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16 pages, 13973 KiB

Open AccessEditor’s ChoiceArticle

3D Printing of Biodegradable Polymeric Microneedles for Transdermal Drug Delivery Applications

by Faisal Khaled Aldawood, Santosh Kumar Parupelli, Abhay Andar and Salil Desai

Pharmaceutics 2024, 16(2), 237; https://doi.org/10.3390/pharmaceutics16020237 - 6 Feb 2024

Cited by 6 | Viewed by 2678

Abstract

Microneedle (MN) technology is an optimal choice for the delivery of drugs via the transdermal route, with a minimally invasive procedure. MN applications are varied from drug delivery, cosmetics, tissue engineering, vaccine delivery, and disease diagnostics. The MN is a biomedical device that [...] Read more.

Microneedle (MN) technology is an optimal choice for the delivery of drugs via the transdermal route, with a minimally invasive procedure. MN applications are varied from drug delivery, cosmetics, tissue engineering, vaccine delivery, and disease diagnostics. The MN is a biomedical device that offers many advantages including but not limited to a painless experience, being time-effective, and real-time sensing. This research implements additive manufacturing (AM) technology to fabricate MN arrays for advanced therapeutic applications. Stereolithography (SLA) was used to fabricate six MN designs with three aspect ratios. The MN array included conical-shaped 100 needles (10 × 10 needle) in each array. The microneedles were characterized using optical and scanning electron microscopy to evaluate the dimensional accuracy. Further, mechanical and insertion tests were performed to analyze the mechanical strength and skin penetration capabilities of the polymeric MN. MNs with higher aspect ratios had higher deformation characteristics suitable for penetration to deeper levels beyond the stratum corneum. MNs with both 0.3 mm and 0.4 mm base diameters displayed consistent force–displacement behavior during a skin-equivalent penetration test. This research establishes guidelines for fabricating polymeric MN for high-accuracy and low-cost 3D printing. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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17 pages, 3489 KiB

Open AccessArticle

Exploring Environmental Settings to Improve the Printability of Paroxetine-Loaded Filaments by Fused Deposition Modelling

by Sara Figueiredo, Ana I. Fernandes, Fátima G. Carvalho and João F. Pinto

Pharmaceutics 2023, 15(11), 2636; https://doi.org/10.3390/pharmaceutics15112636 - 16 Nov 2023

Cited by 2 | Viewed by 1182

Abstract

The successful integration of hot-melt extrusion (HME) and fused deposition modelling (FDM) depends on a better understanding of the impact of environmental conditions on the printability of formulations, since they significantly affect the properties of the raw materials, whose control is crucial to [...] Read more.

The successful integration of hot-melt extrusion (HME) and fused deposition modelling (FDM) depends on a better understanding of the impact of environmental conditions on the printability of formulations, since they significantly affect the properties of the raw materials, whose control is crucial to enable three-dimensional printing (3DP). Hence, the objective of this work was to investigate the correlation between the environmental settings and the properties of paroxetine (PRX)-loaded filaments, previously produced by HME, which affect printability by FDM. The influence of different drying methods of the physical mixtures (PMs) and HME-filaments (FILs) on the quality and printability of these products was also assessed. The printability of FILs was evaluated in terms of the water content, and the mechanical and thermal properties of the products. Stability studies and physicochemical, thermal, and in vitro dissolution tests were carried out on the 3D-printed tablets. Stability studies demonstrated the high ductility of the PRX loaded FILs, especially under high humidity conditions. Under low humidity storage conditions (11% RH), the FILs became stiffer and were successfully used to feed the FDM printer. Water removal was slow when carried out passively in a controlled atmosphere (desiccator) or accelerated by using active drying methods (heat or microwave). Pre-drying of the PRX/excipients and/or PMs did not show any positive effect on the printability of the FIL. On the contrary, dry heat and, preferably, microwave mediated drying processes were shown to reduce the holding time required for successful FDM printing, enabling on-demand production at the point of care. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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23 pages, 5779 KiB

Open AccessEditor’s ChoiceArticle

Development of 3D-Printed Bicompartmental Devices by Dual-Nozzle Fused Deposition Modeling (FDM) for Colon-Specific Drug Delivery

by Fatemeh Shojaie, Carmen Ferrero and Isidoro Caraballo

Pharmaceutics 2023, 15(9), 2362; https://doi.org/10.3390/pharmaceutics15092362 - 21 Sep 2023

Cited by 10 | Viewed by 1833

Abstract

Dual-nozzle fused deposition modeling (FDM) is a 3D printing technique that allows for the simultaneous printing of two polymeric filaments and the design of complex geometries. Hence, hybrid formulations and structurally different sections can be combined into the same dosage form to achieve [...] Read more.

Dual-nozzle fused deposition modeling (FDM) is a 3D printing technique that allows for the simultaneous printing of two polymeric filaments and the design of complex geometries. Hence, hybrid formulations and structurally different sections can be combined into the same dosage form to achieve customized drug release kinetics. The objective of this study was to develop a novel bicompartmental device by dual-nozzle FDM for colon-specific drug delivery. Hydroxypropylmethylcellulose acetate succinate (HPMCAS) and polyvinyl alcohol (PVA) were selected as matrix-forming polymers of the outer pH-dependent and the inner water-soluble compartments, respectively. 5-Aminosalicylic acid (5-ASA) was selected as the model drug. Drug-free HPMCAS and drug-loaded PVA filaments suitable for FDM were extruded, and their properties were assessed by thermal, X-ray diffraction, microscopy, and texture analysis techniques. 5-ASA (20% w/w) remained mostly crystalline in the PVA matrix. Filaments were successfully printed into bicompartmental devices combining an outer cylindrical compartment and an inner spiral-shaped compartment that communicates with the external media through an opening. Scanning electron microscopy and X-ray tomography analysis were performed to guarantee the quality of the 3D-printed devices. In vitro drug release tests demonstrated a pH-responsive biphasic release pattern: a slow and sustained release period (pH values of 1.2 and 6.8) controlled by drug diffusion followed by a faster drug release phase (pH 7.4) governed by polymer relaxation/erosion. Overall, this research demonstrates the feasibility of the dual-nozzle FDM technique to obtain an innovative 3D-printed bicompartmental device for targeting 5-ASA to the colon. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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21 pages, 5860 KiB

Open AccessArticle

Transscleral Delivery of Dexamethasone-Loaded Microparticles Using a Dissolving Microneedle Array

by Rawan Fitaihi, Shorooq Abukhamees, Mine Orlu and Duncan Q. M. Craig

Pharmaceutics 2023, 15(6), 1622; https://doi.org/10.3390/pharmaceutics15061622 - 30 May 2023

Cited by 11 | Viewed by 2276

Abstract

Microneedles (MNs) have attracted considerable interest as a means of ocular drug delivery, a challenging delivery route due to the limitations imposed by the various biological barriers associated with this organ. In this study, a novel ocular drug delivery system was developed by [...] Read more.

Microneedles (MNs) have attracted considerable interest as a means of ocular drug delivery, a challenging delivery route due to the limitations imposed by the various biological barriers associated with this organ. In this study, a novel ocular drug delivery system was developed by formulating a dissolvable MN array containing dexamethasone-loaded PLGA microparticles for scleral drug deposition. The microparticles serve as a drug reservoir for controlled transscleral delivery. The MNs displayed sufficient mechanical strength to penetrate the porcine sclera. Dexamethasone (Dex) scleral permeation was significantly higher than in topically instilled dosage forms. The MN system was able to distribute the drug through the ocular globe, with 19.2% of the administered Dex detected in the vitreous humour. Additionally, images of the sectioned sclera confirmed the diffusion of fluorescent-labelled microparticles within the scleral matrix. The system therefore represents a potential approach for minimally invasive Dex delivery to the posterior of the eye, which lends itself to self-administration and hence high patient convenience. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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23 pages, 7571 KiB

Open AccessArticle

3D-Printed Gastroretentive Tablets Loaded with Niclosamide Nanocrystals by the Melting Solidification Printing Process (MESO-PP)

by Juan Pablo Real, Daniel Andrés Real, Lucía Lopez-Vidal, Bruno Andrés Barrientos, Karen Bolaños, Mariano Guillermo Tinti, Nicolás Javier Litterio, Marcelo Javier Kogan and Santiago Daniel Palma

Pharmaceutics 2023, 15(5), 1387; https://doi.org/10.3390/pharmaceutics15051387 - 30 Apr 2023

Cited by 13 | Viewed by 2864

Abstract

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form [...] Read more.

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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15 pages, 2192 KiB

Open AccessArticle

Development of 3D Printed Multi-Layered Orodispersible Films with Porous Structure Applicable as a Substrate for Inkjet Printing

by Jan Elbl, Martin Veselý, Dagmar Blaháčková, Jaroslav Ondruš, Pavel Kulich, Eliška Mašková, Josef Mašek and Jan Gajdziok

Pharmaceutics 2023, 15(2), 714; https://doi.org/10.3390/pharmaceutics15020714 - 20 Feb 2023

Cited by 6 | Viewed by 2972

Abstract

The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for [...] Read more.

The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl^® 300, Fujisil^®, Syloid^® 244 FP, Syloid^® XDP 3050, Neusilin^® S2, Neusilin^® US2, and Neusilin^® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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19 pages, 5707 KiB

Open AccessArticle

Hybrid Manufacturing of Oral Solid Dosage Forms via Overprinting of Injection-Molded Tablet Substrates

by Han Xu, Farnoosh Ebrahimi, Ke Gong, Zhi Cao, Evert Fuenmayor and Ian Major

Pharmaceutics 2023, 15(2), 507; https://doi.org/10.3390/pharmaceutics15020507 - 3 Feb 2023

Cited by 8 | Viewed by 2921

Abstract

Since 3D printing allows for patient-specific dosage forms, it has become a major focus in pharmaceutical research. However, it is difficult to scale up drug product manufacturing. Injection molding has been used in conjunction with hot-melt extrusion to mass produce drug products, but [...] Read more.

Since 3D printing allows for patient-specific dosage forms, it has become a major focus in pharmaceutical research. However, it is difficult to scale up drug product manufacturing. Injection molding has been used in conjunction with hot-melt extrusion to mass produce drug products, but making tailored solid dosage forms with this technology is neither cost-effective nor simple. This study explored the use of a combination of fused filament fabrication and injection molding to create patient-specific solid dosage forms. A tablet fixation and location template was used to overprint directly on injection-molded tablet bases, and theophylline was combined with polycaprolactone and Kollidon^® VA64 via hot-melt extrusion to produce the filament. Dynamic mechanical analysis was used to evaluate the brittleness of the filament, and differential scanning calorimetry was used to analyze the thermal results. The results showed that theophylline had a flow promoting effect on the polymer blend and that overprinted tablets were manufactured faster than 3D-printed tablets. Drug release studies also showed that overprinted tablets released faster than injection-molded tablets. This method demonstrates the potential of hybrid manufacturing for the pharmaceutical industry as a means of bridging the gap between personalized dosage forms and mass production. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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13 pages, 2835 KiB

Open AccessArticle

Evaluation of a Medical Grade Thermoplastic Polyurethane for the Manufacture of an Implantable Medical Device: The Impact of FDM 3D-Printing and Gamma Sterilization

by Marie-Stella M’Bengue, Thomas Mesnard, Feng Chai, Mickaël Maton, Valérie Gaucher, Nicolas Tabary, Maria-José García-Fernandez, Jonathan Sobocinski, Bernard Martel and Nicolas Blanchemain

Pharmaceutics 2023, 15(2), 456; https://doi.org/10.3390/pharmaceutics15020456 - 30 Jan 2023

Cited by 14 | Viewed by 4172

Abstract

Three-dimensional printing (3DP) of thermoplastic polyurethane (TPU) is gaining interest in the medical industry thanks to the combination of tunable properties that TPU exhibits and the possibilities that 3DP processes offer concerning precision, time, and cost of fabrication. We investigated the implementation of [...] Read more.

Three-dimensional printing (3DP) of thermoplastic polyurethane (TPU) is gaining interest in the medical industry thanks to the combination of tunable properties that TPU exhibits and the possibilities that 3DP processes offer concerning precision, time, and cost of fabrication. We investigated the implementation of a medical grade TPU by fused deposition modelling (FDM) for the manufacturing of an implantable medical device from the raw pellets to the gamma (γ) sterilized 3DP constructs. To the authors’ knowledge, there is no such guide/study implicating TPU, FDM 3D-printing and gamma sterilization. Thermal properties analyzed by differential scanning calorimetry (DSC) and molecular weights measured by size exclusion chromatography (SEC) were used as monitoring indicators through the fabrication process. After gamma sterilization, surface chemistry was assessed by water contact angle (WCA) measurement and infrared spectroscopy (ATR-FTIR). Mechanical properties were investigated by tensile testing. Biocompatibility was assessed by means of cytotoxicity (ISO 10993-5) and hemocompatibility assays (ISO 10993-4). Results showed that TPU underwent degradation through the fabrication process as both the number-averaged (Mn) and weight-averaged (Mw) molecular weights decreased (7% Mn loss, 30% Mw loss, p < 0.05). After gamma sterilization, Mw increased by 8% (p < 0.05) indicating that crosslinking may have occurred. However, tensile properties were not impacted by irradiation. Cytotoxicity (ISO 10993-5) and hemocompatibility (ISO 10993-4) assessments after sterilization showed vitality of cells (132% ± 3%, p < 0.05) and no red blood cell lysis. We concluded that gamma sterilization does not highly impact TPU regarding our application. Our study demonstrates the processability of TPU by FDM followed by gamma sterilization and can be used as a guide for the preliminary evaluation of a polymeric raw material in the manufacturing of a blood contacting implantable medical device. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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16 pages, 3575 KiB

Open AccessArticle

Fabrication of Gastro-Floating Famotidine Tablets: Hydroxypropyl Methylcellulose-Based Semisolid Extrusion 3D Printing

by Hyun Seok Yang and Dong Wuk Kim

Pharmaceutics 2023, 15(2), 316; https://doi.org/10.3390/pharmaceutics15020316 - 18 Jan 2023

Cited by 16 | Viewed by 2778

Abstract

Semisolid extrusion (SSE) three-dimensional (3D) printing uses drug-loaded paste for the printing process, which is capable of constructing intricate 3D structures. This research presents a unique method for fabricating gastro-floating tablets (GFT) using SSE. Paste-loaded famotidine with a matrix made of hydroxypropyl methylcellulose [...] Read more.

Semisolid extrusion (SSE) three-dimensional (3D) printing uses drug-loaded paste for the printing process, which is capable of constructing intricate 3D structures. This research presents a unique method for fabricating gastro-floating tablets (GFT) using SSE. Paste-loaded famotidine with a matrix made of hydroxypropyl methylcellulose (HPMC) were prepared. Nine 3D printed tablets were developed with different HPMC concentrations and infill percentages and evaluated to determine their physicochemical properties, content uniformity, dissolution, and floating duration. The crystallinity of the drug remained unchanged throughout the process. Dissolution profiles demonstrated the correlation between the HPMC concentration/infill percentage and drug release behavior over 10 h. All the fabricated GFTs could float for 10 h and the Korsmeyer-Peppas model described the dissolution kinetics as combination of non-Fickian or anomalous transport mechanisms. The results of this study provided insight into the predictability of SSE 3D printability, which uses hydro-alcoholic gel-API blend materials for GFTs by controlling traditional pharmaceutical excipients and infill percentages. SSE 3D printing could be an effective blueprint for producing controlled-release GFTs, with the additional benefits of simplicity and versatility over conventional methods. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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15 pages, 2425 KiB

Open AccessArticle

Hybrid 3D Printed and Electrospun Multi-Scale Hierarchical Polycaprolactone Scaffolds to Induce Bone Differentiation

by Ainhoa Gonzalez-Pujana, Teresa Carranza, Edorta Santos-Vizcaino, Manoli Igartua, Pedro Guerrero, Rosa Maria Hernandez and Koro de la Caba

Pharmaceutics 2022, 14(12), 2843; https://doi.org/10.3390/pharmaceutics14122843 - 19 Dec 2022

Cited by 7 | Viewed by 2885

Abstract

Complex scaffolds composed of micro- and nano-structures are a key target in tissue engineering and the combination of sequential 3D printing and electrospinning enables the fabrication of these multi-scale structures. In this work, dual 3D printed and electrospun polycaprolactone (PCL) scaffolds with multiple [...] Read more.

Complex scaffolds composed of micro- and nano-structures are a key target in tissue engineering and the combination of sequential 3D printing and electrospinning enables the fabrication of these multi-scale structures. In this work, dual 3D printed and electrospun polycaprolactone (PCL) scaffolds with multiple mesh layers were successfully prepared. The scaffold macro- and micro-porosity were assessed by optical and scanning electron microscopy, showing that electrospun fibers formed aligned meshes within the pores of the scaffold. Consequently, the hydrophilicity of the scaffold increased with time, enhancing cell adhesion and growth. Additionally, compression tests in back and forth cycles demonstrated a good shape recovery behavior of the scaffolds. Biological results indicated that hybrid PCL scaffolds are biocompatible and enable a correct cell culture over time. Moreover, MC3T3-E1 preosteoblast culture on the scaffolds promoted the mineralization, increased the alkaline phosphatase (ALP) activity and upregulated the expression of early and late osteogenic markers, namely ALP and osteopontin (OPN), respectively. These results demonstrate that the sequential combination of 3D printing and electrospinning provides a facile method of incorporating fibers within a 3D printed scaffold, becoming a promising approach towards multi-scale hierarchical scaffolds capable of guiding the osteogenic differentiation. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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18 pages, 2798 KiB

Open AccessArticle

Dose Titration of Solid Dosage Forms via FDM 3D-Printed Mini-Tablets

by Guluzar Gorkem Buyukgoz, Christopher G. Kossor, Shen Ji, Murat Guvendiren and Rajesh N. Davé

Pharmaceutics 2022, 14(11), 2305; https://doi.org/10.3390/pharmaceutics14112305 - 27 Oct 2022

Cited by 4 | Viewed by 2240

Abstract

The robustness of 3D-printed mini-tablets as a platform to administer milligram dosages, intended for age-specific therapy, without the need of tablet splitting while maintaining similar release profiles, was investigated. Griseofulvin, as a model poorly water-soluble drug, and hydroxypropyl cellulose along with Kollicoat Protect [...] Read more.

The robustness of 3D-printed mini-tablets as a platform to administer milligram dosages, intended for age-specific therapy, without the need of tablet splitting while maintaining similar release profiles, was investigated. Griseofulvin, as a model poorly water-soluble drug, and hydroxypropyl cellulose along with Kollicoat Protect as polymers were used to prepare filaments at 1–20% drug concentrations via hot-melt extrusion (HME). Higher drug concentrations served for testing the feasibility of a reduced number of mini-tablets to be administered. A reliable dose titration in the range 0.19–3.91 mg at a high accuracy (R² of 0.999) was achieved through composite unit (multi-unit) mini-tablets. All mini-tablets produced had excellent content uniformity and their label claim values were within the acceptable range, proving that HME processing followed by 3D printing promotes content uniformity even for mini-tablets containing low drug doses (0.19 mg). Remarkably, the proposed approach allowed achieving similar drug release profiles via composite unit mini-tablets as well as single mini-tablets at high drug concentrations. In contrast, split tablets demonstrated different release behaviors, attributed to their size and shape differences. Overall, the distinct advantages of mini-tablets to provide dose flexibility while maintaining similar release profiles was demonstrated. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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17 pages, 2544 KiB

Open AccessArticle

Tunable Drug Release from Fused Deposition Modelling (FDM) 3D-Printed Tablets Fabricated Using a Novel Extrudable Polymer

by Vishvesh Raje, Siddhant Palekar, Sabrina Banella and Ketan Patel

Pharmaceutics 2022, 14(10), 2192; https://doi.org/10.3390/pharmaceutics14102192 - 14 Oct 2022

Cited by 12 | Viewed by 2843

Abstract

Three-dimensional (3D) printing is proving to be a pivotal technology for developing personalized dosage forms with bench to bedside feasibility. Fused deposition modelling (FDM) 3D printing has emerged as the most used technique wherein molten drug-loaded polymer filaments are deposited layer-by-layer to fabricate [...] Read more.

Three-dimensional (3D) printing is proving to be a pivotal technology for developing personalized dosage forms with bench to bedside feasibility. Fused deposition modelling (FDM) 3D printing has emerged as the most used technique wherein molten drug-loaded polymer filaments are deposited layer-by-layer to fabricate a predefined shape and internal geometry. However, for precise FDM 3D printing, it is imperative for the filaments to have peculiar mechanical/physicochemical properties, which the majority of the FDA/GRAS approved polymers lack. In the current study, a novel water-soluble polymer, Poly(2-ethyl-tetra-oxazoline) [PETOx] has been investigated as an extrudable and printable polymer with two different types of drug molecule—dextromethorphan hydrobromide (DXM) and hydrochlorothiazide (HCTZ). Hot-stage microscopy experiments of drug:polymer (1:1 w/w) and filaments were carried out at 25–275 °C. HCTZ-loaded filament showed higher toughness of 17 ± 3.25 × 10⁶ J/m³ compared with DXM and drug-free filament. Moisture sorption and flexural analysis was performed to understand the correlation of mechanical properties and storage humidity to printability. Varying the number of outer perimeters of each layer (shell number) was observed to affect the drug release pattern from the printlets. The DXM one-shell printlet showed >80%, whereas the DXM five-shell printlet showed >60% of the drug release within 60 min. PETOx could prove to be a high-performance and versatile 3D printable polymer. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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11 pages, 5306 KiB

Open AccessArticle

Fabrication of Mucoadhesive Films Containing Pharmaceutical Ionic Liquid and Eudragit Polymer Using Pressure-Assisted Microsyringe-Type 3D Printer for Treating Oral Mucositis

by Tatsuaki Tagami, Maya Okamura, Koki Ogawa and Tetsuya Ozeki

Pharmaceutics 2022, 14(9), 1930; https://doi.org/10.3390/pharmaceutics14091930 - 13 Sep 2022

Cited by 11 | Viewed by 2816

Abstract

Oral mucositis in the oral cavity, caused by radiation therapy and chemotherapy, requires personalized care and therapy due to variations in the lesions of patients. In the present study, we fabricated a model of personalized oral film containing an ibuprofen/lidocaine ionic liquid (IL) [...] Read more.

Oral mucositis in the oral cavity, caused by radiation therapy and chemotherapy, requires personalized care and therapy due to variations in the lesions of patients. In the present study, we fabricated a model of personalized oral film containing an ibuprofen/lidocaine ionic liquid (IL) for patients with oral mucositis using a pressure-assisted microsyringe-type 3D printer at room temperature. The film contained a Eudragit polymer (L100, EPO, or RSPO) to make the film solid, and the printer ink was composed of organo ink (organic solvent to dissolve both drugs and the Eudragit polymer). The viscosity of the printer ink was assessed to investigate its extrudability. The contact angle and the surface tension at the interface between each liquid printer ink and a solid polypropylene sheet were measured to determine the retention of the ink in 3D printing. The physical properties of IL-loaded Eudragit-based dry films were examined by X-ray diffraction and differential scanning calorimetry. Dissolution tests indicated that IL-loaded films containing a Eudragit polymer exhibited different drug release rates in phosphate buffer (pH 6.8; Eudragit L100 > IL alone > Eudragit EPO > Eudragit RSPO). These results provide useful information for the specific fabrication of IL-loaded polymer-based films using organo inks and pressure-assisted microsyringe-type 3D printers. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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16 pages, 43668 KiB

Open AccessArticle

Three-Dimensional Printing of an Apigenin-Loaded Mucoadhesive Film for Tailored Therapy to Oral Leukoplakia and the Chemopreventive Effect on a Rat Model of Oral Carcinogenesis

by Hiroyuki Takashima, Tatsuaki Tagami, Shinichiro Kato, Heeju Pae, Tetsuya Ozeki and Yasuyuki Shibuya

Pharmaceutics 2022, 14(8), 1575; https://doi.org/10.3390/pharmaceutics14081575 - 28 Jul 2022

Cited by 10 | Viewed by 2440

Abstract

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient’s quality of life. In the present study, we focused on the flavonoid [...] Read more.

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient’s quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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21 pages, 45400 KiB

Open AccessEditor’s ChoiceArticle

Influence of the Binder Jetting Process Parameters and Binder Liquid Composition on the Relevant Attributes of 3D-Printed Tablets

by Klemen Kreft, Zoran Lavrič, Tijana Stanić, Petra Perhavec and Rok Dreu

Pharmaceutics 2022, 14(8), 1568; https://doi.org/10.3390/pharmaceutics14081568 - 28 Jul 2022

Cited by 15 | Viewed by 3890

Abstract

Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties [...] Read more.

Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties of tablets. A model formulation containing the ketoprofen drug was developed and used as a base for optimization. Firstly, important printing parameters were identified with a fractional factorial design. Saturation and layer height critically influenced selected tablet properties. Relevant process parameters were optimized for tablet mechanical strength by using the D-optimization DoE approach. The best mechanical properties were achieved when saturation was set to 1 and layer height to 150 µm. On the other hand, binder ink composition did not appear to impact tablet mechanical strength as much as process parameters did. Three ethanol-water mixtures were tested at three tablet strength levels and no definitive conclusions could be drawn. The binder jetting process can be wasteful, especially if the unbound powder cannot be reused. To determine the suitability of powder blend recycling, the ketoprofen content was measured for 27 subsequent batches of tablets. While the trendline did indicate a slight reduction in ketoprofen content, the powder blend reuse can nevertheless be employed. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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Review

Jump to: Research

34 pages, 2211 KiB

Open AccessReview

Excipients in Pharmaceutical Additive Manufacturing: A Comprehensive Exploration of Polymeric Material Selection for Enhanced 3D Printing

by Christian Muehlenfeld, Patrick Duffy, Fengyuan Yang, David Zermeño Pérez, Firas El-Saleh and Thomas Durig

Pharmaceutics 2024, 16(3), 317; https://doi.org/10.3390/pharmaceutics16030317 - 24 Feb 2024

Cited by 2 | Viewed by 2355

Abstract

This review provides a comprehensive overview of additive manufacturing (AM) or 3D-printing (3DP) applications in the pharmaceutical industry, with a particular focus on the critical role of polymer selection. By providing insights into how material properties influence the 3DP process and the quality [...] Read more.

This review provides a comprehensive overview of additive manufacturing (AM) or 3D-printing (3DP) applications in the pharmaceutical industry, with a particular focus on the critical role of polymer selection. By providing insights into how material properties influence the 3DP process and the quality of the final product, this review aims to contribute to a better understanding of the interplay between polymers and pharmaceutical 3DP. As 3DP technologies are increasingly integrated into pharmaceutical sciences, this review contributes insights into the nuanced process of polymer selection, serving mainly as a foundational guide for researchers and formulators new to the subject seeking to harness the full potential of pharmaceutical 3DP by understanding the physicochemical properties, roles, and functions of used polymers in 3D-printed dosage forms and medical devices. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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Open AccessReview

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals

by Dolores R. Serrano, Aytug Kara, Iván Yuste, Francis C. Luciano, Baris Ongoren, Brayan J. Anaya, Gracia Molina, Laura Diez, Bianca I. Ramirez, Irving O. Ramirez, Sergio A. Sánchez-Guirales, Raquel Fernández-García, Liliana Bautista, Helga K. Ruiz and Aikaterini Lalatsa

Pharmaceutics 2023, 15(2), 313; https://doi.org/10.3390/pharmaceutics15020313 - 17 Jan 2023

Cited by 61 | Viewed by 10999

Abstract

3D printing technologies enable medicine customization adapted to patients’ needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a [...] Read more.

3D printing technologies enable medicine customization adapted to patients’ needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing (“nanoprinting”) brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice. Full article

(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)

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