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

Abstract

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.

Laser Sintering Approaches for Bone Tissue Engineering

“…Promising new advancements such as EBM [205] for metal printing to the use of bioactive coatings [204], antimicrobials, and even drug delivery methods for PBF [206][207][208][209][210][211], will ensure that novel implants can be provided to patients in a timely manner, with the appropriate legislation and oversight from government and regulators. In creating these personalized implants, humans will be equipped with the necessary tools to mitigate the impact of bone-related illnesses and the overall disease burden.…”

Selective Laser Sintering of a Photosensitive Drug: Impact of Processing and Formulation Parameters on Degradation, Solid State, and Quality of 3D-Printed Dosage Forms

“…This is because unlike photoabsorbing polymers such as polyamides (PA-12) designed for SLS printing in the case of pharmaceutical blends where polymers do not absorb the laser directly, photoabsorbing species like Candurin acts as a conducting excipient, which, in turn, causes the thermal transition of the polymer, resulting in sintering. 27 Thereby increasing the amount of Candurin at the cost of Kollidon VA 64 led to a reduction in the hardness and weight of the printlet. These findings add to the current understanding of the SLS process because properties such as weight critically influence the dose of the printlet and hardness impacts the stability and performance of the dosage forms.…”

“…For this experiment, the polymerʼs absorbance was not evaluated, as previous studies have demonstrated that it does not absorb visible radiation. 18,27 2.2.2. Critical Parameter Determination.…”

“…The prime objective of this study was to observe the absorbance behavior of NFD around 455 nm. For this experiment, the polymerʼs absorbance was not evaluated, as previous studies have demonstrated that it does not absorb visible radiation. , …”

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

“…Due to the combined application of heat and laser energy during the SLS process, an increased localised temperature first causes a sintering of the polymer and drug particles, followed by a rapid cooling to the surface temperature of the printer, which maintains the drug as intertwined in the polymer matrix in an amorphous form. Indeed, to date, a wide range of drugs, including paracetamol [ 22 , 23 ], ritonavir and copovidone [ 24 ], lopinavir [ 25 ], ibuprofen [ 26 ], indomethacin [ 27 ], ondansetron [ 28 ], and diclofenac sodium [ 29 ], as well as amlodipine and lisinopril [ 30 ], have been converted to a full or partial amorphous form post-printing using SLS technology.…”