Glycerol-Enhanced Slot-Die Coated Films: A New Era for Buccal Drug Delivery
Films were produced using the Research Laboratory Coater equipped with a slot-die head, ensuring precision and scalability.
A new study by Pantazoglou et al., published in Molecular Pharmaceutics, investigates how glycerol enhances the performance of pectin-based buccal films. Using slot-die coating, a novel manufacturing technique, researchers have developed customizable films that adhere to the buccal mucosa, release drugs in a controlled manner, and remain safe for human use. This innovation addresses challenges in oral drug delivery, offering a scalable solution for rapid or prolonged therapeutic needs. Buccal delivery—via the mucosal tissues of the mouth—provides an efficient pathway for drug absorption into systemic circulation. This method bypasses the gastrointestinal (GI) tract, avoiding drug degradation and improving bioavailability. However, traditional manufacturing methods like solvent casting face scalability and consistency issues. Slot-die coating not only solves these problems but also allows fine-tuning of drug delivery properties.
Key Highlights:
Innovative Drug Delivery: Buccal films utilizing pectin and glycerol offer a patient-friendly alternative to oral and parenteral drug administration.
Enhanced Compliance: Designed to cater to the needs of elderly patients, children, and individuals with swallowing difficulties (dysphagia).
Precision Fabrication: Films were created using slot-die coating, ensuring consistent thickness and high-quality production.
Drug Release Optimization: Glycerol content influences drug release rates, with glycerol-free films (GLY0) releasing 95% of paracetamol in 60 minutes, compared to 74% for films with 20% glycerol (GLY20).
Superior Mucoadhesion: Films with higher glycerol content exhibit stronger adhesion to mucosal surfaces, enhancing drug retention and absorption.
Enhanced Permeability: GLY20 films doubled paracetamol permeation through porcine buccal mucosa in the first 120 minutes compared to GLY0 films.
Comprehensive Characterization: Advanced methods like Quartz Crystal Microbalance with Dissipation (QCM-D) and an open-source force analyzer provided detailed insights into mucoadhesion and film properties.
Biocompatibility and Flexibility: All films demonstrated excellent biocompatibility, with adjustable disintegration and drug release rates tailored to therapeutic needs.
Promising Applications: These user-friendly films are ideal for efficient, targeted drug delivery, particularly in scenarios requiring controlled release profiles.
The Research Laboratory Coater with a Slot-die Head and Syringe Pump.
Study Background: Why Slot-Die Coating is Key to Scalable Buccal Films
Oral administration is the most common drug delivery route, but it has limitations, particularly for drugs that degrade in the stomach or intestines. Buccal drug delivery offers a promising alternative, with benefits including rapid absorption, bypassing the GI tract, and ease of use for patients like children or the elderly.
Pectin, a biopolymer derived from plant cell walls, is known for its mucoadhesive properties and biocompatibility. By combining pectin with glycerol—a plasticizer that enhances flexibility and interaction with mucosal surfaces—the researchers aimed to develop films with customizable drug release and strong mucoadhesion. The study used paracetamol as a model drug to evaluate film performance.
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Slot-die coating allows precise control of film thickness and composition, ensuring uniform, scalable manufacturing.
Methods: Slot-Die Coating and Glycerol’s Role in Buccal Film Fabrication
To fabricate and evaluate the films, the researchers followed these steps:
Film Fabrication: Using slot-die coating, pectin solutions with varying glycerol concentrations (0%, 5%, 10%, and 20%) were cast onto substrates, dried, and cut into uniform 1 × 1 cm films.
Physicochemical Characterization: Film thickness, surface morphology (via SEM), and mechanical properties were analyzed.
Drug Release and Permeability: Drug release profiles were measured in phosphate-buffered saline, while permeability was tested using porcine buccal mucosa.
Mucoadhesion Testing: Quartz crystal microbalance with dissipation (QCM-D) and a force analyzer assessed the films’ adhesion to artificial mucosal surfaces.
Biocompatibility Assessments: Cytotoxicity was evaluated using human buccal cells exposed to the film formulations.
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Results: Slot-Die Coating Enhances Film Adhesion, Permeability, and Drug Release
The study revealed several significant findings:
Film Properties:
Glycerol improved flexibility, adhesion, and thickness, resulting in films that were easy to handle.
Higher glycerol concentrations (20%) delayed film disintegration, making them suitable for prolonged drug release.
Mucoadhesion:
Films with 20% glycerol showed the strongest mucoadhesion, attributed to the enhanced mobility of polymer chains and improved interaction with mucosal surfaces.
Drug Release:
Glycerol-modified films exhibited slower, controlled drug release. Films with 20% glycerol released paracetamol over 140 minutes, compared to 60 minutes for glycerol-free films.
Permeability:
Films containing 20% glycerol doubled the permeability of paracetamol through porcine buccal mucosa within the first 120 minutes, compared to glycerol-free films.
Biocompatibility:
All films were safe for human buccal cells, with only minor reductions in cell viability observed at higher glycerol concentrations.
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Glycerol improves film flexibility, enhances mucoadhesion, and slows drug release for sustained therapeutic effects.
Discussion: The Impact of Slot-Die Coating on Buccal Film Performance
This study underscores the potential of glycerol as both a plasticizer and a functional enhancer for buccal films. By increasing polymer flexibility and creating a denser, more interactive film matrix, glycerol improves mucoadhesion and permeability. The delayed drug release observed with higher glycerol levels suggests that these films can be tailored to meet specific therapeutic needs, such as sustained-release formulations.
The use of slot-die coating further enhances the scalability of this technology, ensuring consistent film quality and making it viable for large-scale production. These findings open the door to more accessible and customizable drug delivery options for various patient demographics.
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Conclusion: Slot-Die Coating as the Future of Buccal Drug Delivery
Pantazoglou et al.’s study highlights a significant advancement in pharmaceutical technology. By leveraging glycerol’s properties and the precision of slot-die coating, the researchers developed scalable, effective buccal films capable of meeting diverse drug delivery requirements. This innovative approach addresses both manufacturing and functional challenges, paving the way for more reliable and patient-friendly drug delivery systems.
Authors
Eleftheria Pantazoglou
Matteo Tollemeto
Nazanin Zanjanizadeh Ezazi
Tien-Jen Chang
Leticia Hosta Rigau
Jette Jacobsen
Line Hagner Nielsen
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