In Vitro Evaluation of 2D-Printed Edible Films for the Buccal Delivery of Diclofenac Sodium

Printing technologies have recently emerged in the development of novel drug delivery systems toward personalized medicine, to improve the performance of formulations, existing bioavailability patterns, and patients’ compliance. In the context of two-dimensional printing, this article presents the development of buccal films that are designed to efficiently deliver a class II compound (diclofenac sodium), according to the Biopharmaceutics Classification System (BCS), to the oral cavity. The preparation of drug-loaded inks was carried out based on solubility studies and evaluation of rheological properties, combining ethanol and propylene glycol as optimal solvents. Deposition of the drug was achieved by increasing the number of printing layers onto edible substrates, to produce formulations with dose variance. Thermal analysis, X-ray diffraction, and infrared spectroscopy were used to characterize the developed films. Drug loading and water uptake studies complemented the initial assessment of the films, and preliminary in vitro studies were conducted to further evaluate their performance. The in vitro release profiles were recorded in simulated saliva, presenting the complete release of the incorporated active in a period of 10 min. The effect of multiple layers on the overall performance of films was completed with in vitro permeation studies, revealing the correlation between the number of printed layers and the apparent permeability coefficient

Development and Characterization of Inkjet Printed Edible Films for Buccal Delivery of B-Complex Vitamins

Buccal films containing two vitamins, i.e., thiamine hydrochloride (THCl) and nicotinic acid (NA), were fabricated via two-dimensional (2D) inkjet printing. For the preparation of buccal films, solubility studies and rheological evaluations were conducted in distilled water and propylene-glycol (PG) as main solvent and viscosity/surface tension modifier, respectively. The increased solubility in the solvents’ mixture indicated that manufacturing of several doses of the THCl and NA is achievable. Various doses were deposited onto sugar-sheet substrates, by increasing the number of printing passes. The physiochemical characterization (SEM, DSC, FTIR) revealed that inkjet printing does not affect the solid state of the matrix. Water uptake studies were conducted, to compare the different vitamin-loaded formulations. The in vitro release studies indicated the burst release of both vitamins within 10 min, a preferable feature for buccal administration. The in vitro permeation studies indicated that higher concentrations of the vitamins onto the sugar sheet improved the in vitro permeation performance of printed formulations

Effect of Glyceryl Monoolein Addition on the Foaming Properties and Stability of Whipped Oleogels

Medium Chain Triglyceride (MCT) oil was successfully combined with Glyceryl Monostearate (GMS) and Glyceryl Monoolein (GMO) to form oleogels that were subsequently whipped to form stable oleofoams. The co-crystallization of GMS and GMO at a ratio of 20:1, 20:2.5, and 20:5 within MCT oil was studied through Differential Scanning Calorimetry (DSC), X-ray Diffraction analysis (XRD), rheological analysis, Fluorescence Recovery after Photobleaching (FRAP), Fourier Transform Infrared Spectroscopy (FTIR), and polarized microscopy. The addition of 5% GMO resulted in the production of more stable oleogels in terms of crystal structure and higher peak melting point, rendering this formulation suitable for pharmaceutical applications that are intended to be used internally and those that require stability at temperatures close to 40 °C. All formulations were whipped to form oleofoams that were evaluated for their storage stability for prolonged period at different temperatures. The results show that oleofoams containing 5% MGO retained their foam characteristics even after 3 months of storage under different temperature conditions

Fabrication and Preliminary In Vitro Evaluation of 3D-Printed Alginate Films with Cannabidiol (CBD) and Cannabigerol (CBG) Nanoparticles for Potential Wound-Healing Applications

In this study, drug carrier nanoparticles comprised of Pluronic-F127 and cannabidiol (CBD) or cannabigerol (CBG) were developed, and their wound healing action was studied. They were further incorporated in 3D printed films based on sodium alginate. The prepared films were characterized morphologically and physicochemically and used to evaluate the drug release profiles of the nanoparticles. Additional studies on their water loss rate, water retention capacity, and 3D-printing shape fidelity were performed. Nanoparticles were characterized physicochemically and for their drug loading performance. They were further assessed for their cytotoxicity (MTT Assay) and wound healing action (Cell Scratch Assay). The in vitro wound-healing study showed that the nanoparticles successfully enhanced wound healing in the first 6 h of application, but in the following 6 h they had an adverse effect. MTT assay studies revealed that in the first 24 h, a concentration of 0.1 mg/mL nanoparticles resulted in satisfactory cell viability, whereas CBG nanoparticles were safe even at 48 h. However, in higher concentrations and after a threshold of 24 h, the cell viability was significantly decreased. The results also presented mono-disperse nano-sized particles with diameters smaller than 200 nm with excellent release profiles and enhanced thermal stability. Their entrapment efficiency and drug loading properties were higher than 97%. The release profiles of the active pharmaceutical ingredients from the films revealed a complete release within 24 h. The fabricated 3D-printed films hold promise for wound healing applications; however, more studies are needed to further elucidate their mechanism of action

Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.</p

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.</p