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; Tzetzis, Dimitrios; Andreadis, Dimitrios; Boetker, Johan; Rantanen, Jukka; Fatouros, Dimitrios G.

doi:10.1016/j.ejpb.2019.09.018

Cited by 100 publications

(58 citation statements)

References 79 publications

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“…The experiments revealed greater F max and W ad values for all specimens, compared to PBS. Regarding the content of microparticles in the films, alterations in the bioadhesion parameters were further recorded, due to the simultaneous incorporation of the bioadhesive chitosan [30,31]. Up to a certain amount of CCP, a significant enhancement in the bioadhesive performance of the specimens was evidenced (P < 0.05), as the formulation comprising 20% w/w CCP exhibited F max and W ad values of approximately 6.4 and 8.8 N × mm, respectively.…”

Section: Bioadhesion Studiesmentioning

confidence: 96%

Development of Bio-Active Patches Based on Pectin for the Treatment of Ulcers and Wounds Using 3D-Bioprinting Technology

et al. 2020

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Biodegradable 3D-printable inks based on pectin have been developed as a system for direct and indirect wound-dressing applications, suitable for 3D printing technologies. The 3D-printable inks formed free-standing transparent films upon drying, with the latter exhibiting fast disintegration upon contact with aqueous media. The antimicrobial and wound-healing activities of the inks have been successfully enhanced by the addition of particles, comprised of chitosan and cyclodextrin inclusion complexes with propolis extract. Response Surface Methodology (RSM) was applied for the optimization of the inks (extrusion-printing pressure, shrinkage minimization over-drying, increased water uptake and minimization of the disintegration of the dry patches upon contact with aqueous media). Particles comprised of chitosan and cyclodextrin/propolis extract inclusion complexes (CCP), bearing antimicrobial properties, were optimized and integrated with the produced inks. The bioprinted patches were assessed for their cytocompatibility, antimicrobial activity and in vitro wound-healing properties. These studies were complemented with ex vivo skin adhesion measurements, a relative surface hydrophobicity and opacity measurement, mechanical properties, visualization, and spectroscopic techniques. The in vitro wound-healing studies revealed that the 3D-bioprinted patches enhanced the in vitro wound-healing process, while the incorporation of CCP further enhanced wound-healing, as well as the antimicrobial activity of the patches.

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Section: Bioadhesion Studiesmentioning

confidence: 96%

Development of Bio-Active Patches Based on Pectin for the Treatment of Ulcers and Wounds Using 3D-Bioprinting Technology

et al. 2020

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“…Amongst the aforementioned platforms, only FDM allows the use of hot-melt extrusion (HME) based filaments which are known for their capabilities of solubility enhancement, specifically for BCS class II drugs [ 16 , 17 ], which makes it a preferred platform for drugs with poor water solubility over the other techniques. Moreover, FDM is known to have the most versatility in terms of designing 3-D structures [ 18 , 19 , 20 ] and the available pharmaceutical polymers compatible with the process [ 20 , 21 , 22 , 23 ]. It has been recognized that FDM has the most immediate potential for unit dose fabrication as it uses polymeric filaments which could be customized or tuned to the specific needs of the printed products.…”

Section: Introductionmentioning

confidence: 99%

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

et al. 2020

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This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

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“…Since this work, there have been significant advancements in 3D printing pharmaceuticals using inkjet printing as well as other printing technologies. The technologies used for drug product development are powder-based printing (powder bed and powder jetting) [13][14][15][16], extrusion (solid or semi-solid) based printing (fused deposition modelling (FDM), pressure-assisted microsyringes (PAM)) [17][18][19][20][21][22][23][24][25][26], stereolithographic (SLA) printing [27][28][29], selective laser sintering (SLS) printing [30][31][32], inkjet printing [33][34][35], digital light processing (DLP) [36,37], etc. Among all these printing processes, extrusion-based printing (FDM, PAM) has shown a growing interest among researchers due to the advantage of low cost, ability to fabricate hollow objects, ability to print using a range of polymers with or without drug, ability to tune drug release by tuning the geometry and polymer, and ability to print at room temperature (using PAM), etc.…”

Section: Introductionmentioning

confidence: 99%

Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective

et al. 2020

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Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of 'one size fits for all'. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing. Among all 3D printing processes, extrusion-based (both fused deposition modeling (FDM) and pressure-assisted microsyringe (PAM)) 3D printing is well researched for pharmaceutical manufacturing. It is important to understand which polymers are suitable for extrusion-based 3D printing of pharmaceuticals and how their properties, as well as the behavior of polymer–active pharmaceutical ingredient (API) combinations, impact the printing process. Especially, understanding the rheology of the polymer and API–polymer mixtures is necessary for successful 3D printing of dosage forms or printed structures. This review has summarized a holistic materials–process perspective for polymers on extrusion-based 3D printing. The main focus herein will be both FDM and PAM 3D printing processes. It elaborates the discussion on the comparison of 3D printing with the traditional direct compression process, the necessity of rheology, and the characterization techniques required for the printed structure, drug, and excipients. The current technological challenges, regulatory aspects, and the direction toward which the technology is moving, especially for personalized pharmaceuticals and multi-drug printing, are also briefly discussed.

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

Cited by 100 publications

References 79 publications

Development of Bio-Active Patches Based on Pectin for the Treatment of Ulcers and Wounds Using 3D-Bioprinting Technology

Development of Bio-Active Patches Based on Pectin for the Treatment of Ulcers and Wounds Using 3D-Bioprinting Technology

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective

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