(M1030-09-49) Selective Laser Sintering 3D Printing for Improved Solubility of Indomethacin: A Study on Amorphous Drug Conversion

Purpose: The purpose of this study is to develop a solid dosage form of Indomethacin using the Selective Laser Sintering (SLS) 3D printing process. The main was to enhance the solubility of poorly soluble Indomethacin by converting the drug to its amorphous form.

Methods: Preparation of Powder Mixture: The drug, polymer, and colorant were sieved using a 150 μm mesh to optimize particle size for sintering. A 300 g batch of the powder mixture was prepared using a V-cone blender, consisting of 20% w/w Indomethacin, varying concentrations of the polymer, and 3% w/w Candurin gold sheen, which served as a laser energy absorber. Candurin was crucial because the drug and polymer did not effectively absorb the laser wavelength (λ = 445 nm). 3D printing process: The reservoir of the printer was filled with the powder mixture. A roller was used to apply each layer of powder onto the constructing platform. The surface printing temperature was kept at 80°C while the chamber was set at 105°C. Layer by layer, as specified in the. STL file, a 2.3 W blue diode laser that could scan at 50 to 300 mm/s sintered the powder until the print was finished. The powder mixture was loaded into the printer's reservoir. Each layer of powder was spread onto the building platform using a roller. The chamber temperature was set to 105°C, and the surface printing temperature was maintained at 80°C. A 2.3 W blue diode laser with scanning speeds ranging from 50 to 300 mm/s sintered the powder layer by layer according to the .stl file, until the completion of the print. After printing, the contents of the building platform were sieved to collect the printed tablets. Four formulations were printed at various laser speeds to identify the optimal parameters for the final formulations (Table 1). The printed tablets underwent further characterization for thermal analysis, solubility studies, tablet characterization, assay, and in vitro release testing. Stability studies were also conducted on the lead formulation.

Results: All the formulations were successfully printed using the Selective laser sintering 3D printing. The Morphology of all the printed tablets was Captured using a Dino microscope (Figure 1). DSC results of Formulations F₁, F_2, and F₃, with Laser scanning speed 200 mm/s, 250mm/s, and 300mm/s showed the amorphous drug conversion, whereas formulation F₄ only converted partially amorphous form. FTIR analyses showed that there is no interaction between the components. Drug content results showed that all the formulation has 95-110%.

Conclusion: An oral solid dosage form of Indomethacin as a model drug was printed successfully with SLS 3D printing technology to enhance the solubility by converting it into an amorphous form. Overall, these results suggest that SLS 3D printing holds promise as an effective and convenient 3D printing technology for oral solid dosage forms with more patient compliance and personalized medication. Invitro research for all the printed tablets will be performed for their invitro dissolution and stability studies to make SLS 3D printed tablets an effective dosage form for oral delivery.

References: 1. Awad A, Fina F, Goyanes A, Gaisford S, Basit AW. 3D printing: Principles and pharmaceutical applications of selective laser sintering. International Journal of Pharmaceutics. 2020 Aug 30;586:119594.
2. Thakkar R, Zhang Y, Zhang J, Maniruzzaman M. Synergistic application of continuous granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties. bioRxiv. 2021 Feb 14:2021-02.

SLS 3D printed Tablets F1,F2,F3 and F4.

Drug Content for Formulations F1, F2, F3 and F4.

Formulation composition