Fabrication of Gastroretentive and Extended-Release Famotidine Floating Tablets via Fused Deposition Modeling

Abstract

Famotidine suffers from low oral bioavailability due to poor aqueous solubility, short half-life, and limited gastric retention. This study aimed to develop gastro-retentive floating tablets of famotidine using hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing approach to enhance its solubility, prolong gastric residence, and achieve extended drug release. Famotidine was incorporated into various polymeric carriers, including hydroxypropyl cellulose (HPC LF) and hydroxypropyl methylcellulose (HPMC E5), to produce drug-loaded filaments using an 11 mm twin-screw co-rotating extruder. The filaments were subsequently 3D-printed into low-density, hollow tablets to achieve prolonged gastric floatation. The solid-state characterization by differential scanning calorimetry (DSC) revealed the absence of famotidine’s crystalline melting peak in both filaments and 3D-printed tablets, suggesting amorphization within the polymer matrix. FTIR spectroscopy indicated hydrogen bonding interactions between famotidine and polymer hydroxyl groups, supporting the stabilization of the solid dispersion. The lead formulation demonstrated excellent buoyancy of about nine hours and extended drug release in 0.1 N HCl, confirming the potential of the system for extended gastric retention. This work highlights the utility of HME-FDM 3D printing for developing tailored, gastro-retentive dosage forms that enhance the performance of poorly soluble drugs like famotidine through amorphous solid dispersion and formulation-driven design.

Introduction

Famotidine is a potent histamine H2-receptor antagonist (H2RA) that competitively binds to the H2-receptors located on the basolateral membrane of gastric parietal cells, thereby inhibiting histamine-stimulated gastric acid secretion. Famotidine is widely used for the treatment of acid-related gastrointestinal disorders, including gastric and duodenal ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome. Its therapeutic effect is primarily achieved by reducing both the concentration and volume of gastric acid secretions [1,2,3]. However, the oral delivery of famotidine presents several challenges, including poor water solubility (0.271 mg/mL) [4], relatively short biological half-life (2.5—3.5 h), low and variable oral bioavailability (approximately 40–45%), and inconsistent absorption due to variations in gastrointestinal transit and gastric retention time (GRT) [5]. Additionally, famotidine is associated with adverse effects such as headache, dizziness, and diarrhea [6]. These limitations make famotidine an ideal candidate for the development of extended-release formulations designed to prolong gastric residence, enhance bioavailability, reduce dosing frequency, and minimize systemic side effects [7].

Gastro-retentive drug delivery systems (GRDDS) are advanced formulations designed to prolong the residence time of a drug in the stomach, thereby enabling extended drug release and improved bioavailability [8]. By maintaining the drug in the upper gastrointestinal tract for extended periods, GRDDS help achieve more consistent plasma concentrations, which in turn reduce pharmacokinetic variability, dosing frequency, and the incidence of adverse effects, all of which contribute to improved patient compliance [9, 10]. Various strategies have been developed to achieve gastric retention, including floating systems, expandable systems, magnetic, raft-forming, ion-exchanging, high-density formulations, and bioadhesives [11].

Floating drug delivery systems (FDDS), a prominent type of GRDDS, are characterized by their low density, which provides sufficient buoyancy to allow the dosage form to float in the gastric area and remain in the stomach for an extended period [12, 13]. As the system floats in the gastric contents, the drug is released slowly at the desired rate, which results in prolonged gastro-retention time and reduced fluctuations in drug absorption. FDDS offer numerous advantages, particularly for drugs that are highly soluble at low pH, act locally in the stomach, or are primarily absorbed in the upper gastrointestinal tract [14]. They are also beneficial for drugs that are unstable or poorly absorbed in the lower GI tract, or for minimizing systemic side effects by limiting drug exposure beyond the stomach. Owing to these attributes, FDDS are considered effective site-specific delivery systems for a range of therapeutic applications [15,16,17,18]. FDDS can be classified into effervescent systems, which generate carbon dioxide via gas-forming agents such as sodium bicarbonate, but may cause gastrointestinal discomfort due to gas production; and non-effervescent systems, which achieve floatation through the use of inherently low-density materials and tend to be better tolerated [19].

Previous studies have explored the development of gastro-retentive famotidine formulations using various polymeric systems and manufacturing techniques. For instance, semisolid extrusion 3D printing has been employed to fabricate floating tablets incorporating hydroxypropyl methylcellulose (HPMC), achieving buoyancy for up to 10 h [19]. In another approach, superporous hydrogel tablets composed of polymers such as chitosan, sodium alginate, and pectin were developed via direct compression. While these systems sustained drug release for up to 12 h and the tablets were characterized for porosity and density, their actual buoyancy was not assessed, which is an essential parameter for establishing effective gastro-retentive behavior [20].

Hot-melt extrusion (HME) has emerged as a versatile and solvent-free processing technology widely used in the pharmaceutical industry for enhancing the performance of active pharmaceutical ingredients (APIs) [21,22,23]. Originally developed for producing solid dispersions, HME enables the incorporation of APIs into various polymer and lipid matrices to improve solubility, stability, and controlled release characteristics. Its applications now extend to a broad range of dosage forms, including extended-release formulations [24], films [25], implants [26], microencapsulation systems [27], taste-masked products [28], nanotechnology platforms [29], and floating drug delivery systems. The physicochemical and mechanical properties of extrudates are highly dependent on critical processing and formulation parameters such as barrel temperature, screw speed, feeding rate, and the rheological behavior of the input materials.

In parallel, three-dimensional (3D) printing—particularly fused deposition modeling (FDM) allows for the precise fabrication of individualized dosage forms with customized geometry, size, and drug release profiles [30]. Its potential to produce small-batch, patient-tailored medications makes it especially viable for personalized medicine applications [31]. Recent studies have demonstrated the utility of FDM in creating various gastro-retentive platforms, including floating aid devices [32], floating pulsatile tablets [33], and controlled-release floating matrices [34, 35].

Notably, the integration of HME with FDM offers a unique opportunity to combine the advantages of both technologies. HME can be used to prepare drug-loaded filaments with improved drug-polymer miscibility and mechanical strength, which are then fed into the FDM printer to fabricate precise, customizable dosage forms. This hybrid approach enables the design of floating systems with controlled drug load and particular geometry optimized for buoyancy and tailored drug release kinetics. Despite its promise, the application of HME-FDM integration in the development of floating drug delivery systems for drugs like famotidine remains largely unexplored, underscoring the need for further investigation.

Certain limitations are associated with existing FDDS development methods. Gas-generating tablets can cause gastrointestinal discomfort and are dependent on gastric pH for buoyancy. Directly compressed hydrophilic matrix tablets often suffer from an initial burst release followed by declining release rates, and may require complex multilayer or core-in-cup designs to control release [36]. Complex geometries are known to be challenging to achieve by conventional manufacturing processes. While 3D-printed tablets can incorporate complex geometries and offer the potential for personalization, semisolid extrusion (SSE) methods often yield tablets with poor resolution and limited geometric precision. FDM-based approach may address these challenges by eliminating the need for gas-generation, enabling high-resolution geometric control without complex manufacturing steps, and allowing CAD-driven customization of tablet size, dose, and buoyancy for personalized gastro-retentive therapy.

Thus, the present research aims to develop a gastro-retentive floating tablet of famotidine utilizing FDM 3D printing technology. To achieve this, the dual combination of hydroxypropyl cellulose (HPC LF) and hydroxypropyl methylcellulose (HPMC E5) as a co-carrier matrix was employed. These materials were systematically investigated for their suitability to produce drug-loaded filaments with optimal mechanical strength and printability. By tailoring the tablet’s internal geometry through the infill density and sealed hollow design, the printed units were capable of achieving immediate and consistent buoyancy and extended drug release, offering a promising approach to enhance famotidine’s gastric retention and therapeutic efficacy.

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Materials

Famotidine (purity 98.8%) was obtained from Thermo Fisher Scientific (Waltham, MA, USA). Hydroxypropyl cellulose grade LF (Klucel™ HPC-LF) was kindly provided by Ashland Inc. (Wilmington, DE, USA). Hydroxypropyl methylcellulose (Methocel™ HPMC-E5) was gifted, and ethylcellulose (Ethocel™ N.F. Premium) was purchased from the Dow Chemical Company (Midland, MI, USA). All other analytical grade chemicals and solvents were purchased from Fisher Scientific (Hanover Park, IL, USA).

Al Shawakri, E., Ashour, E.A., Elkanayati, R.M. et al. Fabrication of Gastroretentive and Extended-Release Famotidine Floating Tablets via Fused Deposition Modeling. AAPS PharmSciTech 26, 240 (2025). https://doi.org/10.1208/s12249-025-03237-x

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