Recent Non-oral Dosage Form Development: Focus on 3D-Printed Formulations

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (30 July 2023) | Viewed by 11173

Special Issue Editor

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany
Interests: 3D printed formulations; parenteral dosage forms; intravitreal dosage forms; implants; bio-relevant dissolution testing

Special Issue Information

Dear Colleagues,

With the advancement of 3D printing techniques during the last decade, many new production opportunities have arisen which might also be used to produce medicinal products and drug-containing medical devices. Furthermore, the concept of individualized medicines requires the development of new production strategies in the pharmaceutical field. This is especially true for many non-oral dosage forms which are often produced in smaller batch sizes and in some cases require individualized shapes due to the anatomical variability of the site of implantation. Since many traditional concepts regarding the manufacturing but also quality control of these products cannot be directly applied, a lot of research is necessary to bring 3D printed non-oral dosage forms to the patients in the near future.

I am pleased to invite you to contribute a manuscript to the Special Issue “Recent Non-oral Dosage Form Development: Focus on 3D-Printed Formulations” of Pharmaceutics. This Special Issue aims to focus on the development of 3D printing techniques and also methods to characterize 3D printed drug-containing products in the field of non-oral medical devices and medicinal products. The dosage forms contain but are not limited to implants for different sites of administration such as classical intramuscular or subcutaneous sites but also intravitreal or further more specified sites in the human or animal body. The dosage forms may be intended exclusively for drug delivery or they might also contain a drug to be delivered to aid in the main function which is not pharmacologically, e.g., to keep a previously occluded lumen patent or to regulate foreign body reaction to a functional implant. In this Special Issue, original research articles and reviews on new aspects of 3D printing of non-oral dosage forms as well as characterization techniques or input regarding regulatory pathways are welcome.

I look forward to receiving your contributions. 

Prof. Dr. Anne Seidlitz 
Guest Editor

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Keywords

  • 3D printing
  • parenteral dosage forms
  • implants
  • medical devices
  • medicinal products
  • dosage form development
  • analysis of 3D printed dosage forms
  • regulation of 3D printed products

Published Papers (6 papers)

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Research

19 pages, 10032 KiB  
Article
3D Printing of Personalised Carvedilol Tablets Using Selective Laser Sintering
by Atabak Ghanizadeh Tabriz, Quentin Gonot-Munck, Arnaud Baudoux, Vivek Garg, Richard Farnish, Orestis L. Katsamenis, Ho-Wah Hui, Nathan Boersen, Sandra Roberts, John Jones and Dennis Douroumis
Pharmaceutics 2023, 15(9), 2230; https://doi.org/10.3390/pharmaceutics15092230 - 29 Aug 2023
Cited by 1 | Viewed by 1205
Abstract
Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO2 laser for the manufacturing [...] Read more.
Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO2 laser for the manufacturing of carvedilol personalised dosage forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.125, 6.25, and 12.5 mg. The tuning of the SLS processing laser intensity parameter improved printability and impacted the tablet hardness, friability, CVD dissolution rate, and the total amount of drug released. Physicochemical characterization showed the presence of CVD in the amorphous state. X-ray micro-CT analysis demonstrated that the applied CO2 intensity affected the total tablet porosity, which was reduced with increased laser intensity. The study demonstrated that SLS is a suitable technology for the development of personalised medicines that meet the required specifications and patient needs. Full article
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22 pages, 6187 KiB  
Article
Customizable 3D Printed Implants Containing Triamcinolone Acetonide: Development, Analysis, Modification, and Modeling of Drug Release
by Hanna Ponsar and Julian Quodbach
Pharmaceutics 2023, 15(8), 2097; https://doi.org/10.3390/pharmaceutics15082097 - 08 Aug 2023
Viewed by 830
Abstract
Three-dimensional-printed customizable drug-loaded implants provide promising opportunities to improve the current therapy options. In this study, we present a modular implant in which shape, dosage, and drug release can be individualized independently of each other to patient characteristics to improve parenteral therapy with [...] Read more.
Three-dimensional-printed customizable drug-loaded implants provide promising opportunities to improve the current therapy options. In this study, we present a modular implant in which shape, dosage, and drug release can be individualized independently of each other to patient characteristics to improve parenteral therapy with triamcinolone acetonide (TA) over three months. This study focused on the examination of release modification via fused deposition modeling and subsequent prediction. The filaments for printing consisted of TA, ethyl cellulose, hypromellose, and triethyl citrate. Two-compartment implants were successfully developed, consisting of a shape-adaptable shell and an embedded drug-loaded network. For the network, different strand widths and pore size combinations were printed and analyzed in long-term dissolution studies to evaluate their impact on the release performance. TA release varied between 8.58 ± 1.38 mg and 21.93 mg ± 1.31 mg over three months depending on the network structure and the resulting specific surface area. Two different approaches were employed to predict the TA release over time. Because of the varying release characteristics, applicability was limited, but successful in several cases. Using a simple Higuchi-based approach, good release predictions could be made for a release time of 90 days from the release data of the initial 15 days (RMSEP ≤ 3.15%), reducing the analytical effort and simplifying quality control. These findings are important to establish customizable implants and to optimize the therapy with TA for specific intra-articular diseases. Full article
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28 pages, 5263 KiB  
Article
The Influence of Shape Parameters on Unidirectional Drug Release from 3D Printed Implants and Prediction of Release from Implants with Individualized Shapes
by Vanessa Domsta, Christin Hänsch, Stine Lenz, Ziwen Gao, Farnaz Matin-Mann, Verena Scheper, Thomas Lenarz and Anne Seidlitz
Pharmaceutics 2023, 15(4), 1276; https://doi.org/10.3390/pharmaceutics15041276 - 19 Apr 2023
Cited by 1 | Viewed by 1325
Abstract
The local treatment of diseases by drug-eluting implants is a promising tool to enable successful therapy under potentially reduced systemic side effects. Especially, the highly flexible manufacturing technique of 3D printing provides the opportunity for the individualization of implant shapes adapted to the [...] Read more.
The local treatment of diseases by drug-eluting implants is a promising tool to enable successful therapy under potentially reduced systemic side effects. Especially, the highly flexible manufacturing technique of 3D printing provides the opportunity for the individualization of implant shapes adapted to the patient-specific anatomy. It can be assumed that variations in shape can strongly affect the released amounts of drug per time. This influence was investigated by performing drug release studies with model implants of different dimensions. For this purpose, bilayered model implants in a simplified geometrical shape in form of bilayered hollow cylinders were developed. The drug-loaded abluminal part consisted of a suitable polymer ratio of Eudragit® RS and RL, while the drug-free luminal part composed of polylactic acid served as a diffusion barrier. Implants with different heights and wall thicknesses were produced using an optimized 3D printing process, and drug release was determined in vitro. The area-to-volume ratio was identified as an important parameter influencing the fractional drug release from the implants. Based on the obtained results drug release from 3D printed implants with individual shapes exemplarily adapted to the frontal neo-ostial anatomy of three different patients was predicted and also tested in an independent set of experiments. The similarity of predicted and tested release profiles indicates the predictability of drug release from individualized implants for this particular drug-eluting system and could possibly facilitate the estimation of the performance of customized implants independent of individual in vitro testing of each implant geometry. Full article
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17 pages, 4634 KiB  
Article
Design and Characterization of Carboplatin and Paclitaxel Loaded PCL Filaments for 3D Printed Controlled Release Intrauterine Implants
by Cem Varan, Davut Aksüt, Murat Şen and Erem Bilensoy
Pharmaceutics 2023, 15(4), 1154; https://doi.org/10.3390/pharmaceutics15041154 - 05 Apr 2023
Cited by 2 | Viewed by 1471
Abstract
Uterine cancer is the fourth most common cancer in women. Despite various chemotherapy approaches, the desired effect has not yet been achieved. The main reason is each patient responds differently to standard treatment protocols. The production of personalized drugs and/or drug-loaded implants is [...] Read more.
Uterine cancer is the fourth most common cancer in women. Despite various chemotherapy approaches, the desired effect has not yet been achieved. The main reason is each patient responds differently to standard treatment protocols. The production of personalized drugs and/or drug-loaded implants is not possible in today’s pharmaceutical industry; 3D printers allow for the rapid and flexible preparation of personalized drug-loaded implants. However, the key point is the preparation of drug-loaded working material such as filament for 3D printers. In this study, two different anticancer (paclitaxel, carboplatin) drug-loaded PCL filaments with a 1.75 mm diameter were prepared with a hot-melt extruder. To optimize the filament for a 3D printer, different PCL Mn, cyclodextrins and different formulation parameters were tried, and a series of characterization studies of filaments were conducted. The encapsulation efficiency, drug release profile and in vitro cell culture studies have shown that 85% of loaded drugs retain their effectiveness, provide a controlled release for 10 days and cause a decrease in cell viability of over 60%. In conclusion, it is possible to prepare optimum dual anticancer drug-loaded filaments for FDM 3D printers. Drug-eluting personalized intra-uterine devices can be designed for the treatment of uterine cancer by using these filaments. Full article
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21 pages, 2992 KiB  
Article
3D Printing of Paracetamol Suppositories: An Automated Manufacturing Technique for Individualized Therapy
by Vanessa Domsta, Julius Krause, Werner Weitschies and Anne Seidlitz
Pharmaceutics 2022, 14(12), 2676; https://doi.org/10.3390/pharmaceutics14122676 - 01 Dec 2022
Cited by 5 | Viewed by 3778
Abstract
Pharmaceutical compounding using the molding technique is the currently applied method for the on-demand manufacturing of suppositories and pessaries. Potential errors of this method are difficult to detect, and the possibilities of individualization of size and shape of the suppositories are limited. In [...] Read more.
Pharmaceutical compounding using the molding technique is the currently applied method for the on-demand manufacturing of suppositories and pessaries. Potential errors of this method are difficult to detect, and the possibilities of individualization of size and shape of the suppositories are limited. In this study, a syringe-based semi-solid 3D printing technique was developed for the manufacturing of suppositories in three different printing designs with the suppository bases polyethylene glycol (PEG) and hard fat (HF). The 3D printed suppositories were analyzed for their visual appearance, uniformity of mass and content, diametrical dimension, breaking force and release behavior and compared to suppositories of the same composition prepared by a commonly used molding technique. The results showed no adverse properties for the 3D printed suppositories compared to the molded ones. Moreover, the easy adaptation of shape using the 3D printing technique was demonstrated by the printing of different sizes and infill structures. Thus, 3D printing has great potential to complement the available manufacturing methods for compounded suppositories, as it represents an automated system for the individualized manufacturing of suppositories that meet patients’ needs. Full article
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19 pages, 4041 KiB  
Article
In-House Innovative “Diamond Shaped” 3D Printed Microfluidic Devices for Lysozyme-Loaded Liposomes
by Federica Sommonte, Edward Weaver, Essyrose Mathew, Nunzio Denora and Dimitrios A. Lamprou
Pharmaceutics 2022, 14(11), 2484; https://doi.org/10.3390/pharmaceutics14112484 - 16 Nov 2022
Cited by 14 | Viewed by 1853
Abstract
Nanotechnology applications have emerged as one of the most actively researched areas in recent years. As a result, substantial study into nanoparticulate lipidic systems and liposomes (LPs) has been conducted. Regardless of the advantages, various challenges involving traditional manufacturing processes have hampered their [...] Read more.
Nanotechnology applications have emerged as one of the most actively researched areas in recent years. As a result, substantial study into nanoparticulate lipidic systems and liposomes (LPs) has been conducted. Regardless of the advantages, various challenges involving traditional manufacturing processes have hampered their expansion. Here, the combination of microfluidic technology (MF) and 3D printing (3DP) digital light processing (DLP) was fruitfully investigated in the creation of novel, previously unexplored “diamond shaped” devices suitable for the production of LPs carrying lysozyme as model drug. Computer-aided design (CAD) software was used designing several MF devices with significantly multiple and diverse geometries. These were printed using a high-performance DLP 3DP, resulting in extremely high-resolution chips that were tested to optimize the experimental condition of MF-based LPs. Monodisperse narrow-sized lysozyme-loaded PEGylated LPs were produced using in-house devices. The developed formulations succumbed to stability tests to determine their consistency, and then an encapsulation efficacy (EE) study was performed, yielding good findings. The in vitro release study indicated that lysozyme-loaded LPs could release up to 93% of the encapsulated cargo within 72 h. Therefore, the proficiency of the association between MF and 3DP was demonstrated, revealing a potential growing synergy. Full article
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