Additive Manufacturing of PE/Fluorouracil Waffles for Implantable Drug Delivery in Bone Cancer Treatment

Salmoria, Gean Vitor; Vieira, F E; Ghizoni, G. B.; Gindri, Izabelle M.; Κanis, Luiz Alberto

doi:10.25125/engineering-journal-ijoer-jun-2017-12

Cited by 11 publications

(8 citation statements)

References 30 publications

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“…Hence, the mechanical strength is directly related to the porosity, as porous printlets present weak interparticular bonding and break easily. This is consistent with previous results on the influence of high laser energy density on improving stiffness of the sintered DDDs [ 55 , 56 , 57 , 58 , 59 , 62 , 63 ]. It is, therefore, necessary to determine the optimal energy interval that balances between the mechanical integrity and stability of the drug [ 60 ].…”

Section: Variability Of the Structuresupporting

confidence: 93%

“…Previous studies with DDDs have also demonstrated this effect on the printed parts. For instance, Ibuprofen [ 57 ] had a hardening effect because it intensifies sintering, while Hydroxyapatite [ 97 ] and Fluorouracil [ 62 ] decreased the hardness of the DDDs because they space out the polymer particles hindering its continuous melting.…”

Section: Variability Of the Structurementioning

confidence: 99%

“…Although the aim of this paper is not to review the work conducted on the production of DDDs, it is important to comment on the studies of SLS on SOFs in the light of the previous DDD choice of biopolymers and drugs. These DDDs were produced using biodegradable and biocompatible polymers including polycaprolactone (PCL) [53][54][55][56][57][58][59], polylactic acid (PLA) [53,60], polyethylene (PE) [61][62][63], polystyrene (PS) [64] and cellulose derivatives [65].…”

Section: Dimensions Of the Printlets Drug Release Profile Referencesmentioning

confidence: 99%

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Selective Laser Sintering (SLS), a New Chapter in the Production of Solid Oral Forms (SOFs) by 3D Printing

et al. 2021

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3D printing is a new emerging technology in the pharmaceutical manufacturing landscape. Its potential advantages for personalized medicine have been widely explored and commented on in the literature over recent years. More recently, the selective laser sintering (SLS) technique has been investigated for oral drug-delivery applications. Thus, this article reviews the work that has been conducted on SLS 3D printing for the preparation of solid oral forms (SOFs) from 2017 to 2020 and discusses the opportunities and challenges for this state-of-the-art technology in precision medicine. Overall, the 14 research articles reviewed report the use of SLS printers equipped with a blue diode laser (445–450 nm). The review highlights that the printability of pharmaceutical materials, although an important aspect for understanding the sintering process has only been properly explored in one article. The modulation of the porosity of printed materials appears to be the most interesting outcome of this technology for pharmaceutical applications. Generally, SLS shows great potential to improve compliance within fragile populations. The inclusion of “Quality by Design” tools in studies could facilitate the deployment of SLS in clinical practice, particularly where Good Manufacturing Practices (GMPs) for 3D-printing processes do not currently exist. Nevertheless, drug stability and powder recycling remain particularly challenging in SLS. These hurdles could be overcome by collaboration between pharmaceutical industries and compounding pharmacies.

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Section: Variability Of the Structuresupporting

confidence: 93%

Section: Variability Of the Structurementioning

confidence: 99%

Section: Dimensions Of the Printlets Drug Release Profile Referencesmentioning

confidence: 99%

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Selective Laser Sintering (SLS), a New Chapter in the Production of Solid Oral Forms (SOFs) by 3D Printing

et al. 2021

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“…However, incorporation of an absorbance enhancer could not be required since many biocompatible and biodegradable polymers absorb at the wavelength region of the CO 2 laser, as demonstrated by Salmoria et al [ 21 ]. This research team has printed drug delivery devices (DDDs) with a CO 2 laser using different polymers such as polycaprolactone [ 22 ] and polyethylene [ 23 ]. However, none of the studies conducted with the CO 2 laser on DDDs, evaluated drug stability [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Laser Sintering of Solid Oral Dosage Forms with Copovidone and Paracetamol Using a CO2 Laser

et al. 2021

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Material suitability needs to be considered for the 3D printing of solid oral dosage forms (SODFs). This work aims to assess the suitability of a CO2 laser (λ = 10.6 μm) for selective laser sintering of SODFs containing copovidone and paracetamol. First, physicochemical characterization of powders (two grades of copovidone, two grades of paracetamol and their mixtures at various proportions) was conducted: particle size distribution, morphology, infrared absorbance, flowability, and compactness. Then, printing was launched, and printability of the powders was linked to their physicochemical characteristics. The properties of the sintered SODFs were evaluated (solid state, general aspect, porosity, hardness, drug content and release). Hence, it was found that as copovidone absorbs at the laser’s wavelength, sintering was feasible without using an absorbance enhancer. Also, flowability, which mainly depends on the particle size, represents the first control line for “sinterability” as a fair flow is at least required. Low compactness of copovidone and mixtures reduces the mechanical properties of the SODFs but also increases porosity, which can modulate drug release. Moreover, the drug did not undergo degradation and demonstrated a plasticizer effect by lowering the heating temperature. In conclusion, this work proves the applicability of CO2 laser SLS printer to produce SODFs.

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“…Research in this area has demonstrated the application of SLS in 3D printing of modified-release oral solid dosage forms including orally disintegrating [ 13 ], immediate-release [ 14 , 15 ], and sustained release [ 16 , 17 ] tablets. Moreover, the versatility induced by AM has allowed the printing of multi-material [ 18 ], multi-drug printlets [ 19 ], multi-layered lattices [ 20 ], medical implants [ 21 , 22 , 23 ], and devices [ 24 ]. This previous and currently ongoing research depicts the potential of SLS 3D printing in manufacturing a wide range of robust pharmaceutical dosage forms with different functionalities.…”

Section: Introductionmentioning

confidence: 99%

Impact of Laser Speed and Drug Particle Size on Selective Laser Sintering 3D Printing of Amorphous Solid Dispersions

et al. 2021

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This research demonstrates the influence of laser speed and the drug particle size on the manufacturing of amorphous solid dispersions (ASD) and dosage forms thereof using selective laser sintering 3-dimensional (3D) printing. One-step manufacturing of ASD is possible using selective laser sintering 3D printing processes, however, the mechanism of ASD formation by this process is not completely understood and it requires further investigation. We hypothesize that the mechanism of ASD formation is the diffusion and dissolution of the drug in the polymeric carrier during the selective laser sintering (SLS) process and the drug particle size plays a critical role in the formation of said ASDs as there is no mixing involved in the sintering process. Herein, indomethacin was used as a model drug and introduced into the feedstock (Kollidon® VA64 and Candurin® blend) as either unprocessed drug crystals (particle size > 50 µm) or processed hot-melt extruded granules (DosePlus) with reduced drug particle size (<5 µm). These feedstocks were processed at 50, 75, and 100 mm/s scan speed using SLS 3D printing process. Characterization and performance testing were conducted on these tablets which revealed the amorphous conversion of the drug. Both MANOVA and ANOVA analyses depicted that the laser speed and drug particle size significantly impact the drug’s apparent solubility and drug release. This significant difference in performance between formulations is attributed to the difference in the extent of dissolution of the drug in the polymeric matrix, leading to residual crystallinity, which is detrimental to ASD’s performance. These results demonstrate the influence of drug particle size on solid-state and performance of 3D printed solid dispersions, and, hence, provide a better understanding of the mechanism and limitations of SLS 3D printing of ASDs and its dosage forms.

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Additive Manufacturing of PE/Fluorouracil Waffles for Implantable Drug Delivery in Bone Cancer Treatment

Abstract: Abstract-

Cited by 11 publications

References 30 publications

Selective Laser Sintering (SLS), a New Chapter in the Production of Solid Oral Forms (SOFs) by 3D Printing

Selective Laser Sintering (SLS), a New Chapter in the Production of Solid Oral Forms (SOFs) by 3D Printing

Selective Laser Sintering of Solid Oral Dosage Forms with Copovidone and Paracetamol Using a CO2 Laser

Impact of Laser Speed and Drug Particle Size on Selective Laser Sintering 3D Printing of Amorphous Solid Dispersions

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