Display omitted
The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D ...printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards.
The creation of an object by selective laser melting (SLM) occurs by melting contiguous areas of a powder bed according to a corresponding digital model. It is therefore clear that the success of ...this metal Additive Manufacturing (AM) technology relies on the comprehension of the events that take place during the melting and solidification of the powder bed. This study was designed to understand the generation of the laser spatter that is commonly observed during SLM and the potential effects that the spatter has on the processing of 316L stainless steel, Al-Si10-Mg, and Ti-6Al-4V. With the exception of Ti-6Al-4V, the characterization of the laser spatter revealed the presence of surface oxides enriched in the most volatile alloying elements of the materials. The study will discuss the implication of this finding on the material quality of the built parts.
3D printed polymeric drug-eluting implants Liaskoni, Athina; Wildman, Ricky D.; Roberts, Clive J.
International journal of pharmaceutics,
03/2021, Letnik:
597
Journal Article
Recenzirano
Display omitted
An extrusion-based 3D printer has been used for the manufacturing of sustained drug release poly(ε-caprolactone) (PCL) implants. Such implants can address issues of reduced patient ...compliance due to the necessary frequent administration of conventional drug delivery systems, such as tablets, capsules and solutions. The selected model drug for this study was lidocaine. Polycaprolactone core-shell implants, as well as polymeric implants with no barrier shell were printed with different drug loading, without the addition of solvents or further excipients. Scanning Electron Microscopy (SEM) analysis revealed the structural integrity of the printed formulations, while Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) were used to detect potential chemical interactions or modifications. Raman spectroscopy was also used to study material distribution in the prints. The drug release rate of the differently printed formulations was evaluated using a USP4 flow-through cell apparatus. All printed implants demonstrated sustained lidocaine release and the effectiveness of the PCL barrier in this regard. The Korsmeyer-Peppas model was suggested as the best fit to drug release profiles for all the produced implants. This work demonstrates that hot-melt extrusion-based 3D printing is a robust and promising technology for the production of personalisable drug-eluting implants.
The interest in Additive Manufacturing (AM) technology, also known as 3D printing, is unbroken. In many industries, however, stakeholders are struggling to understand AM's potential for manufacturing ...value creation. Most available literature on the cost of AM stresses the importance of ancillary processes and treats the relationship between process efficiency and capacity utilization. The most recently added - and overdue - aspect included in the extant AM costing literature considers the expected impact of so-called ill-structured costs, mainly relating to process failure and product rejection. Available research has investigated this aspect across a variety of technology types and process elements. This paper develops a new AM cost model that is generally specified so it can represent the probability and expected cost effect of failure events for all existing AM technologies. To demonstrate the implementation of this model, this paper applies it to the manufacture of pharmaceutical products (tablets) using the AM technology variant material jetting. The paper thus provides a robust indication of achievable unit cost levels, the cost effect of process failure, and also broaches the usefulness of cost models in guiding further process improvements.
Display omitted
In pharmaceutical technology, lipids and polymers are considered pillar excipients for the fabrication of most dosage forms, irrespective of the administration route. They play ...various roles ranging from support vehicles to release rate modifiers, stabilizers, solubilizers, permeation enhancers and transfection agents. Focusing on selected applications, which were discussed at the Annual Scientific Meeting of the Gattefossé Foundation 2018, this manuscript recapitulates the fundamental roles of these two important classes of excipients, either employed alone or in combination, and provides insight on their functional properties in various types of drug formulations. Emphasis is placed on oral formulations for the administration of active pharmaceutical ingredients with low aqueous solubilities or poor permeation properties. Additionally, this review article covers the use of lipids and polymers in the design of colloidal injectable delivery systems, and as substrates in additive manufacturing technologies for the production of tailor-made dosage forms.
Advances in bioprinting have enabled the fabrication of complex tissue constructs with high speed and resolution. However, there remains significant structural and biological complexity within ...tissues that bioprinting is unable to recapitulate. Bone, for example, has a hierarchical organization ranging from the molecular to whole organ level. Current bioprinting techniques and the materials employed have imposed limits on the scale, speed, and resolution that can be achieved, rendering the technique unable to reproduce the structural hierarchies and cell–matrix interactions that are observed in bone. The shift toward biomimetic approaches in bone tissue engineering, where hydrogels provide biophysical and biochemical cues to encapsulated cells, is a promising approach to enhancing the biological function and development of tissues for in vitro modeling. A major focus in bioprinting of bone tissue for in vitro modeling is creating dynamic microenvironmental niches to support, stimulate, and direct the cellular processes for bone formation and remodeling. Hydrogels are ideal materials for imitating the extracellular matrix since they can be engineered to present various cues whilst allowing bioprinting. Here, recent advances in hydrogels and 3D bioprinting toward creating a microenvironmental niche that is conducive to tissue engineering of in vitro models of bone are reviewed.
This review focuses on hydrogels and 3D bioprinting in bone tissue engineering for development of in vitro models of bone. It highlights challenges in recapitulating the biological complexity seen in bone and how synergistic application of dynamic hydrogels and innovative bioprinting pipelines can address these challenges to achieve bone models.
Display omitted
Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing ...enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector.
Abstract
Pristine graphene and graphene-based heterostructures can exhibit exceptionally high electron mobility if their surface contains few electron-scattering impurities. Mobility directly ...influences electrical conductivity and its dependence on the carrier density. But linking these key transport parameters remains a challenging task for both theorists and experimentalists. Here, we report numerical and analytical models of carrier transport in graphene, which reveal a universal connection between graphene’s carrier mobility and the variation of its electrical conductivity with carrier density. Our model of graphene conductivity is based on a convolution of carrier density and its uncertainty, which is verified by numerical solution of the Boltzmann transport equation including the effects of charged impurity scattering and optical phonons on the carrier mobility. This model reproduces, explains, and unifies experimental mobility and conductivity data from a wide range of samples and provides a way to predict a priori all key transport parameters of graphene devices. Our results open a route for controlling the transport properties of graphene by doping and for engineering the properties of 2D materials and heterostructures.
An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ...ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80%
w
/
w
). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.
Abstract
This study reports the successful fabrication of complex 3D metal nanoparticle–polymer nanocomposites using two‐photon polymerization (2PP). Three complementary strategies are detailed: in ...situ formation of metal nanoparticles (MeNPs) through a single‐step photoreduction process, integration of pre‐formed MeNPs into 2PP resin, and site‐selective MeNPs decoration of 3D 2PP structures. In the in situ formation strategy, a phase‐transfer method is applied to transfer silver and copper ions from an aqueous phase into a toluene solvent to disperse them in photoreactive monomers.The addition of a photosensitive dye, coumarin 30, facilitated the reduction of silver ions and improved the distribution of silver nanoparticles (AgNPs). This strategy is successfully used to produce other MeNPs, such as Cu and Au. The integration of pre‐formed MeNPs enabled highly controlled NP size distribution within the 2PP 3D structures with high‐fidelity To enable selective decoration of 2PP 3D surfaces with MeNPs, a multimaterial strategy is developed, with one of the resins designed for thiol‐ene reaction, which demonstrated selective binding to AuNPs. The successful development of complementary strategies for integration of MeNPs into 2PP resins offers exciting opportunities for fabrication of MeNP composites with sub‐micron resolution for applications from photonics to metamaterials and drug delivery.
PDF
