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SLS 3D printing for SOFs
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.
3D printing allows the production of objects of different sizes and shapes, according to a pre-established design. Therefore, it offers greater flexibility than conventional processes . Three-dimensional printing could help improve individualized oral therapy, especially solid oral forms (SOFs), which currently present limited options for individually designed doses. Indeed, while liquid forms can be easily dosed using oral syringes, they also present main disadvantages such as poor stability, administration errors and unpleasant taste. In contrast, solid forms, especially tablets, present higher stability, but the possibilities of dosing them individually are limited .
Selective laser sintering (SLS) is classified under the Powder Bed Fusion category according to the ASTM (American Society for Testing Material) . It involves the building of objects by necking powder particles using the energy provided by a laser . This additive manufacturing technique presents many benefits such as high resolution, the possibility of recycling the powder and the absence of pre-processing . Moreover, pharmaceutical manufacturing requires a higher threshold of quality and safety. This justifies the relevance of using pharmaceutical grade powders, which are recognized to be safe for the human body, but these materials should also be printable and remain stable during the printing process. The literature on SLS provides knowledge of the requirements for printability and stability of the feedstock materials . However, switching from conventional powders to pharmaceutical powders can be challenging .
2. Materials and Equipment
2.1. SLS Printer and Process Parameters
2.2. Raw Materials
Like FDM, SLS requires the use of thermoplastic polymers as matrices to carry drugs. This type of polymers present the ability to be processed and remolded upon thermal variations (heating and cooling) . Before sintering, the heating temperature is set below the melting temperature for semi-crystalline polymers or below the glass transition temperature for amorphous polymers . Then, the laser, depending on its scanning speed, will act as a final push to more or less fuse the powder particles. Several pharmaceutical thermoplastic polymers widely used for HME and FDM have also been explored for SLS such as copovidone (Kollidon VA64) , PEG-PVA (Kollicoat IR) , hydroxypropyl methylcellulose (HPMC) , ethylcellulose , acrylic polymers (Eudragit)  and polyethylene oxide (PEO) .
2.2.2. Active Pharmaceutical Ingredients (API)
2.2.3. Fillers and Other Components
3. Variability of the Structure
3.1. Variability of the Macrostructure with the Design
The ability to fabricate printlets presenting various geometries is not specific to the SLS technique but to 3D printing in general. However, precision varies from a printer to another and SLS shows good potential to produce highly complex structures with high resolution. The design of the reported SOFs varies from one study to another (Figure 3), depending on the intended application.
3.2. Variability of the Microstructure with the Process Parameters and the Material Attributes
3.2.1. Porosity of Printlets Produced by SLS
It is also interesting to note that the internal structure is not only influenced by the pre-established design but also by the printing parameters. As in the case of FDM, where slicing parameters such as infill rate and infill shape could modify the geometry of printlets and hence influence their properties ; SLS printing parameters such as laser scanning speed can also affect the size, the form and the distribution of pores by modulating the degree of sintering .
3.2.2. Critical Process Parameters and Material Attributes for Porosity in SLS
3.3. Relationship between Porosity–Mechanical Properties and Drug Release
3.3.1. Mechanical Properties
In general, hardness tended to decrease when the laser scanning speed was accelerated , or when the heating temperature was reduced . 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 . It is, therefore, necessary to determine the optimal energy interval that balances between the mechanical integrity and stability of the drug .
3.3.2. Drug Release
4. Amorphous Solid Dispersions (ASDs)
Difference scanning calorimetry (DSC) and X-Ray powder diffraction (XRPD) were used to determine the effect of sintering on the solid state of the material components by comparing the sintered printlets with their corresponding physical mixtures. DSC analysis showed that most of the printlets obtained by SLS presented a reduction or even a disappearance of the characteristic API melting peak. XRPD analysis generally corroborated the precedent results by demonstrating a more or less pronounced flattening of the specific crystalline peaks of the API. This suggests that the drug dissolves partially or totally into an amorphous form within the molten polymer during the sintering process . These results highlight the potential of SLS for the fabrication of solid amorphous dispersions.
5. Applications of SLS in Personalized Medicine
Porosity stands out as the main contribution of SLS technology, as both sintering parameters and material properties show the ability to modulate the internal structure of printlets. Therefore, orally disintegrating printlets appear as the most promising application for SLS of solid oral forms. Moreover, previous studies conducted on SLS of drug-delivery devices help to predict potential pharmaceutical applications such controlled-release printlets. In the long term, SLS could be an interesting asset for precision medicine, but in the meantime, there are still some technical and regulatory aspects to be addressed.
The entry is from 10.3390/pharmaceutics13081212
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