Editorial

3 pages, 202 KiB

Open AccessEditorial

Special Issue for “3D Printing of Drug Formulations”

by Touraj Ehtezazi

Pharmaceuticals 2023, 16(10), 1372; https://doi.org/10.3390/ph16101372 - 28 Sep 2023

Viewed by 624

Three-dimensional printing (3DP) is rapidly innovating the manufacturing process and provides opportunities that have never been seen before [...] Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

Research

Jump to: Editorial, Review

14 pages, 5637 KiB

Open AccessArticle

Fabrication and Characterization of Oxygen-Generating Polylactic Acid/Calcium Peroxide Composite Filaments for Bone Scaffolds

by Abdullah Mohammed, Abdu Saeed, Amr Elshaer, Ammar A. Melaibari, Adnan Memić, Hany Hassanin and Khamis Essa

Pharmaceuticals 2023, 16(4), 627; https://doi.org/10.3390/ph16040627 - 20 Apr 2023

Cited by 3 | Viewed by 1847

Abstract

The latest advancements in bone scaffold technology have introduced novel biomaterials that have the ability to generate oxygen when implanted, improving cell viability and tissue maturation. In this paper, we present a new oxygen-generating polylactic acid (PLA)/calcium peroxide (CPO) composite filament that can [...] Read more.

The latest advancements in bone scaffold technology have introduced novel biomaterials that have the ability to generate oxygen when implanted, improving cell viability and tissue maturation. In this paper, we present a new oxygen-generating polylactic acid (PLA)/calcium peroxide (CPO) composite filament that can be used in 3D printing scaffolds. The composite material was prepared using a wet solution mixing method, followed by drying and hot melting extrusion. The concentration of calcium peroxide in the composite varied from 0% to 9%. The prepared filaments were characterized in terms of the presence of calcium peroxide, the generated oxygen release, porosity, and antibacterial activities. Data obtained from scanning electron microscopy and X-ray diffraction showed that the calcium peroxide remained stable in the composite. The maximum calcium and oxygen release was observed in filaments with a 6% calcium peroxide content. In addition, bacterial inhibition was achieved in samples with a calcium peroxide content of 6% or higher. These results indicate that an optimized PLA filament with a 6% calcium peroxide content holds great promise for improving bone generation through bone cell oxygenation and resistance to bacterial infections. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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20 pages, 4017 KiB

Open AccessArticle

Personalised 3D-Printed Mucoadhesive Gastroretentive Hydrophilic Matrices for Managing Overactive Bladder (OAB)

by Zara Khizer, Muhammad R. Akram, Muhammad Azam Tahir, Weidong Liu, Shan Lou, Barbara R. Conway and Muhammad Usman Ghori

Pharmaceuticals 2023, 16(3), 372; https://doi.org/10.3390/ph16030372 - 28 Feb 2023

Cited by 3 | Viewed by 2091

Abstract

Overactive bladder (OAB) is a symptomatic complex condition characterised by frequent urinary urgency, nocturia, and urinary incontinence with or without urgency. Gabapentin is an effective treatment for OAB, but its narrow absorption window is a concern, as it is preferentially absorbed from the [...] Read more.

Overactive bladder (OAB) is a symptomatic complex condition characterised by frequent urinary urgency, nocturia, and urinary incontinence with or without urgency. Gabapentin is an effective treatment for OAB, but its narrow absorption window is a concern, as it is preferentially absorbed from the upper small intestine, resulting in poor bioavailability. We aimed to develop an extended release, intragastric floating system to overcome this drawback. For this purpose, plasticiser-free filaments of PEO (polyethylene oxide) and the drug (gabapentin) were developed using hot melt extrusion. The filaments were extruded successfully with 98% drug loading, possessed good mechanical properties, and successfully produced printed tablets using fused deposition modelling (FDM). Tablets were printed with varying shell numbers and infill density to investigate their floating capacity. Among the seven matrix tablet formulations, F2 (2 shells, 0% infill) showed the highest floating time, i.e., more than 10 h. The drug release rates fell as the infill density and shell number increased. However, F2 was the best performing formulation in terms of floating and release and was chosen for in vivo (pharmacokinetic) studies. The pharmacokinetic findings exhibit improved gabapentin absorption compared to the control (oral solution). Overall, it can be concluded that 3D printing technology is an easy-to-use approach which demonstrated its benefits in developing medicines based on a mucoadhesive gastroretentive strategy, improving the absorption of gabapentin with potential for the improved management of OAB. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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16 pages, 2625 KiB

Open AccessArticle

Multifunctional Three-Dimensional Printed Copper Loaded Calcium Phosphate Scaffolds for Bone Regeneration

by Amit Pillai, Jaidev Chakka, Niloofar Heshmathi, Yu Zhang, Faez Alkadi and Mohammed Maniruzzaman

Pharmaceuticals 2023, 16(3), 352; https://doi.org/10.3390/ph16030352 - 25 Feb 2023

Cited by 2 | Viewed by 2097

Abstract

Bone regeneration using inorganic nanoparticles is a robust and safe approach. In this paper, copper nanoparticles (Cu NPs) loaded with calcium phosphate scaffolds were studied for their bone regeneration potential in vitro. The pneumatic extrusion method of 3D printing was employed to prepare [...] Read more.

Bone regeneration using inorganic nanoparticles is a robust and safe approach. In this paper, copper nanoparticles (Cu NPs) loaded with calcium phosphate scaffolds were studied for their bone regeneration potential in vitro. The pneumatic extrusion method of 3D printing was employed to prepare calcium phosphate cement (CPC) and copper loaded CPC scaffolds with varying wt% of copper nanoparticles. A new aliphatic compound Kollisolv MCT 70 was used to ensure the uniform mixing of copper nanoparticles with CPC matrix. The printed scaffolds were studied for physico-chemical characterization for surface morphology, pore size, wettability, XRD, and FTIR. The copper ion release was studied in phosphate buffer saline at pH 7.4. The in vitro cell culture studies for the scaffolds were performed using human mesenchymal stem cells (hMSCs). The cell proliferation study in CPC-Cu scaffolds showed significant cell growth compared to CPC. The CPC-Cu scaffolds showed improved alkaline phosphatase activity and angiogenic potential compared to CPC. The CPC-Cu scaffolds showed significant concentration dependent antibacterial activity in Staphylococcus aureus. Overall, the CPC scaffolds loaded with 1 wt% Cu NPs showed improved activity compared to other CPC-Cu and CPC scaffolds. The results showed that copper has improved the osteogenic, angiogenic and antibacterial properties of CPC scaffolds, facilitating better bone regeneration in vitro. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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23 pages, 4355 KiB

Open AccessArticle

3D-Printing of Capsule Devices as Compartmentalization Tools for Supported Reagents in the Search of Antiproliferative Isatins

by Camilla Malatini, Carlos Carbajales, Mariángel Luna, Osvaldo Beltrán, Manuel Amorín, Christian F. Masaguer, José M. Blanco, Silvia Barbosa, Pablo Taboada and Alberto Coelho

Pharmaceuticals 2023, 16(2), 310; https://doi.org/10.3390/ph16020310 - 16 Feb 2023

Cited by 1 | Viewed by 1971

Abstract

The application of high throughput synthesis methodologies in the generation of active pharmaceutical ingredients (APIs) currently requires the use of automated and easily scalable systems, easy dispensing of supported reagents in solution phase organic synthesis (SPOS), and elimination of purification and extraction steps. [...] Read more.

The application of high throughput synthesis methodologies in the generation of active pharmaceutical ingredients (APIs) currently requires the use of automated and easily scalable systems, easy dispensing of supported reagents in solution phase organic synthesis (SPOS), and elimination of purification and extraction steps. The recyclability and recoverability of supported reagents and/or catalysts in a rapid and individualized manner is a challenge in the pharmaceutical industry. This objective can be achieved through a suitable compartmentalization of these pulverulent reagents in suitable devices for it. This work deals with the use of customized polypropylene permeable-capsule devices manufactured by 3D printing, using the fused deposition modeling (FDM) technique, adaptable to any type of flask or reactor. The capsules fabricated in this work were easily loaded “in one step” with polymeric reagents for use as scavengers of isocyanides in the work-up process of Ugi multicomponent reactions or as compartmentalized and reusable catalysts in copper-catalyzed cycloadditions (CuAAC) or Heck palladium catalyzed cross-coupling reactions (PCCCRs). The reaction products are different series of diversely substituted isatins, which were tested in cancerous cervical HeLa and murine 3T3 Balb fibroblast cells, obtaining potent antiproliferative activity. This work demonstrates the applicability of 3D printing in chemical processes to obtain anticancer APIs. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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27 pages, 5818 KiB

Open AccessArticle

In Vitro/In Vivo Evaluation of Clomipramine Orodispersible Tablets for the Treatment of Depression and Obsessive-Compulsive Disorder

by Shazia Akram Ghumman, Huma Hameed, Sobia Noreen, Sami A. Al-Hussain, Rizwana Kausar, Ali Irfan, Ramla Shabbir, Maria Rana, Amina Amanat and Magdi E. A. Zaki

Pharmaceuticals 2023, 16(2), 265; https://doi.org/10.3390/ph16020265 - 09 Feb 2023

Cited by 4 | Viewed by 1827

Abstract

The first and only antidepressant drug on the market with solid proof of clinically significant serotonin and noradrenaline reuptake inhibition is clomipramine (CLP). However, significant first-pass metabolism reduces its absorption to less than 62%. It is heavily protein-bound and broadly dispersed across the [...] Read more.

The first and only antidepressant drug on the market with solid proof of clinically significant serotonin and noradrenaline reuptake inhibition is clomipramine (CLP). However, significant first-pass metabolism reduces its absorption to less than 62%. It is heavily protein-bound and broadly dispersed across the body (9–25 L/kg volume of distribution). The purpose of this research was to formulate CLP orodispersible tablets that immediately enable the drug to enter the bloodstream and bypass systemic portal circulation to improve its bioavailability. A factorial design was employed using varied amounts of Plantago ovata mucilage (POM) as a natural superdisintegrant, as well as croscarmellose sodium and crospovidone as synthetic disintegrants. Their physiochemical compatibility was evaluated by FTIR, DSC/TGA, and PXRD analysis. The blend of all formulations was assessed for pre- and post-compaction parameters. The study found that tablets comprising Plantago ovata mucilage as a superdisintegrant showed a rapid in vitro disintegration time, i.e., around 8.39 s, and had an excellent dissolution profile. The anti-depressant efficacy was evaluated by an open-field test (OFT) and the forced swimming test (FST) was applied to create hopelessness and despair behavior as a model of depression in animals (Albino rats). The in vivo study revealed that the efficiency of the optimized formulation (F9) in the treatment of depression is more than the marketed available clomfranil tablet, and may be linked to its rapid disintegration and bypassing of systemic portal circulation. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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23 pages, 9289 KiB

Open AccessArticle

The Use of Micro-Ribbons and Micro-Fibres in the Formulation of 3D Printed Fast Dissolving Oral Films

by Marwan Algellay, Matthew Roberts, Lucy Bosworth, Satyajit D. Sarker, Amos A. Fatokun and Touraj Ehtezazi

Pharmaceuticals 2023, 16(1), 79; https://doi.org/10.3390/ph16010079 - 05 Jan 2023

Cited by 3 | Viewed by 1616

Abstract

Three-dimensional printing (3DP) allows production of novel fast dissolving oral films (FDFs). However, mechanical properties of the films may not be desirable when certain excipients are used. This work investigated whether adding chitosan micro-ribbons or cellulose microfibres will achieve desired FDFs by fused [...] Read more.

Three-dimensional printing (3DP) allows production of novel fast dissolving oral films (FDFs). However, mechanical properties of the films may not be desirable when certain excipients are used. This work investigated whether adding chitosan micro-ribbons or cellulose microfibres will achieve desired FDFs by fused deposition modelling 3DP. Filaments containing polyvinyl alcohol (PVA) and paracetamol as model drug were manufactured at 170 °C. At 130 °C, filaments containing polyvinylpyrrolidone (PVP) and paracetamol were also created. FDFs were printed with plain or mesh patterns at temperatures of 200 °C (PVA) or 180 °C (PVP). Both chitosan micro-ribbons and cellulose micro-fibres improved filament mechanical properties at 1% w/w concentration in terms of flexibility and stiffness. The filaments were not suitable for printing at higher concentrations of chitosan micro-ribbons and cellulose micro-fibres. Furthermore, mesh FDFs containing only 1% chitosan micro-ribbons disintegrated in distilled water within 40.33 ± 4.64 s, while mesh FDFs containing only 7% croscarmellose disintegrated in 55.33 ± 2.86 s, and croscarmellose containing films showed signs of excipient scorching for PVA polymer. Cellulose micro-fibres delayed disintegration of PVA mesh films to 108.66 ± 3.68 s at 1% w/w. In conclusion, only chitosan micro-ribbons created a network of hydrophilic channels within the films, which allowed faster disintegration time at considerably lower concentrations. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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16 pages, 6008 KiB

Open AccessArticle

Investigation of Patient-Centric 3D-Printed Orodispersible Films Containing Amorphous Aripiprazole

by Ju-Hyun Lee, Chulhun Park, In-OK Song, Beom-Jin Lee, Chin-Yang Kang and Jun-Bom Park

Pharmaceuticals 2022, 15(7), 895; https://doi.org/10.3390/ph15070895 - 19 Jul 2022

Cited by 13 | Viewed by 2253

Abstract

The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole (ARP), prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion (HME) filament. Klucel^® LF (hydroxypropyl [...] Read more.

The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole (ARP), prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion (HME) filament. Klucel^® LF (hydroxypropyl cellulose, HPC) and PE-05JPS^® (polyvinyl alcohol, PVA) were used as backbone polymers for 3D printing and solvent casting. HPC-, PVA-, and ARP-loaded filaments were applied for 3D printing using HME. The physicochemical and mechanical properties of the 3D printing filaments and films were optimized based on the composition of the polymers and the processing parameters. The crystalline states of drug and drug-loaded formulations were investigated using differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). The dissolution and disintegration of the 3D-printed films were faster than those of solvent-cast films. HPC-3D printed film was fully disintegrated within 45 ± 3.5 s. The dissolution rate of HPC films reached 80% within 30 min at pH 1.2 and pH 4.0 USP buffer. There was a difference in the dissolution rate of about 5 to 10% compared to PVA films at the same sampling time. The root mean square of the roughness (Rq) values of each sample were evaluated using atomic force microscopy. The higher the Rq value, the rougher the surface, and the larger the surface area, the more salivary fluid penetrated the film, resulting in faster drug release and disintegration. Specifically, The HPC 3D-printed film showed the highest Rq value (102.868 nm) and average surface roughness (85.007 nm). The puncture strength of 3D-printed films had desirable strength with HPC (0.65 ± 0.27 N/mm²) and PVA (0.93 ± 0.15 N/mm²) to prevent deformation compared to those of marketed film products (over 0.34 N/mm²). In conclusion, combining polymer selection and 3D printing technology could innovatively design ODFs composed of ARP to solve the unmet medical needs of psychiatric patients. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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15 pages, 2983 KiB

Open AccessArticle

Development of Advanced 3D-Printed Solid Dosage Pediatric Formulations for HIV Treatment

by Azizah M. Malebari, Aytug Kara, Ahdab N. Khayyat, Khadijah A. Mohammad and Dolores R. Serrano

Pharmaceuticals 2022, 15(4), 435; https://doi.org/10.3390/ph15040435 - 31 Mar 2022

Cited by 16 | Viewed by 2512

Abstract

The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In [...] Read more.

The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children’s needs. This work has demonstrated, for the first time, the feasibility of using direct powder extrusion 3D printing to manufacture personalized pediatric HIV dosage forms based on 6 mm spherical tablets. H-bonding between drugs and excipients (hydroxypropyl methylcellulose and polyethylene glycol) resulted in the formation of amorphous solid dispersions with a zero-order sustained release profile, opposite to the commercially available formulation Kaletra, which exhibited marked drug precipitation at the intestinal pH. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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21 pages, 4831 KiB

Open AccessArticle

Fused Deposition Modeling as a Possible Approach for the Preparation of Orodispersible Tablets

by Thao Tranová, Jolanta Pyteraf, Mateusz Kurek, Witold Jamróz, Witold Brniak, Dita Spálovská, Jan Loskot, Karolina Jurkiewicz, Joanna Grelska, Daniel Kramarczyk, Jitka Mužíková, Marian Paluch and Renata Jachowicz

Pharmaceuticals 2022, 15(1), 69; https://doi.org/10.3390/ph15010069 - 05 Jan 2022

Cited by 10 | Viewed by 2742

Abstract

Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, [...] Read more.

Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, the influence of excipients, and storage conditions on the disintegration time of tablets printed using the fused deposition modeling method. As model pharmaceutical active ingredients (APIs), we used paracetamol and domperidone, characterized by different thermal properties, classified into the various Biopharmaceutical Classification System groups. We found that the high surface/mass ratio of the designed tablet shapes together with the addition of mannitol and controlled humidity storage conditions turned out to be crucial for fast tablet’s disintegration. As a result, mean disintegration time was reduced from 5 min 46 s to 2 min 22 s, and from 11 min 43 s to 2 min 25 s for paracetamol- and domperidone-loaded tablets, respectively, fulfilling the European Pharmacopeia requirement for orodispersible tablets (ODTs). The tablet’s immediate release characteristics were confirmed during the dissolution study: over 80% of APIs were released from printlets within 15 min. Thus, this study proved the possibility of using fused deposition modeling for the preparation of ODTs. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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Review

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25 pages, 5676 KiB

Open AccessReview

4D Printing of Hydrogels: Innovation in Material Design and Emerging Smart Systems for Drug Delivery

by Tuan Sang Tran, Rajkamal Balu, Srinivas Mettu, Namita Roy Choudhury and Naba Kumar Dutta

Pharmaceuticals 2022, 15(10), 1282; https://doi.org/10.3390/ph15101282 - 19 Oct 2022

Cited by 18 | Viewed by 3929

Abstract

Advancements in the material design of smart hydrogels have transformed the way therapeutic agents are encapsulated and released in biological environments. On the other hand, the expeditious development of 3D printing technologies has revolutionized the fabrication of hydrogel systems for biomedical applications. By [...] Read more.

Advancements in the material design of smart hydrogels have transformed the way therapeutic agents are encapsulated and released in biological environments. On the other hand, the expeditious development of 3D printing technologies has revolutionized the fabrication of hydrogel systems for biomedical applications. By combining these two aspects, 4D printing (i.e., 3D printing of smart hydrogels) has emerged as a new promising platform for the development of novel controlled drug delivery systems that can adapt and mimic natural physio-mechanical changes over time. This allows printed objects to transform from static to dynamic in response to various physiological and chemical interactions, meeting the needs of the healthcare industry. In this review, we provide an overview of innovation in material design for smart hydrogel systems, current technical approaches toward 4D printing, and emerging 4D printed novel structures for drug delivery applications. Finally, we discuss the existing challenges in 4D printing hydrogels for drug delivery and their prospects. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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35 pages, 2582 KiB

Open AccessReview

Three-Dimensional (3D) Printing in Cancer Therapy and Diagnostics: Current Status and Future Perspectives

by Awaji Y. Safhi

Pharmaceuticals 2022, 15(6), 678; https://doi.org/10.3390/ph15060678 - 27 May 2022

Cited by 14 | Viewed by 4959

Abstract

Three-dimensional (3D) printing is a technique where the products are printed layer-by-layer via a series of cross-sectional slices with the exact deposition of different cell types and biomaterials based on computer-aided design software. Three-dimensional printing can be divided into several approaches, such as [...] Read more.

Three-dimensional (3D) printing is a technique where the products are printed layer-by-layer via a series of cross-sectional slices with the exact deposition of different cell types and biomaterials based on computer-aided design software. Three-dimensional printing can be divided into several approaches, such as extrusion-based printing, laser-induced forward transfer-based printing systems, and so on. Bio-ink is a crucial tool necessary for the fabrication of the 3D construct of living tissue in order to mimic the native tissue/cells using 3D printing technology. The formation of 3D software helps in the development of novel drug delivery systems with drug screening potential, as well as 3D constructs of tumor models. Additionally, several complex structures of inner tissues like stroma and channels of different sizes are printed through 3D printing techniques. Three-dimensional printing technology could also be used to develop therapy training simulators for educational purposes so that learners can practice complex surgical procedures. The fabrication of implantable medical devices using 3D printing technology with less risk of infections is receiving increased attention recently. A Cancer-on-a-chip is a microfluidic device that recreates tumor physiology and allows for a continuous supply of nutrients or therapeutic compounds. In this review, based on the recent literature, we have discussed various printing methods for 3D printing and types of bio-inks, and provided information on how 3D printing plays a crucial role in cancer management. Full article

(This article belongs to the Special Issue 3D Printing of Drug Formulations)

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