A floating 3D printed polypill formulation for the coadministration and sustained release of antihypertensive drugs.

Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API's). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release. The dosage forms (polypills) containing three anti-hypertensive API's (diltiazem (DIL), propranolol (PRP) and hydrochlorothiazide (HCTZ)) were created via Fused Deposition Modelling 3D printing. A multitude of the dosage forms were loaded into a capsule and the resulting formulation achieved prolonged retention times over a 12-hour period in vitro, by leveraging both the buoyancy of the dosage forms, and the "cheerios effect" that facilitates the aggregation and retention of the dosage forms via a combination of surface tension and shape of the objects. Physicochemical characterization methods and imaging techniques were employed to investigate the properties and the internal and external structure of the dosage forms. Furthermore, an ex vivo porcine stomach model revealed substantial aggregation, adhesion and retention of the 3D printed dosage forms in porcine stomach. In vitro dissolution testing demonstrated almost complete first-order release of PRP and DIL (93.52 % and 99.9 %, respectively) and partial release of HCTZ (65.22 %) in the 12 h timeframe. Finally, a convolution-based single-stage approach was employed in order to predict the pharmacokinetic (PK) parameters of the API's of the formulation and the resemblance of their PK behavior with previously reported data.

In situ triggered, floating delivery systems of capsaicin for prolonged gastroprotection.

Capsaicin (CAP) has been implicated as a gastroprotective agent in the treatment of peptic ulcers. However, its oral administration is hampered by its poor aqueous solubility and caustic effect at high administered doses. To address these limitations, we describe the development of gastric floating, sustained release electrospun films loaded with CAP. The nanofiber films were formulated using the polymers Eudragit RL/RS and sodium bicarbonate (SB) as the effervescent agent. The films were tested for their physicochemical properties, and film buoyancy and in vitro release of CAP were assessed in simulated gastric fluid. The cytocompatibility and anti-inflammatory properties of the films were evaluated in lipopolysaccharide (LPS)-stimulated Caco-2 cells. The amorphous films showed improved wettability, a short floating lag time (<1 s) and a total floating time of over 24 h accompanied by sustained CAP release for up to 24 h. CAP-loaded films demonstrated biocompatibility with Caco-2 cells and potential cytoprotective effects by attenuating inflammatory cytokine and reactive oxygen species (ROS) production in LPS-stimulated Caco-2 cells. The gastric floating electrospun films could serve as a platform for sustained and stomach-specific drug delivery applications.

Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Small patients, big challenges: navigating pediatric drug manipulations to prevent medication errors - a comprehensive review.

INTRODUCTION: Medication errors during drug manipulations in pediatric care pose significant challenges to patient safety and optimal medication management. Epidemiological studies have revealed a high prevalenceof medication errors throughout the medication process. Due to the lack of age-appropriate dosage forms, medication manipulation is common in pediatric drug administration. The consequences of these manipulations on drug efficacy and safety could be devastating, highlighting the need for evidence-based guidelines and standardized compounding practices. AREAS COVERED: This review focuses on examining medication errors in pediatric care and delving into the manipulation of medicinal products. EXPERT OPINION: The observed prevalence of medication errors and manipulations underscores the importance of addressing these issues to enhance patient safety and improve medication outcomes in pediatric care. Overall, the development of age-appropriate formulations and the dissemination of comprehensive clinical guidelines are essential steps toward improving medication safety and minimizing manipulations in pediatric healthcare settings.

Modular Titratable Polypills for Personalized Medicine and Simplification of Complex Medication Regimens.

Simplification of complex medication regimens in polypharmacy positively contributes to treatment adherence and cost-effective improved health outcomes. Even though fixed dose combination (FDC) drug products are the only currently available single dose poly-pill regimens, the lack of flexibility in dose adjustment of a single drug in the combination limits their efficacy. To fill the existing gap in drug dose personalization and simplification of complex medication regimens commonly encountered in the treatment of cardiovascular disease, tuberculosis, and tapering of corticosteroid therapy, a modular titratable polypill approach that simultaneously addresses both aspects is proposed. The polypill consists of modular units that contain different drugs at incremental or decremental doses to be assembled in a single titratable polypill at the required dose for each drug through a stacking or interlocking process. The variable dose (VD) modular tablets are subjected to quality control tests and found to comply to pharmacopeia's acceptance criteria and requirements specified in the respective drug monographs. A cost-effectiveness analysis is conducted supporting the VD strategy as cost-effective compared to the FDC strategy and more effective and less expensive than standard of care. The VD approach stands to enable pill burden reduction, ease of administration, enhancement of treatment adherence, and potential cost-saving benefits.

Pediatric and Geriatric-Friendly Buccal Foams: Enhancing Omeprazole Delivery for Patients Encountering Swallowing Difficulties.

Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.

In vitro and in silico computational methods for assessing vaginal permeability.

OBJECTIVE: Vaginal administration is an important alternative to the oral route for both topical and systemic use. Therefore, the development of reliable in silico methods for the study of drugs permeability is becoming popular in order to avoid time-consuming and costly experiments. METHODS: In the current study, Franz cells and appropriate HPLC or ESI-Q/MS analytical methods were used to experimentally measure the apparent permeability coefficient (Papp) of 108 compounds (drugs and non-drugs). Papp values were then correlate with 75 molecular descriptors (physicochemical, structural, and pharmacokinetic) by developing two Quantitative Structure Permeability Relationship (QSPR) models, a Partial Least Square (PLS) and a Support Vector Machine (SVM). Both were validated by internal, external and cross-validation. RESULTS: Based on the calculated statistical parameters (PLS model A: R2 = 0.673 and Q2 = 0.594, PLS model B: R2 = 0.902 and Q2 = 0.631, SVM: R2 = 0.708 and Q2 = 0.758). SVM presents higher predictability while PLS adequately interprets the theory of permeability. CONCLUSIONS: The most important parameters for vaginal permeability were found to be the relative PSA, logP, logD, water solubility and fraction unbound (FU). Respectively, the combination of both models could be a useful tool for understanding and predicting the vaginal permeability of drug candidates.

Exploring the Role of Self-Nanoemulsifying Systems in Drug Delivery: Challenges, Issues, Applications and Recent Advances.

Nanotechnology has attracted researchers around the globe owing to the small size and targeting properties of the drug delivery vectors. The interest in self-nanoemulsifying drug delivery systems (SNEDDS) has shown an exponential increase from the formulator's point of view. SNEDDS have shown wide applicability in terms of controlled and targeted delivery of various types of drugs. They chemically consist of oil, surfactants and co-surfactants that decrease the emulsion particle size to the range of <100 nm. However, stability issues such as drug precipitation during storage, incompatibility of ingredients in shell, decrease their application for the long run and these issues have been highlighted in this paper. The current review throws limelight on the biological aspects and process parameters. In addition, the process of absorption from GI is also discussed in detail. SNEDDS have been utilized as a treatment option for various diseases like cancer, diabetes, and ocular and pulmonary diseases. Along with this, the authors highlight the advances involving in vivo and in vitro lipolysis studies on SNEDDS, also highlighting recent innovations in this field, such as novel combinations of drug-free solid SNEDDS + solid dispersions, lipid-modified chitosan containing mucoadhesive SNEDDS, pHsensitive SNEDDS and several others.

A simple and green liquid chromatography method for the determination of ibuprofen in milk-containing simulated gastrointestinal media for monitoring the dissolution studies of three-dimensional-printed formulations.

A fast and green ultra-high-performance liquid chromatographic method was developed for the determination of ibuprofen in milk-containing simulated gastrointestinal media to monitor the dissolution of three-dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01 µg/ml and the lower limit of quantitation was established as 2 µg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.

Quality control evaluation of paediatric chocolate-based dosage forms: 3D printing vs mold-casting method.

Pharmaceutical compounding is a core activity in the preparation of patient-specific dosage forms. In the current study we aimed to investigate whether 3D printing could be employed for the preparation of pediatric-friendly personalized dosage forms that fulfil the acceptance criteria specified in the pharmacopoeias for conventional dosage forms. We then compared the 3D printed dosage forms with the same formulations prepared with mold-casting, a method frequently applied during pharmaceutical compounding. The molded dosage forms failed to pass most of the quality control tests, including the mass uniformity and content uniformity tests, as well as dose accuracy, contrary to the 3D printed, which not only passed all tests but also enabled precision overdose adjustment. Hence, 3D printing of chocolate-based dosage forms may effectively serve as an acceptable alternative method to mold casting in compounding patient-specific medication at the point-of-care.

Development and Validation of an HPLC-UV Method for the Dissolution Studies of 3D-Printed Paracetamol Formulations in Milk-Containing Simulated Gastrointestinal Media.

Herein, a simple and rapid HPLC method for the determination of paracetamol milk-containing biorelevant media is proposed. The separation of the analyte from the milk-containing biorelevant media was accomplished isocratically using a mobile phase containing 25 mM phosphate buffer (pH = 3.0) and methanol, 80:20, v/v at a flow rate of 1 mL min-1. Following a protein precipitation-based sample clean-up, a thorough investigation of the effect of the precipitation reagent (methanol, acetonitrile, 10% v/v trifluoroacetic acid solution) on the analyte recovery was performed. The matrix effect was assessed in each biorelevant medium by comparing the slopes of the calibration curves of aqueous and matrix-matched calibration curves. The method was comprehensively validated using the accuracy profiles. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between -4.5 and +3.9% for all analytes, while the RSD values for repeatability and intermediate precision were less than 2.7% and 3.0%, respectively. The achieved limit of detection (LOD) was 0.02 µg mL-1 and the lower limits of quantitation (LLOQ) were established as 10 µg mL-1, which corresponded to 2% of the highest expected concentration of paracetamol. The proposed scheme was utilized for the determination of paracetamol in dissolution studies of its 3D-printed formulation in milk-containing biorelevant media.

Development of oil-based gels as versatile drug delivery systems for pediatric applications.

Administering medicines to 0- to 5-year-old children in a resource-limited environment requires dosage forms that circumvent swallowing solids, avoid on-field reconstitution, and are thermostable, cheap, versatile, and taste masking. We present a strategy that stands to solve this multifaceted problem. As many drugs lack adequate water solubility, our formulations used oils, whose textures could be modified with gelling agents to form "oleogels." In a clinical study, we showed that the oleogels can be formulated to be as fluid as thickened beverages and as stiff as yogurt puddings. In swine, oleogels could deliver four drugs ranging three orders of magnitude in their water solubilities and two orders of magnitude in their partition coefficients. Oleogels could be stabilized at 40°C for prolonged durations and used without redispersion. Last, we developed a macrofluidic system enabling fixed and metered dosing. We anticipate that this platform could be adopted for pediatric dosing, palliative care, and gastrointestinal disease applications.

Electrospun Nanofiber Films Suppress Inflammation In Vitro and Eradicate Endodontic Bacterial Infection in an E. faecalis-Infected Ex Vivo Human Tooth Culture Model.

Treatment failure of endodontic infections and their concurrent inflammations is commonly associated with microbial persistence and reinfection, also stemming from the anatomical restrictions of the root canal system. Aiming to address the shortcomings of current treatment options, a fast-disintegrating nanofibrous film was developed for the intracanal coadministration of an antimicrobial (ZnO nanoparticles) and an anti-inflammatory (ketoprofen) agent. The electrospun films were fabricated based on polymers that dissolve rapidly to constitute the actives readily available at the site of action, aiming to eliminate both microbial infection and inflammation. The anti-inflammatory potency of the nanofiber films was assessed in an in vitro model of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after confirming their biocompatibility in the same cell line. The nanofiber films were found effective against Enterococcus faecalis, one of the most prominent pathogens inside the root canal space, both in vitro and ex vivo using a human tooth model experimentally infected with E. faecalis. The physical properties and antibacterial and anti-inflammatory potency of the proposed electrospun nanofiber films constitute a promising therapeutic module in the endodontic therapy of nonvital infected teeth. All manuscripts must be accompanied by an abstract. The abstract should briefly state the problem or purpose of the research, indicate the theoretical or experimental plan used, summarize the principal findings, and point out major conclusions.

Cereal-Based 3D Printed Dosage Forms for Drug Administration During Breakfast in Pediatric Patients within a Hospital Setting.

In an effort to combine a child-friendly dosage form for medication administration in hospitalized pediatric patients and a user-friendly automated process for its preparation by health-care providers, the current study proposes a method for drug administration with breakfast using semi-solid extrusion 3D printing. Cereal was used as the platform carrier of the hydrophobic ibuprofen and the hydrophilic paracetamol to develop the drug loaded cereal ink. Rheological analysis was performed to identify the cereal ink with optimum viscosity for extrusion printing. Drug distribution and crystallinity within the printed cereal were assessed with confocal Raman microscopy and thermal and X-ray diffraction analysis, respectively, indicating molecular dispersion of both drugs within the cereal. High cereal porosity was associated with a higher milk absorption capacity and a decrease in their flexural force upon immersion in milk. Dissolution studies were performed in biorelevant media under fasted and fed state conditions and in the presence of full-fat and low-fat milk showing dissolution enhancement of the poorly soluble ibuprofen in the presence of the higher fat content milk. Concealing drug administration under the auspice of this essential daily eating habit is expected to facilitate overcoming adherence barriers to medication intake by pediatric patients within a hospital setting.

Development and validation of HPLC-DAD and LC-(ESI)/MS methods for the determination of sulfasalazine, mesalazine and hydrocortisone 21-acetate in tablets and rectal suppositories: In vitro and ex vivo permeability studies.

Controlled-release tablets and rectal suppositories of sulfasalazine (SLF) and hydrocortisone 21-acetate (HA) were prepared as recommended dosage forms for the treatment of acute episodes of ulcerative colitis, in patients who do not respond to monotherapy. A High-Performance Liquid Chromatography (HPLC) Diode-array method with a gradient elution mobile phase was developed to evaluate the production quality of both formulations (assay and dissolution profiles in gastric and intestinal fluids). Method's validation was carried out providing good linearity (r ≥ 0.9995), precision (RSD < 1.53%), recovery (96.9% - 103.7%) and limits of detection (LODSLF = 12 ng/mL, LODHA = 15 ng/mL). Experimental design and Plackett-Burman methodology was constructed to study the robustness of the analysis. In all composite substrates, a freezing lipid precipitation approach was used as purification step. The method was optimized by applying Central Composite design mode. The in-vitro/ex-vivo permeability studies of both formulations were evaluated by a Liquid Chromatography-Electron Spray Ionization Mass Spectrometry (LC-ESI/MS) +/- mode. The analysis of sulfamethazine (internal standard, SLM, m/z 279), HA (m/z 449, [M + HCOO]-), SLF (m/z 399) and its active metabolite mesalazine (MSL, m/z 154) was performed using a C18 column and gradient elution. The validation of the method met the requirements of the International Council for Harmonization (ICH) (r ≥ 0.9997, RSD ≤ 4.62%, Recovery > 95%, LODSLF = 1.28 ng/mL, LODHA = 1.07 ng/mL, LODMSL = 3.16 ng/mL). Based on the results, important conclusions were drawn concerning the role of excipients and SLF metabolism.

Silk sericin/PLGA electrospun scaffolds with anti-inflammatory drug-eluting properties for periodontal tissue engineering.

Periodontal disease is associated with chronic inflammation and destruction of the soft and hard tissues in the periodontium. Scaffolds that would enable cell attachment and proliferation while at the same time providing a local sustained anti-inflammatory action would be beneficial in restoring or reversing disease progression. In the current study, silk sericin, a natural protein derived from the silkworm cocoons, was electrospun with poly lactide-co-glycolic acid (PLGA) and ketoprofen, and the composite scaffolds were assessed for their physicochemical and mechanical properties, as well as their biocompatibility and in vitro anti-inflammatory action. The composite scaffolds showed an increase in their hydrophilicity and an exceptional reinforcement of their mechanical properties, compared to plain PLGA scaffolds, sustaining drug release for up to 15 days. Human gingival fibroblasts showed a favorable attachment and proliferation on the composite scaffolds as visualized with scanning electron and confocal microscopy. A significant downregulation of the pro-inflammatory markers MMP-9 and MMP-3 and an upregulation of the anti-inflammatory gene IL-10 was achieved for lipopolysaccharide-stimulated RAW 264.7 macrophages after cultivation on the composite scaffolds. The current study demonstrated that silk sericin-PLGA composite scaffolds have the potential to simultaneously accommodate cell attachment and proliferation and achieve a sustained anti-inflammatory action in the treatment of periodontal diseases.

Analytical quality-by-design optimization of UHPLC method for the analysis of octreotide release from a peptide-based hydrogel in-vitro.

In this article, a UHPLC-PDA method has been developed using the quality-by-design (QbD) principles for the determination of the therapeutic peptide - octreotide - in its in vitro released samples. Due to the complexity of the peptide-based hydrogel matrix a reliable separation of the analyte from the matrix has to be performed. Risk assessment and multivariate analysis were employed for the method evaluation. Following method scouting towards the selection of appropriate and rapid UHPLC operative mode, quality risk assessment tools were applied to set the critical method parameters (CMPs) to be considered in screening phase. The effects of CMPs on critical method attributes (CMAs) were assessed further by means of a screening design. A response surface methodology was utilized to model CMAs as a function of the selected CMPs and the optimum separation conditions were additionally evaluated using desirability function. The method operable design region was complimented by establishment of a robust zone using Monte Carlo simulation and capability analysis. The method was validated in the range of 1 - 20 µg /mL using the accuracy profiles as a graphical decision-making tool. The ß-expectation tolerance intervals was within the pre-set acceptance criteria of ± 10% meaning that 95% of future results will be included in the defined bias limits. The relative bias was varied between ─ 0.8% and 1.4% and the RSD values for repeatability and intermediate precision were below to 2.8% in all cases. The achieved limit of detection (LOD) and the lower limit of quantification (LLOQ) were adequate for the specific purpose and found to be 0.3 and 1 µg /mL, respectively. The developed method was successfully applied to the analysis of octreotide in in-vitro drug release samples obtained from peptide-based hydrogels.

NGIWY-Amide: A Bioinspired Ultrashort Self-Assembled Peptide Gelator for Local Drug Delivery Applications.

Fibrillar structures derived from plant or animal origin have long been a source of inspiration for the design of new biomaterials. The Asn-Gly-Ile-Trp-Tyr-NH2 (NGIWY-amide) pentapeptide, isolated from the sea cucumber Apostichopus japonicus, which spontaneously self-assembles in water to form hydrogel, pertains to this category. In this study, we evaluated this ultra-short cosmetic bioinspired peptide as vector for local drug delivery applications. Combining nuclear magnetic resonance, circular dichroism, infrared spectroscopy, X-ray diffraction, and rheological studies, the synthesized pentapeptide formed a stiff hydrogel with a high ß-sheet content. Molecular dynamic simulations aligned well with scanning electron and atomic-force microscopy studies, revealing a highly filamentous structure with the fibers adopting a helical-twisted morphology. Model dye localization within the supramolecular hydrogel provided insights on the preferential distribution of hydrophobic and hydrophilic compounds in the hydrogel network. That was further depicted in the diffusion kinetics of drugs differing in their aqueous solubility and molecular weight, namely, doxorubicin hydrochloride, curcumin, and octreotide acetate, highlighting its versatility as a delivery vector of both hydrophobic and hydrophilic compounds of different molecular weight. Along with the observed cytocompatibility of the hydrogel, the NGIWY-amide pentapeptide may offer new approaches for cell growth, drug delivery, and 3D bioprinting tissue-engineering applications.

Semi-solid extrusion 3D printing of starch-based soft dosage forms for the treatment of paediatric latent tuberculosis infection.

OBJECTIVES: The development of age-appropriate dosage forms is essential for effective pharmacotherapy, especially when long-term drug treatment is required, as in the case of latent tuberculosis infection treatment with up to 9 months of daily isoniazid (ISO). Herein, we describe the fabrication of starch-based soft dosage forms of ISO using semi-solid extrusion (SSE) 3D printing. METHODS: Corn starch was used for ink preparation using ISO as model drug. The inks were characterized physicochemically and their viscoelastic properties were assessed with rheological analysis. The morphology of the printed dosage forms was visualized with scanning electron microscopy and their textural properties were evaluated using texture analysis. Dose accuracy was verified before in-vitro swelling and dissolution studies in simulated gastric fluid (SGF). KEY FINDINGS: Starch inks were printed with good resolution and high drug dose accuracy. The printed dosage forms had a soft texture to ease administration in paediatric patients and a highly porous microstructure facilitating water penetration and ISO diffusion in SGF, resulting in almost total drug release within 45 min. CONCLUSIONS: The ease of preparation and fabrication combined with the cost-effectiveness of the starting materials constitutes SSE 3D printing of starch-based soft dosage forms a viable approach for paediatric-friendly formulations in low-resource settings.

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment.

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.