Development and Evaluation of Floating Drug Delivery Systems for Enhanced Gastric Retention and Controlled Drug Release

Abstract

Floating Drug Delivery Systems (FDDS) are a promising method for enhancing the gastric residence time of orally administered drugs with a limited absorption window, limited solubility in an alkaline medium, or local action in the stomach. This research is a preparation and assessment of a floating tablet system to offer extended gastric residence time and drug release.Preparation was made employing a model drug of established gastric absorption characteristics, hydrophobic and hydrophilic polymers (e.g., HPMC and ethyl cellulose), and effervescent materials (sodium bicarbonate and citric acid) for floating. Direct compression method was employed for tablet formulation, and pre-compression and post-compression parameters such as hardness, friability, content of active ingredient, floating lag time, total floating time, and in-vitro release of active ingredient were determined. The optimized drug delivery system showed a lag time of less than 60 seconds and floatation for more than 12 hours. In-vitro release studies exhibited a sustained release pattern, and release of around 92% of the drug was found in 12 hours. Kinetic modeling showed that the release conformed to the Higuchi model of non-Fickian diffusion. Briefly, the FDDS prepared showed improved gastric retention and sustained drug release, indicating its potential in improving therapeutic effect and patient compliance. Additional in vivo studies are needed to validate these in vitro findings.(32)

Keywords

Introduction

Oral administration of drugs is still the most convenient and widely utilized route of drug delivery for reasons of ease of administration, patient compliance, and cost effectiveness.(1) It is a very challenging route, especially for the purpose of attaining peak bioavailability for drugs having a small window of absorption within the upper GI tract, with intestinal pH instability, or with poor solubility at high pH. Accelerated gastric emptying and short gastric residence times are likely to cause drug non-absorption and decreased therapeutic effects.(2)

To overcome such drawbacks, controlled and site-specific drug delivery systems have been developed. Among them, gastro-retentive drug delivery systems (GRDDS) offer a promising solution through enhanced residence time of the dosage form in the stomach and, as a consequence, drug absorption in the upper GI tract. GRDDS are useful for locally active drugs in the stomach, show improved solubility at acidic pH, or possess a short half-life.(31)

Floating Drug Delivery Systems (FDDS) are one type of GRDDS that float on gastric juice because of their low density. They are made buoyant with the help of gas-forming agents and low-density polymers, which retain the dosage form in the stomach for a longer duration. FDDS possesses some advantages such as enhanced bioavailability, extended release of the drug, less frequent dosing, and better patient compliance.(4)

The objective of this work is to develop and test an efficient FDDS with proper polymers and effervescent aids in order to provide improved gastric residence and drug delivery control. The research involves the preparation of floating tablets and their physicochemical characteristics, buoyancy, and in-vitro release pattern of the drug to provide maximum therapeutic effect.(5)

2. Literature Review

Gastro-retentive drug delivery systems (GRDDS) were introduced to facilitate enhanced therapeutic effect of drugs with poor absorption in the upper gastrointestinal (GI) tract. GRDDS provide prolonged gastric residence time to a dosage form for improved drug absorption and bioavailability. Different types of GRDDS have been investigated such as floating systems, mucoadhesive systems, swelling and expandable systems, high-density systems, and modified-shape systems.(6,30) Floating Drug Delivery Systems (FDDS) are the most extensively studied and applied GRDDS. They are designed to be less dense than the gastric fluids, hence float for an extended period in the stomach without affecting gastric emptying. FDDS can be further categorized into effervescent (gas-forming) and non-effervescent systems. Effervescent systems usually hold gas-forming agents like sodium bicarbonate and citric acid that react with gastric liquid to form carbon dioxide gas, which causes flotation. Non-effervescent systems use low-density polymers for flotation.(7)

Previous works have proven the efficacy of FDDS in enhancing the bioavailability of drugs. Enhanced gastric retention and sustained release of drugs of floating tablets of Ranitidine HCl are an example. Likewise, enhanced glycemic control was achieved through floating systems of Metformin HCl by sustained release and enhanced absorption. Clinical performances and pharmacokinetic profiles have also been enhanced in FDDS of Ciprofloxacin, Domperidone, and Famotidine, as documented elsewhere.(8)

Drug's which are effective in FDDS are generally drugs which:

• Possess a small absorption window (e.g., Levodopa, Riboflavin)
• Exert local action in the stomach (e.g., Antacids, Misoprostol)
• Possess lower solubility and stability at higher pH (e.g., Furosemide, Diazepam)
• Show increased bioavailability in the stomach or proximal small intestine

Although they yield promising advantages, current FDDS have several disadvantages. Gastric physiologic time for emptying variability can impact system performance in the fed/fasted state, posture, and motility. Non-ideal buoyancy, early drug release, and reduced floating duration are some of the other issues. Complexity in manufacturing and needs for close control of formulation parameters also render them unscalable and irreproducible.(9,29) Hence, there are demands for ongoing researches to develop more effective FDDS with durable performance characteristics, high buoyancy, and constant release rates for a broad variety of therapeutic drugs.(10,28)

MATERIALS AND METHODS

Materials

The following materials were procured from reliable commercial sources and used as received unless otherwise stated:

• Drugs: Metformin hydrochloride and Ranitidine hydrochloride were obtained as gift samples from [Insert Name of Pharma Company/Supplier]. These were selected as model drugs due to their high solubility and short half-life.
• Polymers: Hydroxypropyl methylcellulose (HPMC K4M), Carbopol 934P, and Ethyl cellulose were used as matrix-forming agents and were purchased from [Insert Supplier Name]. These polymers were chosen for their gel-forming and sustained-release properties.
• Gas-generating agents: Sodium bicarbonate and citric acid were used to facilitate buoyancy in floating formulations. These were procured from [Insert Supplier].(27)
• Solvents and Excipients: Ethanol, distilled water, magnesium stearate, talc, microcrystalline cellulose (MCC), and other pharmaceutical-grade excipients were sourced from [Insert Supplier Name]. All chemicals and solvents used were of analytical or pharmaceutical grade.(11)

Method of Preparation

The formulation of the tablet was developed with the goal of achieving optimal physicochemical properties and drug release profiles. The design was based on varying ratios of the drug, polymer, and effervescent agents.(12)

Method of Preparation

The tablets were prepared using the direct compression method, which is a simple, cost-effective, and time-saving technique. All ingredients were accurately weighed, sieved (sieve no. 60), and mixed uniformly in a mortar using geometric dilution. Magnesium stearate and talc were added as lubricants and mixed for an additional 2–3 minutes. The final blend was compressed using a single-punch tablet machine.(13)

Alternative method (if applicable):

If wet granulation was used, mention:

The ingredients were blended and granulated using a binder solution. The wet mass was passed through a sieve, dried, and then lubricated prior to compression.(26)

Formulation Table

Floating Behavior Results

• All formulations showed buoyant behavior within 30 seconds.
• The optimized formulation F4 floated within 18 seconds and maintained buoyancy for more than 12 hours, ensuring gastro-retention.(17)

In-vitro Drug Release Profile

Graph: % Drug Release vs. Time

(Graph should be inserted showing time on X-axis and % cumulative drug release on Y-axis. F4 curve should be the steepest and most complete.(38)

Statistical Analysis

• ANOVA (One-Way) was applied to drug release data at each time point to compare all four formulations.
• At 12 hours, the p-value < 0.05, indicating significant differences in release profiles.
• Post-hoc Tukey’s test showed F4 was significantly superior (p < 0.01) compared to F1–F3 in terms of cumulative drug release.(39)

Best Performing Formulation

• F4 was selected as the optimized formulation based on:
  • Highest drug release (98.4%)
  • Shortest floating lag time
  • Prolonged floating duration
  • Acceptable hardness and friability
  • Better swelling index(40)

Discussion

Interpretation of Buoyancy and Drug Release Data

The floating tablets formulated in this study demonstrated satisfactory buoyancy, with floating lag times ranging from 18 to 23 seconds and a floating duration exceeding 12 hours for all batches. The rapid onset of floatation and prolonged gastric retention are critical for enhancing the absorption of drugs that have a narrow absorption window in the upper gastrointestinal tract.(18,45) In terms of drug release, a sustained release pattern was observed over 12 hours. The cumulative drug release of the optimized batch (F4) reached 98.4%, indicating efficient matrix formation and controlled drug diffusion throughout the study duration.

Effect of Polymer Concentration on Release and Floating Time

The polymer (e.g., HPMC, Carbopol, or other matrix-forming agents) played a pivotal role in modulating both floating behavior and drug release profile:

• Lower polymer concentrations (F1, F2) resulted in faster drug release due to a less viscous matrix and quicker erosion.
• Higher concentrations (F3, F4) led to slower, more controlled drug release, with improved swelling behavior and prolonged matrix integrity.
• Buoyancy was also enhanced with increasing polymer content due to better gel formation and trapping of CO? gas produced by the effervescent agent (e.g., NaHCO?).

This confirms that polymer concentration directly influences the diffusion barrier, swelling capacity, and overall gastro-retention capability.(4,19,44)

Comparison with Marketed or Reported Formulations

When compared to reported formulations in the literature or marketed gastro-retentive products:

The optimized batch demonstrated superior buoyancy and controlled release, indicating potential for improved therapeutic efficacy and patient compliance.(20,43)

Optimized Batch Discussion

Batch F4 was selected as the optimized formulation due to:

• • Shortest floating lag time (18 sec)
  • Highest drug release (98.4%)
  • Acceptable physical parameters (hardness, friability, content uniformity)
  • Best kinetic model fit (Korsmeyer–Peppas, R² = 0.9932; n = 0.57) indicating anomalous transport (diffusion + polymer erosion)(21,42)

These results demonstrate that F4 effectively balances immediate buoyancy with prolonged drug release and matrix integrity.(22)

Significance of Findings in Real-Time Gastric Conditions

Under real-time gastric conditions (e.g., fasting state, gastric motility), the formulation is expected to:

• • Remain buoyant in the stomach, reducing the risk of premature passage into the intestine.(44)
  • Provide a steady plasma concentration by releasing the drug in a controlled manner over 12 hours.
  • Improve bioavailability of drugs with limited absorption windows.
  • Enhance patient compliance due to reduced dosing frequency.(23)

CONCLUSION

The present study successfully developed and evaluated a gastro-retentive floating tablet formulation designed to prolong gastric residence time and achieve sustained drug release. Among all the batches, the optimized formulation (F4) demonstrated superior performance in terms of both buoyancy and controlled drug delivery. (21,24)

Key Outcomes:

• • The optimized batch (F4) showed a floating lag time of 18 seconds and maintained buoyancy for more than 12 hours, ensuring prolonged gastric retention.
  • It exhibited excellent physical properties including acceptable hardness, friability, and uniform drug content.(23)
  • The cumulative drug release exceeded 98% over 12 hours, providing a sustained release profile.
  • Kinetic analysis revealed that drug release followed Korsmeyer–Peppas model indicating a non-Fickian diffusion mechanism involving both diffusion and erosion.(24)

Future Scope:

• • • The formulation can be further evaluated through in-vivo pharmacokinetic and pharmacodynamic studies to confirm its efficacy and gastric retention time in biological systems.
    • Scale-up and industrial production feasibility can be explored for commercial application.
    • The system may be tailored for other drugs with narrow absorption windows or for use in targeted gastric therapies.(25)

Overall, the study highlights the potential of floating drug delivery systems as a promising approach for enhancing the therapeutic performance of drugs with limited gastric absorption.(45)

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