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

Abstract

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

“…However, the 5-and 9-printed films presented lower vitamin dosing than expected, when compared to the 1-printed film. The disproportionate increase in dosing of inkjet-printed formulations, in relation to the number of printing passes, has been previously reported and associated with the shear forces that develop during the feeding process of the printer [49,50]. The conveyance of the edible sheets to the printing zone occurs upon traction of the substrate by the drive rollers of the device.…”

“…Two broad endotherm peaks were detected in the temperature range of 70-150 • C and 190-250 • C for the plain sugar sheet and the formulations. These peaks are attributed to the evaporation of water and to the endothermic patterns of maltodextrin and sugar monosaccharides [50]. In the FTIR spectrum of THCl, characteristic peaks at 1650 cm −1 and 1600 cm −1 corresponded to the stretching bonds of C = N and aromatic C = C respectively [53] and peaks at 1347 cm −1 and 1438 cm −1 corresponded to the stretching modes of CH group of the pyrimidine ring [54].…”

“…These vibrations were associated with the presence of maltodextrin, which is incorporated in the composition of the sugar sheet [55]. The absence or lower transmittance of the characteristic vibrations in the developed formulations including the ink solution, suggests that the vitamins content was either below the detection limit of the device or the vitamins were molecularly dissolved in the substrate matrix [50,56].…”

Oromucosal films: from patient centricity to production by printing techniques

“…In this study, it was also shown that the bigger the drop volume the higher is the crystalline proportion because small drops dry faster and the drug substance has less time for crystallization. The more printing passes the higher was the amorphous ratio due to the increasing amount of propylene glycol and higher solvation of the drug [103,106]. With increased drug content, the recrystallization rate can increase and drug crystals can be formed on the top of the oromucosal films [95].…”

A Pediatrics Utilization Study in The Netherlands to Identify Active Pharmaceutical Ingredients Suitable for Inkjet Printing on Orodispersible Films

“…From the final selection of APIs, diclofenac [36], indomethacin [32,37], montelukast [38] and prednisolone (frequently dispensed instead of prednisone, as listed in Table 3) [39] have been already successfully printed using the inkjet technique on ODFs or transparency sheets. In the case of montelukast and prednisolone, the therapeutic dose was achieved, however, in the case of diclofenac and indomethacin, the printed dose remained too low.…”