Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation

Georgios K. Eleftheriadis; Christos Ritzoulis; Nikolaos Bouropoulos; Dimitrios Tzetzis; Dimitrios A. Andreadis; Johan Boetker; Jukka Rantanen; Dimitrios G. Fatouros

doi:10.1016/j.ejpb.2019.09.018

Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation

Georgios K. Eleftheriadis, Christos Ritzoulis, Nikolaos Bouropoulos, Dimitrios Tzetzis, Dimitrios A. Andreadis, Johan Boetker, Jukka Rantanen, Dimitrios G. Fatouros^*

^*Corresponding author for this work

30 Citations (Scopus)

Abstract

Oromucosal delivery of active pharmaceutical ingredients provides an attractive alternative route of administration, due to avoidance of the first pass effect and improved patient compliance. In the current work, fused deposition modelling (FDM) 3D printing was investigated as an additive manufacturing approach for poly(vinyl alcohol)-based mucoadhesive films, enabling unidirectional drug release. For this purpose, chitosan was incorporated as a permeation and mucoadhesion enhancer whereas ethylcellulose and commercial wafer sheets were evaluated as backing layers. The formulated films were initially assessed for structural integrity and dose uniformity. Solid-state characterization of the films, including thermal methods (DSC, TGA), diffraction (XRPD) and Raman spectroscopy, was implemented to characterize the physicochemical properties of the produced polymeric filaments and buccal films. The mechanical properties of the products were investigated by instrumented indentation and tensile tests. Evaluation of buccal films was assessed in vitro, to study the effect of backing-layer type on hydration capacity of the films, diffusion of the drug throughout the restricting layer and release profiles in simulated saliva. The ex vivo performance of the manufactured products, associated with the presence of chitosan, was investigated by textural analysis for mucoadhesion properties, whereas permeation studies and histological studies were performed across porcine buccal epithelium. The results demonstrated that FDM printing is a timesaving and versatile approach in the context of manufacturing multi-layered mucoadhesive buccal films, providing unidirectional release properties.

Original language	English
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	144
Pages (from-to)	180-192
Number of pages	13
ISSN	0939-6411
DOIs	https://doi.org/10.1016/j.ejpb.2019.09.018
Publication status	Published - Nov 2019

Keywords

3D printing
Backing layer
Buccal
Chitosan
Diclofenac
FDM
Mucoadhesion
Unidirectional

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10.1016/j.ejpb.2019.09.018

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Eleftheriadis, G. K., Ritzoulis, C., Bouropoulos, N., Tzetzis, D., Andreadis, D. A., Boetker, J., Rantanen, J., & Fatouros, D. G. (2019). Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation. European Journal of Pharmaceutics and Biopharmaceutics, 144, 180-192. https://doi.org/10.1016/j.ejpb.2019.09.018

Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation. / Eleftheriadis, Georgios K.; Ritzoulis, Christos; Bouropoulos, Nikolaos et al.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 144, 11.2019, p. 180-192.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "Oromucosal delivery of active pharmaceutical ingredients provides an attractive alternative route of administration, due to avoidance of the first pass effect and improved patient compliance. In the current work, fused deposition modelling (FDM) 3D printing was investigated as an additive manufacturing approach for poly(vinyl alcohol)-based mucoadhesive films, enabling unidirectional drug release. For this purpose, chitosan was incorporated as a permeation and mucoadhesion enhancer whereas ethylcellulose and commercial wafer sheets were evaluated as backing layers. The formulated films were initially assessed for structural integrity and dose uniformity. Solid-state characterization of the films, including thermal methods (DSC, TGA), diffraction (XRPD) and Raman spectroscopy, was implemented to characterize the physicochemical properties of the produced polymeric filaments and buccal films. The mechanical properties of the products were investigated by instrumented indentation and tensile tests. Evaluation of buccal films was assessed in vitro, to study the effect of backing-layer type on hydration capacity of the films, diffusion of the drug throughout the restricting layer and release profiles in simulated saliva. The ex vivo performance of the manufactured products, associated with the presence of chitosan, was investigated by textural analysis for mucoadhesion properties, whereas permeation studies and histological studies were performed across porcine buccal epithelium. The results demonstrated that FDM printing is a timesaving and versatile approach in the context of manufacturing multi-layered mucoadhesive buccal films, providing unidirectional release properties.",

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AU - Bouropoulos, Nikolaos

AU - Tzetzis, Dimitrios

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Unidirectional drug release from 3D printed mucoadhesive buccal films using FDM technology: In vitro and ex vivo evaluation

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Keywords

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