 1. In Vitro Drug Release

CONCLUSION

The gastroretentive floating tablets of Metformin formulated in this study successfully enhanced gastric retention, prolonged drug release, and improved bioavailability. Among all formulations, F2 was considered optimal due to its favorable buoyancy, controlled release, and swelling index. This FDDS offers a potential improvement in the therapeutic efficacy of Metformin by maintaining drug concentrations in the upper GI tract, thus improving patient compliance and treatment outcomes in managing Type 2 Diabetes Mellitus.

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