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bioRxiv · 10.1101/2021.04.09.439089

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

Thakkar, R.·Davis, D. A.·Williams, R. O.·Maniruzzaman, M.
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Abstract

This research study utilized a light-sensitive drug, nifedipine (NFD), to understand the impact of processing parameters, and formulation composition on drug degradation, crystallinity, and quality attributes (dimensions, hardness, disintegration time) of selective laser sintering (SLS) based 3D printed dosage forms. Selective laser sintering (SLS), in most cases, uses an ultraviolet laser source, and drugs tend to absorb radiation at varying intensities around this wavelength (455 nm). This phenomenon may lead to chemical degradation, and solid-state transformation, which was assessed for nifedipine in formulations with varying amounts of vinyl pyrrolidone-vinyl acetate copolymer (Kollidon(R) VA 64) and potassium aluminum silicate-based pearlescent pigment (Candurin(R)), processed under different SLS conditions in the presented work. After preliminary screening Candurin(R), surface temperature (ST), and laser speed (LS) were identified as the significant independent variables. Further, using the identified independent variables a 17-run, randomized, Box-Behnken design was developed to understand the correlation trends and quantify the impact on degradation (%), crystallinity, quality attributes (dimensions, hardness, disintegration time) employing qualitative and quantitative analytical tools. The design of experiments (DoE) and statistical analysis observed that LS and Candurin(R) (%wt) had a strong negative correlation on drug degradation, hardness, and weight, whereas ST had a strong positive correlation with, drug degradation, amorphous conversion, and hardness of the 3D printed dosage form. From this study, it can be concluded that formulation and processing parameters have a critical impact on stability and performance; hence these parameters should be evaluated and optimized before exposing light-sensitive drugs to the SLS processes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/439089v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1e3dd02org.highwire.dtl.DTLVardef@c2bfaforg.highwire.dtl.DTLVardef@1b6b712org.highwire.dtl.DTLVardef@ad35fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Thakkar, R., Davis, D. A., Williams, R. O., Maniruzzaman, M.. 2021-04-11. Selective Laser Sintering of a Photosensitive Drug: Impact of Processing and Formulation Parameters on Degradation, Solid-State, and Quality of 3D Printed Dosage Forms. https://doi.org/10.1101/2021.04.09.439089

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