Special Issue "Additive Manufacturing Approaches to Produce Drug Delivery Systems"

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 (20 January 2022) | Viewed by 29002

Special Issue Editors

Prof. Dr. Nuno Alves
E-Mail Website
Guest Editor
Polytechnic Institute of Leiria, Centre for Rapid and Sustainable Product Development, Leiria, 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
Dr. Joana Valente
E-Mail Website
Guest Editor
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

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.

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

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Keywords

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

Published Papers (16 papers)

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Editorial

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Editorial
Editorial for Special Issue: “Additive Manufacturing Approaches to Produce Drug Delivery Systems”
Pharmaceutics 2022, 14(11), 2365; https://doi.org/10.3390/pharmaceutics14112365 - 02 Nov 2022
Viewed by 314
Abstract
Cutting-edge technologies such as additive manufacturing (AM) have had an enormous impact in a multitude of sectors [...] Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)

Research

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Article
Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing
Pharmaceutics 2022, 14(4), 871; https://doi.org/10.3390/pharmaceutics14040871 - 15 Apr 2022
Cited by 3 | Viewed by 1173
Abstract
Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim [...] Read more.
Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30–40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Fabricating High-Resolution and High-Dimensional Microneedle Mold through the Resolution Improvement of Stereolithography 3D Printing
Pharmaceutics 2022, 14(4), 766; https://doi.org/10.3390/pharmaceutics14040766 - 31 Mar 2022
Cited by 6 | Viewed by 1500
Abstract
Microneedles are transdermal drug delivery tools that can be fabricated simply, economically, and rapidly using SLA 3D printing. However, SLA 3D printing has a limitation in that the resolution is slightly lowered when the microneedle is precisely printed. To solve this issue, we [...] Read more.
Microneedles are transdermal drug delivery tools that can be fabricated simply, economically, and rapidly using SLA 3D printing. However, SLA 3D printing has a limitation in that the resolution is slightly lowered when the microneedle is precisely printed. To solve this issue, we optimized the SLA 3D printing conditions such as printing angle, needle height, aspect ratio, and spacing between the microneedles for high-resolution microneedle fabrication. The sharpest microneedle tip was obtained when the printing angle was adjusted to 60° in both the x and y axes. The aspect ratio and the spacing between the microneedles did not affect the output of the sharp tip. Under optimal conditions, the microneedles with 1180 ± 20 µm height, 490 ± 20 µm base, and 30.2 ± 3.4 µm tip diameter were obtained. The dissolving microneedle patch, prepared using the 3D printed microneedle as a mold, penetrated the porcine skin ex vivo. When the printing angle was 60° in the x and y axes, the area of the single stacking layer, including the microneedle tip, increased, and thus the sharp tip could be printed. A high-dimensional, side-notched arrowhead (SNA) microneedle was fabricated by applying the SLA 3D printing condition. Moreover, a letter-type microneedle patch was fabricated using the customized characteristics of 3D printing. Consequently, high-resolution and high-dimensional microneedles were successfully fabricated by adjusting the printing angle using a general SLA 3D printer, and this technology will be applied to the manufacture of drug delivery tools and various microstructures. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Thermal, Mechanical and Biocompatibility Analyses of Photochemically Polymerized PEGDA250 for Photopolymerization-Based Manufacturing Processes
Pharmaceutics 2022, 14(3), 628; https://doi.org/10.3390/pharmaceutics14030628 - 12 Mar 2022
Cited by 4 | Viewed by 1314
Abstract
Novel fabrication techniques based on photopolymerization enable the preparation of complex multi-material constructs for biomedical applications. This requires an understanding of the influence of the used reaction components on the properties of the generated copolymers. The identification of fundamental characteristics of these copolymers [...] Read more.
Novel fabrication techniques based on photopolymerization enable the preparation of complex multi-material constructs for biomedical applications. This requires an understanding of the influence of the used reaction components on the properties of the generated copolymers. The identification of fundamental characteristics of these copolymers is necessary to evaluate their potential for biomaterial applications. Additionally, knowledge of the properties of the starting materials enables subsequent tailoring of the biomaterials to meet individual implantation needs. In our study, we have analyzed the biological, chemical, mechanical and thermal properties of photopolymerized poly(ethyleneglycol) diacrylate (PEGDA) and specific copolymers with different photoinitiator (PI) concentrations before and after applying a post treatment washing process. As comonomers, 1,3-butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate were used. The in vitro studies confirm the biocompatibility of all investigated copolymers. Uniaxial tensile tests show significantly lower tensile strength (82% decrease) and elongation at break (76% decrease) values for washed samples. Altered tensile strength is also observed for different PI concentrations: on average, 6.2 MPa for 1.25% PI and 3.1 MPa for 0.5% PI. The addition of comonomers lowers elongation at break on average by 45%. Moreover, our observations show glass transition temperatures (Tg) ranging from 27 °C to 56 °C, which significantly increase with higher comonomer content. These results confirm the ability to generate biocompatible PEGDA copolymers with specific thermal and mechanical properties. These can be considered as resins for various additive manufacturing-based applications to obtain personalized medical devices, such as drug delivery systems (DDS). Therefore, our study has advanced the understanding of PEGDA multi-materials and will contribute to the future development of tools ensuring safe and effective individual therapy for patients. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Blind-Watermarking—Proof-of-Concept of a Novel Approach to Ensure Batch Traceability for 3D Printed Tablets
Pharmaceutics 2022, 14(2), 432; https://doi.org/10.3390/pharmaceutics14020432 - 17 Feb 2022
Cited by 1 | Viewed by 1172
Abstract
Falsified medicines are a major issue and a threat around the world. Various approaches are currently being investigated to mitigate the threat. In this study, a concept is tested that encodes binary digits (bits) on the surface of Fused Deposition Modelling (FDM) 3D [...] Read more.
Falsified medicines are a major issue and a threat around the world. Various approaches are currently being investigated to mitigate the threat. In this study, a concept is tested that encodes binary digits (bits) on the surface of Fused Deposition Modelling (FDM) 3D printed geometries. All that is needed is a computer, a FDM 3D printer and a paper scanner for detection. For the experiments, eleven different formulations were tested, covering the most used polymers for 3D printing in pharma: Ethylene-vinyl acetate (EVA), polyvinyl alcohol (PVA), polylactic acid (PLA), Hypromellose (HPMC), ethyl cellulose (EC), basic butylated-methacrylate-copolymer (EPO), and ammonio-methacrylate-copolymer type A (ERL). In addition, the scanning process and printing process were evaluated. It was possible to print up to 32 bits per side on oblong shaped tablets corresponding to the dimensions of market preparations of oblong tablets and capsules. Not all polymers or polymer blends were suitable for this method. Only PVA, PLA, EC, EC+HPMC, and EPO allowed the detection of bits with the scanner. EVA and ERL had too much surface roughness, too low viscosity, and cooled down too slowly preventing the detection of bits. It was observed that the addition of a colorant or active pharmaceutical ingredient (API) could facilitate the detection process. Thus, the process could be transferred for 3D printed pharmaceuticals, but further improvement is necessary to increase robustness and allow use for more materials. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Multifunctional Gelatin/Chitosan Electrospun Wound Dressing Dopped with Undaria pinnatifida Phlorotannin-Enriched Extract for Skin Regeneration
Pharmaceutics 2021, 13(12), 2152; https://doi.org/10.3390/pharmaceutics13122152 - 14 Dec 2021
Cited by 7 | Viewed by 1819
Abstract
The similarities of electrospun fibers with the skin extracellular matrix (ECM) make them promising structures for advanced wound dressings. Moreover, infection and resistance in wounds are a major health concern that may be reduced with antibacterial wound dressings. In this work, a multifunctional [...] Read more.
The similarities of electrospun fibers with the skin extracellular matrix (ECM) make them promising structures for advanced wound dressings. Moreover, infection and resistance in wounds are a major health concern that may be reduced with antibacterial wound dressings. In this work, a multifunctional wound dressing was developed based on gelatin/chitosan hybrid fibers dopped with phlorotannin-enrich extract from the seaweed Undaria pinnatifida. The intrinsic electrospun structure properties combined with the antimicrobial and anti-inflammatory properties of phlorotannin-enrich extract will enhance the wound healing process. Electrospun meshes were produced by incorporating 1 or 2 wt% of extract, and the structure without extract was used as a control. Physico-chemical, mechanical, and biological properties were evaluated for all conditions. Results demonstrated that all developed samples presented a homogenous fiber deposition with the average diameters closer to the native ECM fibrils, and high porosities (~90%) that will be crucial to control the wound moist environment. According to the tensile test assays, the incorporation of phlorotannin-enriched extract enhances the elastic performance of the samples. Additionally, the extract incorporation made the structure stable over time since its in vitro degradation rates decreased under enzymatic medium. Extract release profile demonstrated a longstanding delivery (up to 160 days), reaching a maximum value of ~98% over time. Moreover, the preliminary antimicrobial results confirm the mesh’s antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. In terms of biological characterization, no condition presented cytotoxicity effects on hDNF cells, allowing their adhesion and proliferation over 14 days, except the condition of 2 wt% after 7 days. Overall, the electrospun structure comprising phlorotannins-enriched extract is a promising bioactive structure with potential to be used as a drug delivery system for skin regeneration by reducing the bacterial infection in the wound bed. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Controlled and Local Delivery of Antibiotics by 3D Core/Shell Printed Hydrogel Scaffolds to Treat Soft Tissue Infections
Pharmaceutics 2021, 13(12), 2151; https://doi.org/10.3390/pharmaceutics13122151 - 14 Dec 2021
Cited by 4 | Viewed by 1873
Abstract
Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with [...] Read more.
Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot (in the core composed of low concentrated biomaterial ink 3% alginate) surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink (composed of alginate and methylcellulose or alginate, methylcellulose and Laponite) retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
3D Printed Buccal Films for Prolonged-Release of Propranolol Hydrochloride: Development, Characterization and Bioavailability Prediction
Pharmaceutics 2021, 13(12), 2143; https://doi.org/10.3390/pharmaceutics13122143 - 13 Dec 2021
Cited by 8 | Viewed by 2246
Abstract
Gelatin-polyvinylpyrrolidone (PVP) and gelatin-poly(vinyl alcohol) (PVA) mucoadhesive buccal films loaded with propranolol hydrochloride (PRH) were prepared by semi-solid extrusion 3D printing. The aim of this study was to evaluate the effects of the synthetic polymers PVP and PVA on thermal and mechanical properties [...] Read more.
Gelatin-polyvinylpyrrolidone (PVP) and gelatin-poly(vinyl alcohol) (PVA) mucoadhesive buccal films loaded with propranolol hydrochloride (PRH) were prepared by semi-solid extrusion 3D printing. The aim of this study was to evaluate the effects of the synthetic polymers PVP and PVA on thermal and mechanical properties and drug release profiles of gelatin-based films. The Fourier-transform infrared spectroscopy showed that hydrogen bonding between gelatin and PVP formed during printing. In the other blend, neither the esterification of PVA nor gelatin occurred. Differential scanning calorimetry revealed the presence of partial helical structures. In line with these results, the mechanical properties and drug release profiles were different for each blend. Formulation with gelatin-PVP and PRH showed higher tensile strength, hardness, and adhesive strength but slower drug release than formulation with gelatin-PVA and PRH. The in silico population simulations indicated increased drug bioavailability and decreased inter-individual variations in the resulting pharmacokinetic profiles compared to immediate-release tablets. Moreover, the simulation results suggested that reduced PRH daily dosing can be achieved with prolonged-release buccal films, which improves patient compliance. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Development of Antimicrobial Nitric Oxide-Releasing Fibers
Pharmaceutics 2021, 13(9), 1445; https://doi.org/10.3390/pharmaceutics13091445 - 10 Sep 2021
Cited by 2 | Viewed by 1112
Abstract
Nitric oxide (NO) is a highly reactive gas molecule, exhibiting antimicrobial properties. Because of its reactive nature, it is challenging to store and deliver NO efficiently as a therapeutic agent. The objective of this study was to develop NO-releasing polymeric fibers (NO-fibers), as [...] Read more.
Nitric oxide (NO) is a highly reactive gas molecule, exhibiting antimicrobial properties. Because of its reactive nature, it is challenging to store and deliver NO efficiently as a therapeutic agent. The objective of this study was to develop NO-releasing polymeric fibers (NO-fibers), as an effective delivery platform for NO. NO-fibers were fabricated with biopolymer solutions of polyvinyl pyrrolidone (PVP) and ethylcellulose (EC), and derivatives of N-diazeniumdiolate (NONOate) as NO donor molecules, using an electrospinning system. We evaluated in vitro NO release kinetics, along with antimicrobial effects and cytotoxicity in microorganisms and human cell culture models. We also studied the long-term stability of NONOates in NO-fibers over 12 months. We demonstrated that the NO-fibers could release NO over 24 h, and showed inhibition of the growth of Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA), without causing cytotoxicity in human cells. NO-fibers were able to store NONOates for over 12 months at room temperature. This study presents the development of NO-fibers, and the feasibility of NO-fibers to efficiently store and deliver NO, which can be further developed as a bandage. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Design of Experiments to Achieve an Efficient Chitosan-Based DNA Vaccine Delivery System
Pharmaceutics 2021, 13(9), 1369; https://doi.org/10.3390/pharmaceutics13091369 - 31 Aug 2021
Cited by 5 | Viewed by 1455
Abstract
In current times, DNA vaccines are seen as a promising approach to treat and prevent diseases, such as virus infections and cancer. Aiming at the production of a functional and effective plasmid DNA (pDNA) delivery system, four chitosan polymers, differing in the molecular [...] Read more.
In current times, DNA vaccines are seen as a promising approach to treat and prevent diseases, such as virus infections and cancer. Aiming at the production of a functional and effective plasmid DNA (pDNA) delivery system, four chitosan polymers, differing in the molecular weight, were studied using the design of experiments (DoE) tool. These gene delivery systems were formulated by ionotropic gelation and exploring the chitosan and TPP concentrations as DoE inputs to maximize the nanoparticle positive charge and minimize their size and polydispersity index (PDI) as DoE outputs. The obtained linear and quadratic models were statistically significant (p-value < 0.05) and non-significant lack of fit, with suitable coefficient of determination and the respective optimal points successfully validated. Furthermore, morphology, stability and cytotoxicity assays were performed to evaluate the endurance of these systems over time and their further potential for future in vitro studies. The subsequent optimization process was successful achieved for the delivery systems based on the four chitosan polymers, in which the smallest particle size was obtained for the carrier containing the 5 kDa chitosan (~82 nm), while the nanosystem prepared with the high molecular weight (HMW) chitosan displayed the highest zeta potential (~+26.8 mV). Delivery systems were stable in the formulation buffer after a month and did not exhibit toxicity for the cells. In this sense, DoE revealed to be a powerful tool to explore and tailor the characteristics of chitosan/pDNA nanosystems significantly contributing to unraveling an optimum carrier for advancing the DNA vaccines delivery field. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Medicated Hydroxyapatite/Collagen Hybrid Scaffolds for Bone Regeneration and Local Antimicrobial Therapy to Prevent Bone Infections
Pharmaceutics 2021, 13(7), 1090; https://doi.org/10.3390/pharmaceutics13071090 - 16 Jul 2021
Cited by 8 | Viewed by 1834
Abstract
Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In [...] Read more.
Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bioresorbable bone graft was designed and investigated for its ability to control antibiotic drug release in situ. This represents an ideal solution for the eradication or prevention of infection, while simultaneously repairing bone defects. Vancomycin hydrochloride and gentamicin sulfate, here considered for testing, were loaded into a previously developed and largely investigated hybrid bone-mimetic scaffold made of collagen fibers biomineralized with magnesium doped-hydroxyapatite (MgHA/Coll), which in the last ten years has widely demonstrated its effective potential in bone tissue regeneration. Here, we have explored whether it can be used as a controlled local delivery system for antibiotic drugs. An easy loading method was selected in order to be reproducible, quickly, in the operating room. The maintenance of the antibacterial efficiency of the released drugs and the biosafety of medicated scaffolds were assessed with microbiological and in vitro tests, which demonstrated that the MgHA/Coll scaffolds were safe and effective as a local delivery system for an extended duration therapy—promising results for the prevention of bone defect-related infections in orthopedic surgeries. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
3D Printing of Dapagliflozin Containing Self-Nanoemulsifying Tablets: Formulation Design and In Vitro Characterization
Pharmaceutics 2021, 13(7), 993; https://doi.org/10.3390/pharmaceutics13070993 - 30 Jun 2021
Cited by 12 | Viewed by 2426
Abstract
The 3D printing techniques have been explored extensively in recent years for pharmaceutical manufacturing and drug delivery applications. The current investigation aims to explore 3D printing for the design and development of a nanomedicine-based oral solid dosage form of a poorly water-soluble drug. [...] Read more.
The 3D printing techniques have been explored extensively in recent years for pharmaceutical manufacturing and drug delivery applications. The current investigation aims to explore 3D printing for the design and development of a nanomedicine-based oral solid dosage form of a poorly water-soluble drug. A self-nanoemulsifying tablet formulation of dapagliflozin propanediol monohydrate was developed utilizing the semisolid pressure-assisted microsyringe (PAM) extrusion-based 3D printing technique. The developed formulation system consists of two major components (liquid and solid phase), which include oils (caproyl 90, octanoic acid) and co-surfactant (PEG 400) as liquid phase while surfactant (poloxamer 188) and solid matrix (PEG 6000) as solid-phase excipients that ultimately self-nanoemulsify as a drug encapsulated nanoemulsion system on contact with aqueous phase/gastrointestinal fluid. The droplet size distribution of the generated nanoemulsion from a self-nanoemulsifying 3D printed tablet was observed to be 104.7 ± 3.36 nm with polydispersity index 0.063 ± 0.024. The FT-IR analysis of the printed tablet revealed that no drug-excipients interactions were observed. The DSC and X-RD analysis of the printed tablet revealed that the loaded drug is molecularly dispersed in the crystal lattice of the tablet solid matrix and remains solubilized in the liquid phase of the printed tablet. SEM image of the drug-loaded self-nanoemulsifying tablets revealed that dapagliflozin propanediol monohydrate was completely encapsulated in the solid matrix of the printed tablet, which was further confirmed by SEM-EDS analysis. The in vitro dissolution profile of dapagliflozin-loaded self-nanoemulsifying tablet revealed an immediate-release drug profile for all three sizes (8 mm, 10 mm, and 12 mm) tablets, exhibiting >75.0% drug release within 20 min. Thus, this study has emphasized the capability of the PAM-based 3D printing technique to print a self-nanoemulsifying tablet dosage form with an immediate-release drug profile for poorly water-soluble drug. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Article
Elastic Bioresorbable Polymeric Capsules for Osmosis-Driven Delayed Burst Delivery of Vaccines
Pharmaceutics 2021, 13(3), 434; https://doi.org/10.3390/pharmaceutics13030434 - 23 Mar 2021
Cited by 2 | Viewed by 1770
Abstract
Single-administration vaccine delivery systems are intended to improve the efficiency and efficacy of immunisation programs in both human and veterinary medicine. In this work, an osmotically triggered delayed delivery device was developed that was able to release a payload after a delay of [...] Read more.
Single-administration vaccine delivery systems are intended to improve the efficiency and efficacy of immunisation programs in both human and veterinary medicine. In this work, an osmotically triggered delayed delivery device was developed that was able to release a payload after a delay of approximately 21 days, in a consistent and reproducible manner. The device was constructed out of a flexible poly(ε-caprolactone) photo-cured network fabricated into a hollow tubular shape, which expelled approximately 10% of its total payload within 2 days after bursting. Characterisation of the factors that control the delay of release demonstrated that it was advantageous to adjust material permeability and device wall thickness over manipulation of the osmogent concentration in order to maintain reproducibility in burst delay times. The photo-cured poly(ε-caprolactone) network was shown to be fully degradable in vitro, and there was no evidence of cytotoxicity after 11 days of direct contact with primary dermal fibroblasts. This study provides strong evidence to support further development of flexible biomaterials with the aim of continuing improvement of the device burst characteristics in order to provide the greatest chance of the devices succeeding with in vivo vaccine booster delivery. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Review

Jump to: Editorial, Research

Review
Solid Dispersion Formulations by FDM 3D Printing—A Review
Pharmaceutics 2022, 14(4), 690; https://doi.org/10.3390/pharmaceutics14040690 - 23 Mar 2022
Cited by 3 | Viewed by 1769
Abstract
Additive manufacturing (AM) is revolutionizing the way medicines are designed, manufactured, and utilized. Perhaps, AM appears to be ideal for the fit-for-purpose manufacturing of medicines in contrast to the several disadvantages associated with the conventional fit-for-all mass production that accounts for less than [...] Read more.
Additive manufacturing (AM) is revolutionizing the way medicines are designed, manufactured, and utilized. Perhaps, AM appears to be ideal for the fit-for-purpose manufacturing of medicines in contrast to the several disadvantages associated with the conventional fit-for-all mass production that accounts for less than 50% of pharmacotherapeutic treatment/management of diseases especially among children and elderly patients, as well as patients with special needs. In this review, we discuss the current trends in the application of additive manufacturing to prepare personalized dosage forms on-demand focusing the attention on the relevance of coupling solid dispersion with FDM 3D printing. Combining the two technologies could offer many advantages such as to improve the solubility, dissolution, and oral bioavailability of poorly soluble drugs in tandem with the concept of precision medicine and personalized dosing and to address the dilemma of commercial availability of FDM filaments loaded with Class II and/or Class IV drugs. However, thermal treatment especially for heat-sensitive drugs, regulatory, and ethical obligations in terms of quality control and quality assurance remain points of concern. Hence, a concerted effort is needed between the scientific community, the pharmaceutical industries, the regulatory agencies, the clinicians and clinical pharmacists, and the end-users to address these concerns. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Review
Current Trends on Protein Driven Bioinks for 3D Printing
Pharmaceutics 2021, 13(9), 1444; https://doi.org/10.3390/pharmaceutics13091444 - 10 Sep 2021
Cited by 8 | Viewed by 2177
Abstract
In the last decade, three-dimensional (3D) extrusion bioprinting has been on the top trend for innovative technologies in the field of biomedical engineering. In particular, protein-based bioinks such as collagen, gelatin, silk fibroin, elastic, fibrin and protein complexes based on decellularized extracellular matrix [...] Read more.
In the last decade, three-dimensional (3D) extrusion bioprinting has been on the top trend for innovative technologies in the field of biomedical engineering. In particular, protein-based bioinks such as collagen, gelatin, silk fibroin, elastic, fibrin and protein complexes based on decellularized extracellular matrix (dECM) are receiving increasing attention. This current interest is the result of protein’s tunable properties, biocompatibility, environmentally friendly nature and possibility to provide cells with the adequate cues, mimicking the extracellular matrix’s function. In this review we describe the most relevant stages of the development of a protein-driven bioink. The most popular formulations, molecular weights and extraction methods are covered. The different crosslinking methods used in protein bioinks, the formulation with other polymeric systems or molecules of interest as well as the bioprinting settings are herein highlighted. The cell embedding procedures, the in vitro, in vivo, in situ studies and final applications are also discussed. Finally, we approach the development and optimization of bioinks from a sequential perspective, discussing the relevance of each parameter during the pre-processing, processing, and post-processing stages of technological development. Through this approach the present review expects to provide, in a sequential manner, helpful methodological guidelines for the development of novel bioinks. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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Review
Selective Laser Sintering (SLS), a New Chapter in the Production of Solid Oral Forms (SOFs) by 3D Printing
Pharmaceutics 2021, 13(8), 1212; https://doi.org/10.3390/pharmaceutics13081212 - 06 Aug 2021
Cited by 19 | Viewed by 3141
Abstract
3D printing is a new emerging technology in the pharmaceutical manufacturing landscape. Its potential advantages for personalized medicine have been widely explored and commented on in the literature over recent years. More recently, the selective laser sintering (SLS) technique has been investigated for [...] Read more.
3D printing is a new emerging technology in the pharmaceutical manufacturing landscape. Its potential advantages for personalized medicine have been widely explored and commented on in the literature over recent years. More recently, the selective laser sintering (SLS) technique has been investigated for oral drug-delivery applications. Thus, this article reviews the work that has been conducted on SLS 3D printing for the preparation of solid oral forms (SOFs) from 2017 to 2020 and discusses the opportunities and challenges for this state-of-the-art technology in precision medicine. Overall, the 14 research articles reviewed report the use of SLS printers equipped with a blue diode laser (445–450 nm). The review highlights that the printability of pharmaceutical materials, although an important aspect for understanding the sintering process has only been properly explored in one article. The modulation of the porosity of printed materials appears to be the most interesting outcome of this technology for pharmaceutical applications. Generally, SLS shows great potential to improve compliance within fragile populations. The inclusion of “Quality by Design” tools in studies could facilitate the deployment of SLS in clinical practice, particularly where Good Manufacturing Practices (GMPs) for 3D-printing processes do not currently exist. Nevertheless, drug stability and powder recycling remain particularly challenging in SLS. These hurdles could be overcome by collaboration between pharmaceutical industries and compounding pharmacies. Full article
(This article belongs to the Special Issue Additive Manufacturing Approaches to Produce Drug Delivery Systems)
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