Design and Evaluation of New Gel-Based Floating Matrix Tablets Utilizing the Sublimation Technique for Gastroretentive Drug Delivery.

A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release.

pH-responsive chitosan-mediated spherical mesoporous silica microspheres for high loading and controlled delivery of 5-Fluorouracil.

The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 µm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.

Neuro-fuzzy model for predicting insulin delivery from crosslinked agar-carbomer hydrogels.

This study focuses on the innovation of an inhaled sustained release form of insulin and the development of a neuro-fuzzy model specifically tailored to predict insulin release kinetics from polycondensed agar-carbomer hydrogels. These were synthesized by blending agar and carbomer, incorporating propylene glycol and glycerol, and then cross-linking by polycondensation. The structure and morphology of the hydrogel were analyzed via Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy and Proton Nuclear Magnetic Resonance Spectroscopy. The neuro-fuzzy model, a combination of artificial neural networks and fuzzy logic, employs inputs such as concentrations of crosslinking agents, polycondensation time, and release time, with the output being the rate of insulin release. The model demonstrated a strong correlation with experimental data, highlighting its effectiveness and precision in predicting insulin delivery from hydrogel compositions and temporal parameters. This emphasizes the importance of intelligent modelling for forecasting the kinetic release of therapeutic agents from novel drug delivery systems.

Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration.

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-ß1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-ß1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

A Nanocomposite Dynamic Covalent Cross-Linked Hydrogel Loaded with Fusidic Acid for Treating Antibiotic-Resistant Infected Wounds.

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with high levels of morbidity and is considered a difficult-to-treat infection, often requiring nonstandard treatment regimens and antibiotics. Since over 40% of the emerging antibiotic compounds have insufficient solubility that limits their bioavailability and thus efficacy through oral or intravenous administration, it is crucial that alternative drug delivery products be developed for wound care applications. Existing effective treatments for soft tissue MRSA infections, such as fusidic acid (FA), which is typically administered orally, could also benefit from alternative routes of administration to improve local efficacy and bioavailability while reducing the required therapeutic dose. Herein, we report an antimicrobial poly(oligoethylene glycol methacrylate) (POEGMA)-based composite hydrogel loaded with fusidic acid-encapsulating self-assembled polylactic acid-b-poly(oligo(ethylene glycol) methyl ether methacrylate) (PLA-POEGMA) nanoparticles for the treatment of MRSA-infected skin wounds. The inclusion of the self-assembled nanoparticles (380 nm diameter when loaded with fusidic acid) does not alter the favorable mechanical properties and stability of the hydrogel in the context of its use as a wound dressing, while fusidic acid (FA) can be released from the hydrogel over ∼10 h via a diffusion-controlled mechanism. The antimicrobial studies demonstrate a clear zone of inhibition in vitro and a 1-2 order of magnitude inhibition of bacterial growth in vivo in an MRSA-infected full-thickness excisional murine wound model even at very low antibiotic doses. Our approach thus can both circumvent challenges in the local delivery of hydrophobic antimicrobial compounds and directly deliver antimicrobials into the wound to effectively combat methicillin-resistant infections using a fraction of the drug dose required using other clinically relevant strategies.

Ultrasound-mediated nano-sized drug delivery systems for cancer treatment: Multi-scale and multi-physics computational modeling.

Computational modeling enables researchers to study and understand various complex biological phenomena in anticancer drug delivery systems (DDSs), especially nano-sized DDSs (NSDDSs). The combination of NSDDSs and therapeutic ultrasound (TUS), that is, focused ultrasound and low-intensity pulsed ultrasound, has made significant progress in recent years, opening many opportunities for cancer treatment. Multiple parameters require tuning and optimization to develop effective DDSs, such as NSDDSs, in which mathematical modeling can prove advantageous. In silico computational modeling of ultrasound-responsive DDS typically involves a complex framework of acoustic interactions, heat transfer, drug release from nanoparticles, fluid flow, mass transport, and pharmacodynamic governing equations. Owing to the rapid development of computational tools, modeling the different phenomena in multi-scale complex problems involved in drug delivery to tumors has become possible. In the present study, we present an in-depth review of recent advances in the mathematical modeling of TUS-mediated DDSs for cancer treatment. A detailed discussion is also provided on applying these computational models to improve the clinical translation for applications in cancer treatment. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Critical Design Strategies Supporting Optimized Drug Release from Polymer-Drug Conjugates.

The importance of an adequate linking moiety design that allows controlled drug(s) release at the desired site of action is extensively studied for polymer-drug conjugates (PDCs). Redox-responsive self-immolative linkers bearing disulfide moieties (SS-SIL) represent a powerful strategy for intracellular drug delivery; however, the influence of drug structural features and linker-associated spacers on release kinetics remains relatively unexplored. The influence of drug/spacer chemical structure and the chemical group available for conjugation on drug release and the biological effect of resultant PDCs is evaluated. A "design of experiments" tool is implemented to develop a liquid chromatography-mass spectrometry method to perform the comprehensive characterization required for this systematic study. The obtained fit-for-purpose analytical protocol enables the quantification of low drug concentrations in drug release studies and the elucidation of metabolite presence. and provides the first data that clarifies how drug structural features influence the drug release from SS-SIL and demonstrates the non-universal nature of the SS-SIL. The importance of rigorous linker characterization in understanding structure-function correlations between linkers, drug chemical functionalities, and in vitro release kinetics from a rationally-designed polymer-drug nanoconjugate, a critical strategic crafting methodology that should remain under consideration when using a reductive environment as an endogenous drug release trigger.

Long-Acting Ocular Injectables: Are We Looking In The Right Direction?

The complex anatomy and physiological barriers of the eye make delivering ocular therapeutics challenging. Generally, effective drug delivery to the eye is hindered by rapid clearance and limited drug bioavailability. Biomaterial-based approaches have emerged to enhance drug delivery to ocular tissues and overcome existing limitations. In this review, some of the most promising long-acting injectables (LAIs) in ocular drug delivery are explored, focusing on novel design strategies to improve therapeutic outcomes. LAIs are designed to enable sustained therapeutic effects, thereby extending local drug residence time and facilitating controlled and targeted drug delivery. Moreover, LAIs can be engineered to enhance drug targeting and penetration across ocular physiological barriers.

Harnessing the power of biological macromolecules in hydrogels for controlled drug release in the central nervous system: A review.

Hydrogels have immense potential in revolutionizing central nervous system (CNS) drug delivery, improving outcomes for neurological disorders. They serve as promising tools for controlled drug delivery to the CNS. Available hydrogel types include natural macromolecules (e.g., chitosan, hyaluronic acid, alginate), as well as hybrid hydrogels combining natural and synthetic polymers. Each type offers distinct advantages in terms of biocompatibility, mechanical properties, and drug release kinetics. Design and engineering considerations encompass hydrogel composition, crosslinking density, porosity, and strategies for targeted drug delivery. The review emphasizes factors affecting drug release profiles, such as hydrogel properties and formulation parameters. CNS drug delivery applications of hydrogels span a wide range of therapeutics, including small molecules, proteins and peptides, and nucleic acids. However, challenges like limited biodegradability, clearance, and effective CNS delivery persist. Incorporating 3D bioprinting technology with hydrogel-based CNS drug delivery holds the promise of highly personalized and precisely controlled therapeutic interventions for neurological disorders. The review explores emerging technologies like 3D bioprinting and nanotechnology as opportunities for enhanced precision and effectiveness in hydrogel-based CNS drug delivery. Continued research, collaboration, and technological advancements are vital for translating hydrogel-based therapies into clinical practice, benefiting patients with CNS disorders. This comprehensive review article delves into hydrogels for CNS drug delivery, addressing their types, design principles, applications, challenges, and opportunities for clinical translation.

Integrating Therapeutic Ultrasound With Nanosized Drug Delivery Systems in the Battle Against Cancer.

Controlled, localized, and timely activation of nanosized drug delivery systems (NSDDSs), using an external stimulus such as therapeutic ultrasound (TUS), can improve the efficacy of cancer treatments compared to either conventional chemotherapy methods or passive NSDDSs alone. Specifically, TUS induces thermal and mechanical effects that trigger drug release from NSDDSs and overcomes drug delivery barriers in tumor microenvironments to allow nanoparticle drug carriers to penetrate more deeply into tumor tissue while minimizing side effects. This review highlights recent advancements, contemplates future prospects, and addresses challenges in using TUS-mediated NSDDSs for cancer treatment, encompassing preclinical and clinical applications.

Numerical Mechanistic Modelling of Drug Release from Solvent-Removal Zein-Based In Situ Gel.

The development of effective drug delivery systems remains a focus of extensive research to enhance therapeutic outcomes. Among these, in situ forming gels (ISG) have emerged as a promising avenue for controlled drug release. This research focuses on the mathematical modeling of levofloxacin HCl (Lv) release from zein-based ISG using the cup method, aiming to mimic the environment of a periodontal pocket. The drug release behavior of the ISGs was investigated through experimental observations and numerical simulations employing forward and central difference formula. Notably, the experimental data for drug release from the 20% w/w zein-based ISG formulations closely aligned with the simulations obtained from numerical mechanistic modeling. In summary, 20% w/w zein-based ISG formulations demonstrated nearly complete drug release with the maximum drug concentration at the edge of the matrix phase values consistently around 100-105%, while 25% w/w zein-based ISG formulations exhibited somewhat lower drug release extents, with values ranging from 70-90%. Additionally, the rate of drug transport from the polymer matrix to the external phase influenced initial release rates, resulting in a slower release. The utilization of glycerol formal as a solvent extended drug release further than dimethyl sulfoxide, thanks to denser matrices formed by high-loading polymers that acted as robust barriers to solvent removal and drug diffusion. Furthermore, UV-vis imaging was utilized to visualize the matrix formation process and solvent diffusion within the ISGs. The imaging results offered valuable insights into the matrix formation kinetics, controlled drug release mechanisms, and the influence of solvent properties on drug diffusion. The combination of mathematical modeling and experimental visualization provides a comprehensive understanding of drug release from zein-based ISGs and offers a foundation for tailored drug delivery strategies.

Guar-Based Injectable Hydrogel for Drug Delivery and In Vitro Bone Cell Growth.

Injectable hydrogels offer numerous advantages in various areas, which include tissue engineering and drug delivery because of their unique properties such as tunability, excellent carrier properties, and biocompatibility. These hydrogels can be administered with minimal invasiveness. In this study, we synthesized an injectable hydrogel by rehydrating lyophilized mixtures of guar adamantane (Guar-ADI) and poly-ß-cyclodextrin (p-ßCD) in a solution of phosphate-buffered saline (PBS) maintained at pH 7.4. The hydrogel was formed via host-guest interaction between modified guar (Guar-ADI), obtained by reacting guar gum with 1-adamantyl isocyanate (ADI) and p-ßCD. Comprehensive characterization of all synthesized materials, including the hydrogel, was performed using nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and rheology. The in vitro drug release study demonstrated the hydrogel's efficacy in controlled drug delivery, exemplified by the release of bovine serum albumin (BSA) and anastrozole, both of which followed first-order kinetics. Furthermore, the hydrogel displayed excellent biocompatibility and served as an ideal scaffold for promoting the growth of mouse osteoblastic MC3T3 cells as evidenced by the in vitro biocompatibility study.

Sulfonated Polyether Ketone Membranes Embedded with Nalidixic Acid-An Emerging Controlled Drug Releaser.

The effective administration of medication has advanced over decades, but the medical community still faces significant demand. Burst release and inadequate assimilation are major drawbacks that affect wound healing efficiency, leading to therapy failure. The widespread application of polymers in biomedical research is significant. The polyether ether ketone (PEEK) family is known for its biocompatibility, inertness, and semi-crystalline thermoplastic properties. In our present studies, we have chosen a member of this family, polyether ketone (PEK), to explore its role as a drug carrier. The PEK backbone was subjected to sulfonation to increase its hydrophilicity. The response surface methodology (RSM) was used to optimize the sulfonation process based on the time, degree of sulfonation, and temperature. The PEK polymer was sulfonated using sulfuric acid at 150 °C for 6 h; back titration was performed to quantify the degree of sulfonation, with 69% representing the maximum sulfonation. SPEK and nalidixic sodium salt were dissolved in dichloroacetic acid to create a thin membrane. The physiological and morphological properties were assessed for the SPEK membrane. The studies on drug release in distilled water and a simulated body fluid over the course of 24 h revealed a controlled, gradual increase in the release rate, correlating with a mathematical model and demonstrating the zero-order nature of the drug release. Hemolysis on the SPEK membrane revealed lower toxicity. The SPEK membrane's biocompatibility was established using in vitro cytotoxicity tests on the Vero (IC50: 137.85 g/mL) cell lines. These results confirm that the SPEK membranes are suitable for sustained drug release.

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies.

This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of -126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.

A review on the treatment of intimal hyperplasia with perivascular medical devices: role of mechanical factors and drug release kinetics.

INTRODUCTION: Intimal hyperplasia (IH) is a significant factor limiting the success of revascularization surgery for blood flow restoration. IH results from a foreign body response and mechanical disparity that involves complex biochemical reactions resulting in graft failure. The available treatment option utilizes either different pharmacological interventions or mechanical support to the vascular grafts with limited success. AREAS COVERED: This review explains the pathophysiology of IH, responsible mechanical and biological factors, and treatment options, emphasizing perivascular devices. They are designed to provide mechanical support and pharmacology actions. The perivascular drug delivery concept has successfully demonstrated efficacy in various animal studies. Accurate projections of drug release mechanisms using mathematical modeling could be used to formulate prolonged drug elution devices. Numerical modeling aspects for the prediction of design outcomes have been given due importance that fulfills the unmet clinical need for better patient care. EXPERT OPINION: IH could be effectively prevented by simultaneous mechanical scaffolding and sustained local drug delivery. Future perivascular medical devices could be designed to integrate these essential features. Numerical modeling for device performance prediction should be utilized in the development of next-generation perivascular devices.

Magnetic-Responsive Liposomal Hydrogel Membranes for Controlled Release of Small Bioactive Molecules-An Insight into the Release Kinetics.

This work explores the unique features of magnetic-responsive hydrogels to obtain liposomal hydrogel delivery platforms capable of precise magnetically modulated drug release based on the mechanical responses of these hydrogels when exposed to an external magnetic field. Magnetic-responsive liposomal hydrogel delivery systems were prepared by encapsulation of 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) multilayered vesicles (MLVs) loaded with ferulic acid (FA), i.e., DPPC:FA liposomes, into gelatin hydrogel membranes containing dispersed iron oxide nanoparticles (MNPs), i.e., magnetic-responsive gelatin. The FA release mechanisms and kinetics from magnetic-responsive liposomal gelatin were studied and compared with those obtained with conventional drug delivery systems, e.g., free liposomal suspensions and hydrogel matrices, to access the effect of liposome entrapment and magnetic field on FA delivery. FA release from liposomal gelatin membranes was well described by the Korsmeyer-Peppas model, indicating that FA release occurred under a controlled diffusional regime, with or without magnetic stimulation. DPPC:FA liposomal gelatin systems provided smoother controlled FA release, relative to that obtained with the liposome suspensions and with the hydrogel platforms, suggesting the promising application of liposomal hydrogel systems in longer-term therapeutics. The magnetic field, with low intensity (0.08 T), was found to stimulate the FA release from magnetic-responsive liposomal gelatin systems, increasing the release rates while shifting the FA release to a quasi-Fickian mechanism. The magnetic-responsive liposomal hydrogels developed in this work offer the possibility to magnetically activate drug release from these liposomal platforms based on a non-thermal related delivery strategy, paving the way for the development of novel and more efficient applications of MLVs and liposomal delivery systems in biomedicine.

Tunable Drug Release Rate Using Modular Oral Dosage Forms.

Oral dosage forms with adjustable drug release profiles were prepared using progesterone (PGR) as a poorly-soluble model drug. The dosage forms were made as stack assemblies of functional modules. The modules were made as PGR-carrying HPMC films cut into wafer-like circular pieces. Two types of modules were used in the study; one exhibited comparatively fast drug release and the other slow release. The fast vs. slow release of each type of film utilized resulted from the grade of HPMC used in each case. Drug loading in the assembly was controlled through the total number of modules. By adjusting the proportions of the two types of modules, it is possible to fine-tune the drug release rate of the multi-layer assemblies to a wide range of profiles, bracketed between a high and low end, corresponding to the inherently fastest or slowest release obtainable with the specific materials and procedures employed. This procedure is suitable for adjusting the spring-and-parachute parameters for enhancing/optimizing the bioavailability of poorly-soluble drugs, and for developing patient-centric formulations.

A spatiotemporal computational model of focused ultrasound heat-induced nano-sized drug delivery system in solid tumors.

Focused Ultrasound (FUS)-triggered nano-sized drug delivery, as a smart stimuli-responsive system for treating solid tumors, is computationally investigated to enhance localized delivery of drug and treatment efficacy. Integration of thermosensitive liposome (TSL), as a doxorubicin (DOX)-loaded nanocarrier, and FUS, provides a promising drug delivery system. A fully coupled partial differential system of equations, including the Helmholtz equation for FUS propagation, bio-heat transfer, interstitial fluid flow, drug transport in tissue and cellular spaces, and a pharmacodynamic model is first presented for this treatment approach. Equations are then solved by finite element methods to calculate intracellular drug concentration and treatment efficacy. The main objective of this study is to present a multi-physics and multi-scale model to simulate drug release, transport, and delivery to solid tumors, followed by an analysis of how FUS exposure time and drug release rate affect these processes. Our findings not only show the capability of model to replicate this therapeutic approach, but also confirm the benefits of this treatment with an improvement of drug aggregation in tumor and reduction of drug delivery in healthy tissue. For instance, the survival fraction of tumor cells after this treatment dropped to 62.4%, because of a large amount of delivered drugs to cancer cells. Next, a combination of three release rates (ultrafast, fast, and slow) and FUS exposure times (10, 30, and 60 min) was examined. Area under curve (AUC) results show that the combination of 30 min FUS exposure and rapid drug release leads to a practical and effective therapeutic response.

Release Kinetics of Metronidazole from 3D Printed Silicone Scaffolds for Sustained Application to the Female Reproductive Tract.

Sustained vaginal administration of antibiotics or probiotics has been proposed to improve treatment efficacy for bacterial vaginosis. 3D printing has shown promise for development of systems for local agent delivery. In contrast to oral ingestion, agent release kinetics can be fine-tuned by the 3D printing of specialized scaffold designs tailored for particular treatments while enhancing dosage effectiveness via localized sustained release. It has been challenging to establish scaffold properties as a function of fabrication parameters to obtain sustained release. In particular, the relationships between scaffold curing conditions, compressive strength, and drug release kinetics remain poorly understood. This study evaluates 3D printed scaffold formulation and feasibility to sustain the release of metronidazole, a commonly used antibiotic for BV. Cylindrical silicone scaffolds were printed and cured using three different conditions relevant to potential future incorporation of temperature-sensitive labile biologics. Compressive strength and drug release were monitored for 14d in simulated vaginal fluid to assess long-term effects of fabrication conditions on mechanical integrity and release kinetics. Scaffolds were mechanically evaluated to determine compressive and tensile strength, and elastic modulus. Release profiles were fitted to previous kinetic models to differentiate potential release mechanisms. The Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models best described the release, indicating similarity to release from insoluble or polymeric matrices. This study shows the feasibility of 3D printed silicone scaffolds to provide sustained metronidazole release over 14d, with compressive strength and drug release kinetics tuned by the fabrication parameters.

Triamcinolone acetonide release modelling from novel bilayer mucoadhesive films: an in vitro study.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a painful disorder that commonly appears as ulcers on the oral mucosa, lasting ∼two weeks (minor) to months (major and herpetiform). Current treatment often necessitates the use of topical steroids in the form of pastes, mouthwashes, or gels, but these forms are often ineffective due to inadequate drug contact time with the ulcers. In this study, the performance of novel bilayer mucoadhesive buccal films loaded with triamcinolone acetonide (TA) has been evaluated for targeted drug delivery. METHODS: Experimental mucoadhesive films of hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), and polyvinyl pyrrolidone (PVP) were prepared by the solvent casting method, and ethyl cellulose (EC) was applied as the backing layer. The films were characterized for their physical properties, including swelling index (SI), folding endurance, adhesion force with porcine buccal mucosa, residence time and in-vitro drug release. RESULTS: The data showed that the films were flexible with folding endurance> 300 times. With porcine buccal mucosa i) suitable adhesion forces were obtained (between 2.72 and 4.03 N), ii) residence times of> 24 h, and iii) surface pH between 6.8 and 7.1 indicating they would be non-irritant. All films released 100% TA over 6 h, but with varying profiles. The release of TA (over 6 h) from PVP-free films followed Fickian diffusion kinetics (diffusion-controlled release of drug), whereas the mechanism of release from PVP-containing films was found to be a superposition of diffusion-controlled and erosion-controlled release (anomalous). SIGNIFICANCE: The developed films hold great promise for potentially treating RAS and other oral conditions.