Additive Manufacturing Approaches to Produce Drug Delivery Systems Volume II

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 12193

Special Issue Editors

Centre for Rapid and Sustainable Product Development, Polytechnic Institute of Leiria, 2430-028 Leiria, Portugal
Interests: additive manufacturing; antimicrobial materials; biomaterials; chromatography; drug delivery systems; gene therapy; tissue engineering
Special Issues, Collections and Topics in MDPI journals
Centre for Rapid and Sustainable Product Development, Polytechnic of Leiria, 2430-028 Marinha Grande, Portugal
Interests: additive manufacturing; biomimetics and bioinspiration; computer-aided engineering; computer-aided manufacturing; multi-material 3D/4D structures; industrial/biomedical applications; tissue engineering; mould design and polymer injection moulding; circular economy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, additive manufacturing approaches have provided innovative and cutting-edge technologies that have significantly improved different fields. One of the applications of these methodologies is the production of enhanced drug delivery systems. In this regard, using these technologies enables the full manipulation of several drug delivery production parameters that are not able to be changed/combined when conventional approaches are used. Among these parameters are the porosity, layer and piece dimensions (from nanometres to the desirable), interconnectivity and mono- or multi-material production. Currently, the structures produced through additive manufacturing include scaffolds used on hard tissue regeneration, wound dressings made by fibres that can perfectly mimic the soft tissue and nanometric structures that can be used for transdermal medication. All these kinds of structures could be filled with drugs and biochemical markers leading to a quick and successful therapeutic process.

The potential topics for this Special Issue include, but are not limited to, the following:

  • Medicines (oral, rectal and vaginal);
  • Intravenous and transdermal approaches;
  • Scaffolds and wound dressings;
  • Additive manufacturing technologies for drug delivery systems;
  • Drug delivery mathematical models.

Dr. Joana Valente
Prof. Dr. Nuno Alves
Guest Editors

Manuscript Submission Information

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Keywords

  • additive manufacturing
  • drug delivery systems
  • scaffolds
  • wound dressings
  • intravenous and transdermal approaches
  • biomaterials
  • drug delivery mathematical models

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Published Papers (7 papers)

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Research

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17 pages, 3714 KiB  
Article
Study and Characterization of Polyvinyl Alcohol-Based Formulations for 3D Printlets Obtained via Fused Deposition Modeling
Pharmaceutics 2023, 15(7), 1867; https://doi.org/10.3390/pharmaceutics15071867 - 02 Jul 2023
Cited by 2 | Viewed by 1072
Abstract
Three-dimensional (3D) printing has emerged as a new promising technique for the production of personalized dosage forms and medical devices. Polyvinyl alcohol is prominently used as a source material to produce 3D-printed medicines via fused deposition modeling (FDM)—a technology that combines hot melt [...] Read more.
Three-dimensional (3D) printing has emerged as a new promising technique for the production of personalized dosage forms and medical devices. Polyvinyl alcohol is prominently used as a source material to produce 3D-printed medicines via fused deposition modeling (FDM)—a technology that combines hot melt extrusion and 3D printing. A preliminary screening of three grades of PVA indicated that partially hydrolyzed PVA with a molecular weight (MW) of 31,000–50,000 and plasticized with sorbitol was most suitable for 3D printing. Paracetamol was used as a model drug. The materials and the produced filaments were characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The complex viscosity (η*) of the polymer melts was determined as a function of the angular frequency (ω) at the printing temperature to assess their printability. Three-dimensional printlets with a 40% infill exhibited an immediate release of the API, while tablets with a higher infill were prone to a prolonged release regardless of the filament drug loading. A factorial design was used to give more insight into the influence of the drug-loading of the filaments and the tablet infill as independent variables on the production of 3D printlets. The Pareto chart confirmed that the infill had a statistically significant effect on the dissolution rate after 45 min, which was chosen as the response variable. Full article
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14 pages, 3567 KiB  
Article
A Computational Model for the Release of Bioactive Molecules by the Hydrolytic Degradation of a Functionalized Polyester-Based Scaffold
Pharmaceutics 2023, 15(3), 815; https://doi.org/10.3390/pharmaceutics15030815 - 02 Mar 2023
Cited by 2 | Viewed by 945
Abstract
This work presents a computational model to study the degradation behavior of polyester-based three-dimensional (3D) functionalized scaffolds for bone regeneration. As a case study, we investigated the behavior of a 3D-printed scaffold presenting a functionalized surface with ICOS-Fc, a bioactive protein able to [...] Read more.
This work presents a computational model to study the degradation behavior of polyester-based three-dimensional (3D) functionalized scaffolds for bone regeneration. As a case study, we investigated the behavior of a 3D-printed scaffold presenting a functionalized surface with ICOS-Fc, a bioactive protein able to stimulate bone regeneration and healing, inhibiting osteoclast activity. The aim of the model was to optimize the scaffold design to control its degradation and thus the release of grafted protein over time and space. Two different scenarios were considered: (i) a scaffold without macroporosity presenting a functionalized external surface; and (ii) a scaffold presenting an internal functionalized macroporous architecture with open channels to locally deliver the degradation products. Full article
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19 pages, 4163 KiB  
Article
Assessment of 3D-Printed Polycaprolactone, Hydroxyapatite Nanoparticles and Diacrylate Poly(ethylene glycol) Scaffolds for Bone Regeneration
Pharmaceutics 2022, 14(12), 2643; https://doi.org/10.3390/pharmaceutics14122643 - 29 Nov 2022
Cited by 5 | Viewed by 1791
Abstract
Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D-printed scaffolds with ideal mechanical and biological properties remains an unattained challenge. In the present work, a new approach to produce synthetic bone grafts [...] Read more.
Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D-printed scaffolds with ideal mechanical and biological properties remains an unattained challenge. In the present work, a new approach to produce synthetic bone grafts that mimic complex bone structure is explored. For the first time, three scaffolds of various composition, namely polycaprolactone (PCL), PCL/hydroxyapatite nanoparticles (HANp) and PCL/HANp/diacrylate poly(ethylene glycol) (PEGDA), were manufactured by extrusion. Following the production and characterisation of the scaffolds, an in vitro evaluation was carried out using human dental pulp stem/stromal cells (hDPSCs). Through the findings, it was possible to conclude that, in all groups, the scaffolds were successfully produced presenting networks of interconnected channels, adequate porosity for migration and proliferation of osteoblasts (approximately 50%). Furthermore, according to the in vitro analysis, all groups were considered non-cytotoxic in contact with the cells. Nevertheless, the group with PEGDA revealed hydrophilic properties (15.15° ± 4.06) and adequate mechanical performance (10.41 MPa ± 0.934) and demonstrated significantly higher cell viability than the other groups analysed. The scaffolds with PEGDA suggested an increase in cell adhesion and proliferation, thus are more appropriate for bone regeneration. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes. Full article
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15 pages, 1788 KiB  
Article
3D-Powder-Bed-Printed Pharmaceutical Drug Product Tablets for Use in Clinical Studies
Pharmaceutics 2022, 14(11), 2320; https://doi.org/10.3390/pharmaceutics14112320 - 28 Oct 2022
Cited by 2 | Viewed by 2062
Abstract
Printing of phase 1 and 2a clinical trial formulations represents an interesting industrial application of powder bed printing. Formulations for clinical trials are challenging because they should enable flexible changes in the strength of the dosage form by varying the active pharmaceutical ingredient [...] Read more.
Printing of phase 1 and 2a clinical trial formulations represents an interesting industrial application of powder bed printing. Formulations for clinical trials are challenging because they should enable flexible changes in the strength of the dosage form by varying the active pharmaceutical ingredient (API) percentage and tablet mass. The aim of this study was to investigate how powder bed 3D printing can be used for development of flexible platforms for clinical trials, suitable for both hydrophilic and hydrophobic APIs, using only conventional tableting excipients. A series of pre-formulation and formulation studies were performed to develop two platform formulations for clinical trials using acetaminophen and diclofenac sodium as model compounds and lactose and starch as excipients. The results showed that the type of starch used as the formulation binder must be optimized based on the type of API. Moreover, powder blend flow and liquid penetration ability proved to be critical material attributes (CMAs) that need to be controlled, particularly at high drug loading. Optimization of these CMAs was performed by selecting the appropriate particle size of the API or by addition of silica. A critical process parameter that had to be controlled for production of tablets of good quality was the quantity of the printing ink. After optimization of both the formulation and process parameters, two platform formulations, that is, one for each API, were successfully developed. Within each platform, drug loading from 5 up to 50% w/w and tablet mass from 50 to 500 mg were achieved. All 3D-printed tablets could be produced at tensile strength above 0.2 MPa, and most tablets could enable immediate release (i.e., >80% w/w within 30 min). Full article
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12 pages, 2243 KiB  
Article
Arginine-Modified 3D-Printed Chromatographic Supports
Pharmaceutics 2022, 14(11), 2266; https://doi.org/10.3390/pharmaceutics14112266 - 23 Oct 2022
Cited by 1 | Viewed by 1440
Abstract
The increasing progression of biopharmaceutical-based therapies highlights the demand for efficient chromatographic methods that can be used to purify the desired biomolecules (e.g., nucleic acids, enzymes, or monoclonal antibodies) which are presently under consideration in clinical trials or approved by the Food and [...] Read more.
The increasing progression of biopharmaceutical-based therapies highlights the demand for efficient chromatographic methods that can be used to purify the desired biomolecules (e.g., nucleic acids, enzymes, or monoclonal antibodies) which are presently under consideration in clinical trials or approved by the Food and Drug Administration. These molecules present distinct chemical and structural properties, which are critical cues for the development and production of adequate chromatographic supports. Until now, it has not been possible to fully control the characteristics of the chromatographic matrices to assure the total reproducibility of their structure and packing. Meanwhile, three-dimensional printing (3DP) is in the early stage of its use in the production of chromatographic supports as a fast, very precise, and reproducible methodology. Although 3DP can provide excellent performance properties to the chromatographic structures, it cannot, per se, lead to high-quality pharmaceutical products. However, the association of affinity ligands, such as amino acids, which is possible in 3DP, could enable the attainment of high-purity yields of the desired molecules. Beyond the amino acids most widely studied as chromatographic ligands, arginine has been successfully immobilized on different chromatographic supports (namely, agarose bead matrices, macroporous matrices, and monoliths) to achieve extra-pure gene therapy products. In this research, we studied the immobilization of arginine on 3DP chromatographic supports, evaluating the stability of the ligand/chromatographic support linkage under different chromatographic conditions to determine the robustness of these new prototypes. Moreover, we also applied plasmid DNA samples to these supports to observe the practical behaviour of the developed arginine 3DP chromatographic structures. Full article
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12 pages, 3239 KiB  
Article
Implementation of a New Electronic Liquid Dispensing System for Individualized Compounding of Hard Capsules
Pharmaceutics 2022, 14(8), 1580; https://doi.org/10.3390/pharmaceutics14081580 - 29 Jul 2022
Viewed by 1567
Abstract
An automated compounding device can be a useful tool for the rapid and accurate production of small batches for personalized medicine as well as for clinical batches. A novel electronic liquid dispensing system (ELDS) was investigated to produce hard capsules with individualized dose [...] Read more.
An automated compounding device can be a useful tool for the rapid and accurate production of small batches for personalized medicine as well as for clinical batches. A novel electronic liquid dispensing system (ELDS) was investigated to produce hard capsules with individualized dose strengths. An ethanol-based solvent system containing the antihypertensive enalapril maleate was extruded through a cannula into prefilled capsules. The capsules were prefilled with a powder bed of mesoporous silica (Syloid 244 FP) or synthetic dibasic calcium phosphate anhydrous (Fujicalin). The dosing accuracy as well as content uniformity of ELDS was compared with manual preparation using a Hamilton syringe (HS). Both methods met the pharmacopeia criteria for all formulations with an acceptance value (AV) less than 15. Drug adherence to the capsule shells was also investigated. A recovery rate of 98% of enalapril maleate showed almost no drug loss, but the appropriateness of the new dispensing method. Full article
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Review

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16 pages, 28257 KiB  
Review
A Review of the Benefits 3D Printing Brings to Patients with Neurological Diseases
Pharmaceutics 2023, 15(3), 892; https://doi.org/10.3390/pharmaceutics15030892 - 09 Mar 2023
Cited by 4 | Viewed by 2274
Abstract
This interdisciplinary review focuses on how flexible three-dimensional printing (3DP) technology can aid patients with neurological diseases. It covers a wide variety of current and possible applications ranging from neurosurgery to customizable polypill along with a brief description of the various 3DP techniques. [...] Read more.
This interdisciplinary review focuses on how flexible three-dimensional printing (3DP) technology can aid patients with neurological diseases. It covers a wide variety of current and possible applications ranging from neurosurgery to customizable polypill along with a brief description of the various 3DP techniques. The article goes into detail about how 3DP technology can aid delicate neurosurgical planning and its consequent outcome for patients. It also covers areas such as how the 3DP model can be utilized in patient counseling along with designing specific implants involved in cranioplasty and customization of a specialized instrument such as 3DP optogenetic probes. Furthermore, the review includes how a 3DP nasal cast can contribute to the development of nose-to-brain drug delivery along with looking into how bioprinting could be used for regenerating nerves and how 3D-printed drugs could offer practical benefits to patients suffering from neurological diseases via polypill. Full article
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