Releasing fast and slow: Non-destructive prediction of density and drug release from SLS 3D printed tablets using NIR spectroscopy
Selective laser sintering (SLS) 3D printing is a revolutionary 3D printing technology that has been found capable of creating drug products with varied release profiles by changing the laser scanning speed. Here, SLS 3D printed formulations (printlets) loaded with a narrow therapeutic index drug (theophylline) were produced using SLS 3D printing at varying laser scanning speeds (100–180 mm/s). The use of reflectance Fourier Transform – Near Infrared (FT-NIR) spectroscopy was evaluated as a non-destructive approach to predicting 3D printed tablet density and drug release at 2 h and 4 h. The printed drug products formulated with a higher laser speed exhibited an accelerated drug release and reduced density compared with the slower laser scanning speeds.
As an example, at 8 h, printlets fabricated at 180 mm/s reached 97% drug release whereas printlets at 140 mm/s and 100 mm/s reached only 75% and 29%, respectively. Univariate calibration models were developed based on a baseline shift in the spectra in the third overtone region upon changing physical properties. For density prediction, the developed univariate model had high linearity (R2 value = 0.9335) and accuracy (error < 0.029 mg/mm3). For drug release prediction at 2 h and 4 h, the developed univariate models demonstrated a linear correlation (R2 values of 0.9383 and 0.9167, respectively) and accuracy (error < 4.4%). The predicted vs. actual dissolution profiles were found to be statistically similar (f2 > 50) for all of the test printlets.
Overall, this article demonstrates the feasibility of SLS 3D printing to produce drug products containing a narrow therapeutic index drug across a range of drug release profiles, as well as the potential for FT-NIR spectroscopy to predict the physical characteristics of SLS 3D printed drug products (drug release and density) as a non-destructive quality control method at the point-of-care.
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Materials
Theophylline anhydrous USP grade (Sigma-Aldrich, 2022, UK) was used as a model narrow therapeutic index drug (MW 180.16 g/mol, solubility in water: 8.3 mg/mL (Sigma-Aldrich), >99% purity). Eudragit L100–55, a copolymer of methacrylic acid and ethyl acrylate (1:1 ratio) that dissolves at pH 5.5 was donated by Evonik, UK. Candurin Gold Sheen was purchased from Merck, UK. The salts for preparing the buffer dissolution media were purchased from VWR International Ltd., UK.
Sarah J. Trenfield, Xiaoyan Xu, Alvaro Goyanes, Martin Rowland, David Wilsdon, Simon Gaisford, Abdul W. Basit,
Releasing fast and slow: Non-destructive prediction of density and drug release from SLS 3D printed tablets using NIR spectroscopy,
International Journal of Pharmaceutics: X, 2022, 100148, ISSN 2590-1567,
https://doi.org/10.1016/j.ijpx.2022.100148.