(M1230-01-04) Development of 3D-Printed Gastro-Retentive Sustained Release Mini Device Using Ingestible Compounds

Purpose: The purpose of this study was to optimize a 3D-printed device for sustained release of a drug and create it using ingestible compounds.

Methods: In this study, Paracetamol (Acetaminophen) was chosen as API. Direct compression was used to prepare immediate-release tablets using lactose as a filler, Kollidon VA64 fine as a binder, sodium starch glycolate as a disintegrant, and stearic acid as a lubricant. 3D modeling of the device was carried out using Tinkercad, and devices by size and number of windows were printed using polylactic acid (PLA). The size and number of windows were optimized through the dissolution test. Afterward, Kollidon SR and microcrystalline cellulose (MCC) were mixed and extruded via hot melt extruder (HME) to produce ingestible filaments. A dissolution test was performed by printing an optimized device using this filament. All dissolution tests were performed using USP-Ⅱ apparatus, and finally the drug release profile kinetics were analyzed by fitting the experimental data.

Results: The tablet showed an immediate-release dissolution pattern in which dissolution was completed within 1 hour. Using PLA, the size of the window of device was fixed at 2 mm, and the number of windows was manufactured into 2, 4, and 6 windows, and the dissolution profiles were compared. The device with two windows was not suitable because the error was too large (up to 24.3%). In 4 and 6 windows, the dissolution profiles were similar, but 6 windows showed less error (up to 6.4%). The number of windows was fixed to 6, and the dissolution profiles were compared by making the windows 1mm, 2mm, and 3mm in size. The window size of 1mm was not suitable because the error was too large (up to 45.8%), and the 3mm was not suitable because dissolution was completed too quickly (T₉₀=4h). Finally, the number of windows of the device was decided to be 6 and the size of the windows to be 2mm. Kollidon SR has thermal expansion properties, so to control it, we extruded filaments in 8:2 mixture with MCC. The device has been successfully built and has been shown to float for over 10 hours. A slower and more consistent dissolution rate was found when comparing the dissolution profile with device made with PLA. As a result of kinetic analysis, it was confirmed that the tablet and the device made of PLA was a first-order release (R_sqr,tablet=0.9597, R_sqr,PLA=0.9652), whereas the device made of Kollidon SR was a zero-order release (R_{sqr,Kollidon SR}=0.9747), an ideal pharmacokinetic model for sustained release.

Conclusion: Using a simple window structure, the release rate of the drug was delayed by 8 times, and the device was successfully manufactured with a size and ingredients that can be safely taken. As a result of this study, it was possible to confirm the possibility of 3D printing technology in the pharmaceutical industry.

Figure 1. Optimized floating device design
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Figure 2. The difference in dissolution rate according to the number of windows (L) and the difference in dissolution rate according to the size of windows (R).



Figure 3. Dissolution profiles for tablets, devices made with PLA and devices made with Kollidon SR