Printed Pharmaceuticals in Future Healthcare

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 May 2022) | Viewed by 28261

Special Issue Editors


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Guest Editor
Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: additive manufacturing; 3D printing; 2D printing; oral delivery; buccal delivery; permeation; mucoadhesion

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Guest Editor
Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: 3D printing; cannabinoids; wound healing; polymer science; material science

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Guest Editor
Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: pharmaceutical nanotechnology; mucosal delivery; poorly soluble drugs; additive manufacturing
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Special Issue Information

Dear Colleagues,

3D printing technologies have rapidly shown their great potential in revolutionizing conventional procedures in pharmaceutical manufacturing, which helps to conceive various patient-centric approaches in a dynamic healthcare environment.  The operating principles of these technologies are key in the development of novel and more flexible drug delivery systems. Thus, different methods, materials, and structural properties of these formulations need to be considered. Furthermore, we need to explore new approaches to introducing these systems into distributed points-of-care, in order to succeed with on-site and safe production and delivery to the patient. In this context, the recent trends in coupling 3D printing with state-of-the-art manufacturing technologies and digital tools can facilitate the optimization of pharmaceutical products, as well as the integration of cross-communication platforms between all involved parties, including the patient, the manufacturing hub, and the healthcare professional.

This Special Issue will cover all aspects of 3D printing strategies for fabricating novel drug delivery systems and future directions for utilizing state-of-the-art technologies, in our quest to improve patients’ well-being in the forthcoming era of a personalized healthcare environment.

Dr. Georgios Eleftheriadis
Dr. Eleftherios G. Andriotis
Prof. Dr. Dimitrios G. Fatouros
Guest Editors

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Keywords

  • 3D printing
  • formulations and drug delivery systems
  • personalized treatments
  • future healthcare
  • digital technologies
  • distributed manufacturing

Published Papers (8 papers)

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Research

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22 pages, 5707 KiB  
Article
Analysis of NSAIDs in Rat Plasma Using 3D-Printed Sorbents by LC-MS/MS: An Approach to Pre-Clinical Pharmacokinetic Studies
by Daya Raju Adye, Sachin B. Jorvekar, Upadhyayula Suryanarayana Murty, Subham Banerjee and Roshan M. Borkar
Pharmaceutics 2023, 15(3), 978; https://doi.org/10.3390/pharmaceutics15030978 - 18 Mar 2023
Cited by 4 | Viewed by 1416
Abstract
Analytical sample preparation techniques are essential for assessing chemicals in various biological matrices. The development of extraction techniques is a modern trend in the bioanalytical sciences. We fabricated customized filaments using hot-melt extrusion techniques followed by fused filament fabrication-mediated 3D printing technology to [...] Read more.
Analytical sample preparation techniques are essential for assessing chemicals in various biological matrices. The development of extraction techniques is a modern trend in the bioanalytical sciences. We fabricated customized filaments using hot-melt extrusion techniques followed by fused filament fabrication-mediated 3D printing technology to rapidly prototype sorbents that extract non-steroidal anti-inflammatory drugs from rat plasma for determining pharmacokinetic profiles. The filament was prototyped as a 3D-printed sorbent for extracting small molecules using AffinisolTM, polyvinyl alcohol, and triethyl citrate. The optimized extraction procedure and parameters influencing the sorbent extraction were systematically investigated by the validated LC-MS/MS method. Furthermore, a bioanalytical method was successfully implemented after oral administration to determine the pharmacokinetic profiles of indomethacin and acetaminophen in rat plasma. The Cmax was found to be 0.33 ± 0.04 µg/mL and 27.27 ± 9.9 µg/mL for indomethacin and acetaminophen, respectively, at the maximum time (Tmax) (h) of 0.5–1 h. The mean area under the curve (AUC0–t) for indomethacin was 0.93 ± 0.17 µg h/mL, and for acetaminophen was 32.33± 10.8 µg h/mL. Owing to their newly customizable size and shape, 3D-printed sorbents have opened new opportunities for extracting small molecules from biological matrices in preclinical studies. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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24 pages, 5454 KiB  
Article
Fabrication and Preliminary In Vitro Evaluation of 3D-Printed Alginate Films with Cannabidiol (CBD) and Cannabigerol (CBG) Nanoparticles for Potential Wound-Healing Applications
by Paraskevi Kyriaki Monou, Anastasia Maria Mamaligka, Emmanuil K. Tzimtzimis, Dimitrios Tzetzis, Souzan Vergkizi-Nikolakaki, Ioannis S. Vizirianakis, Eleftherios G. Andriotis, Georgios K. Eleftheriadis and Dimitrios G. Fatouros
Pharmaceutics 2022, 14(8), 1637; https://doi.org/10.3390/pharmaceutics14081637 - 05 Aug 2022
Cited by 10 | Viewed by 2862
Abstract
In this study, drug carrier nanoparticles comprised of Pluronic-F127 and cannabidiol (CBD) or cannabigerol (CBG) were developed, and their wound healing action was studied. They were further incorporated in 3D printed films based on sodium alginate. The prepared films were characterized morphologically and [...] Read more.
In this study, drug carrier nanoparticles comprised of Pluronic-F127 and cannabidiol (CBD) or cannabigerol (CBG) were developed, and their wound healing action was studied. They were further incorporated in 3D printed films based on sodium alginate. The prepared films were characterized morphologically and physicochemically and used to evaluate the drug release profiles of the nanoparticles. Additional studies on their water loss rate, water retention capacity, and 3D-printing shape fidelity were performed. Nanoparticles were characterized physicochemically and for their drug loading performance. They were further assessed for their cytotoxicity (MTT Assay) and wound healing action (Cell Scratch Assay). The in vitro wound-healing study showed that the nanoparticles successfully enhanced wound healing in the first 6 h of application, but in the following 6 h they had an adverse effect. MTT assay studies revealed that in the first 24 h, a concentration of 0.1 mg/mL nanoparticles resulted in satisfactory cell viability, whereas CBG nanoparticles were safe even at 48 h. However, in higher concentrations and after a threshold of 24 h, the cell viability was significantly decreased. The results also presented mono-disperse nano-sized particles with diameters smaller than 200 nm with excellent release profiles and enhanced thermal stability. Their entrapment efficiency and drug loading properties were higher than 97%. The release profiles of the active pharmaceutical ingredients from the films revealed a complete release within 24 h. The fabricated 3D-printed films hold promise for wound healing applications; however, more studies are needed to further elucidate their mechanism of action. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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21 pages, 3997 KiB  
Article
Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model
by Marijana Madžarević, Đorđe Medarević, Stefan Pavlović, Branka Ivković, Jelena Đuriš and Svetlana Ibrić
Pharmaceutics 2021, 13(11), 1969; https://doi.org/10.3390/pharmaceutics13111969 - 20 Nov 2021
Cited by 13 | Viewed by 2565
Abstract
Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics [...] Read more.
Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors, ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR results revealed that there was no interaction between irbesartan and the applied excipients. DSC results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding lactose monohydrate enabled faster drug release while reducing the possibility for printing with different laser speeds. However, formulations with crospovidone were printable with a wider range of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however, it needs to be governed by the composition of the whole formulation. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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19 pages, 7527 KiB  
Article
3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs
by Christos S. Katsiotis, Michelle Åhlén, Maria Strømme and Ken Welch
Pharmaceutics 2021, 13(7), 1096; https://doi.org/10.3390/pharmaceutics13071096 - 18 Jul 2021
Cited by 17 | Viewed by 3921
Abstract
Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and [...] Read more.
Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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16 pages, 1929 KiB  
Article
Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing
by Xabier Mendibil, Gaizka Tena, Alaine Duque, Nerea Uranga, Miguel Ángel Campanero and Jesús Alonso
Pharmaceutics 2021, 13(6), 907; https://doi.org/10.3390/pharmaceutics13060907 - 19 Jun 2021
Cited by 16 | Viewed by 4119
Abstract
Three-dimensional printed drug development is nowadays an active area in the pharmaceutical industry, where the search for an appropriate edible carrier that permits the thermal processing of the mixture at temperature levels that are safe for the drug is an important field of [...] Read more.
Three-dimensional printed drug development is nowadays an active area in the pharmaceutical industry, where the search for an appropriate edible carrier that permits the thermal processing of the mixture at temperature levels that are safe for the drug is an important field of study. Here, potato starch and hydroxypropyl cellulose based mixtures loaded with paracetamol up to 50% in weight were processed by hot melt extrusion at 85 °C to test their suitability to be thermally processed. The extruded mixtures were tested by liquid chromatography to analyze their release curves and were thermally characterized. The drug recovery was observed to be highly dependent on the initial moisture level of the mixture, the samples being prepared with an addition of water at a ratio of 3% in weight proportional to the starch amount, highly soluble and easy to extrude. The release curves showed a slow and steady drug liberation compared to a commercially available paracetamol tablet, reaching the 100% of recovery at 60 min. The samples aged for 6 weeks showed slower drug release curves compared to fresh samples, this effect being attributable to the loss of moisture. The paracetamol loaded mixture in powder form was used to print pills with different sizes and geometries in a fused deposition modelling three-dimensional printer modified with a commercially available powder extrusion head, showing the potential of this formulation for use in personalized medicine. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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13 pages, 3249 KiB  
Article
Supercritical Fluid Technology for the Development of 3D Printed Controlled Drug Release Dosage Forms
by Johannes Schmid, Martin A. Wahl and Rolf Daniels
Pharmaceutics 2021, 13(4), 543; https://doi.org/10.3390/pharmaceutics13040543 - 13 Apr 2021
Cited by 5 | Viewed by 2050
Abstract
Supercritical CO2 loading of preformed 3D printed drug carriers with active pharmaceutical ingredients (APIs) shows great potential in the development of oral dosage forms for future personalized medicine. We designed 3D printed scaffold like drug carriers with varying pore sizes made from [...] Read more.
Supercritical CO2 loading of preformed 3D printed drug carriers with active pharmaceutical ingredients (APIs) shows great potential in the development of oral dosage forms for future personalized medicine. We designed 3D printed scaffold like drug carriers with varying pore sizes made from polylactic acid (PLA) using a fused deposition modelling (FDM) 3D printer. The 3D printed drug carriers were then loaded with Ibuprofen as a model drug, employing the controlled particle deposition (CPD) process from supercritical CO2. Carriers with varying pore sizes (0.027–0.125 mm) were constructed and loaded with Ibuprofen to yield drug-loaded carriers with a total amount of 0.83–2.67 mg API (0.32–1.41% w/w). Dissolution studies of the carriers show a significantly decreasing dissolution rate with decreasing pore sizes with a mean dissolution time (MDT) of 8.7 min for the largest pore size and 128.2 min for the smallest pore size. The API dissolution mechanism from the carriers was determined to be Fickian diffusion from the non-soluble, non-swelling carriers. Using 3D printing in combination with the CPD process, we were able to develop dosage forms with individually tailored controlled drug release. The dissolution rate of our dosage forms can be easily adjusted to the individual needs by modifying the pore sizes of the 3D printed carriers. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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Review

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17 pages, 2688 KiB  
Review
The Advent of a New Era in Digital Healthcare: A Role for 3D Printing Technologies in Drug Manufacturing?
by Ioannis I. Andreadis, Christos I. Gioumouxouzis, Georgios K. Eleftheriadis and Dimitrios G. Fatouros
Pharmaceutics 2022, 14(3), 609; https://doi.org/10.3390/pharmaceutics14030609 - 10 Mar 2022
Cited by 27 | Viewed by 4561 | Correction
Abstract
The technological revolution has physically affected all manufacturing domains, at the gateway of the fourth industrial revolution. Three-dimensional (3D) printing has already shown its potential in this new reality, exhibiting remarkable applications in the production of drug delivery systems. As part of this [...] Read more.
The technological revolution has physically affected all manufacturing domains, at the gateway of the fourth industrial revolution. Three-dimensional (3D) printing has already shown its potential in this new reality, exhibiting remarkable applications in the production of drug delivery systems. As part of this concept, personalization of the dosage form by means of individualized drug dose or improved formulation functionalities has concentrated global research efforts. Beyond the manufacturing level, significant parameters must be considered to promote the real-time manufacturing of pharmaceutical products in distributed areas. The majority of current research activities is focused on formulating 3D-printed drug delivery systems while showcasing different scenarios of installing 3D printers in patients’ houses, hospitals, and community pharmacies, as well as in pharmaceutical industries. Such research presents an array of parameters that must be considered to integrate 3D printing in a future healthcare system, with special focus on regulatory issues, drug shortages, quality assurance of the product, and acceptability of these scenarios by healthcare professionals and public parties. The objective of this review is to critically present the spectrum of possible scenarios of 3D printing implementation in future healthcare and to discuss the inevitable issues that must be addressed. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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27 pages, 6328 KiB  
Review
3D Printing of Thermo-Sensitive Drugs
by Sadikalmahdi Abdella, Souha H. Youssef, Franklin Afinjuomo, Yunmei Song, Paris Fouladian, Richard Upton and Sanjay Garg
Pharmaceutics 2021, 13(9), 1524; https://doi.org/10.3390/pharmaceutics13091524 - 21 Sep 2021
Cited by 24 | Viewed by 5297
Abstract
Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of [...] Read more.
Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
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