(M1230-01-05) Digital Light Processing (DLP) 3D Printed Tablets and Its Pharmacokinetic Evaluation in Rats

Purpose: The objective of the present study is to develop ibuprofen tablets using Digital Light Processing (DLP) three-dimensional printing and evaluate them via in vivo pharmacokinetic studies in rats.

Methods: The first step in this study was to optimize the resin formulation and printing parameters using the MicroDLP 3D printer. The printing process is illustrated in Figure 1. Box Behnken design was used to generate several batches, each with a unique pairing of the exposure time and resin composition, that were first tested for printability. The tablets that printed successfully were further tested in an in vitro setting. A TA-XT Plus Texture Analyzer was also used as a more accurate means of determining the peak breaking force of the tablets, the elastic modulus, and toughness of the tablets. Digital Scanning Calorimetry (DSC) was also utilized to determine the how well the active pharmaceutical ingredient (API) was integrated into the resin formulation. In vitro drug release was tested using a Vankel 10-1200 Model Paddle Dissolution Apparatus. Additionally, weight variation, friability, and hardness testing were used to evaluate printed tablets. Based off the results of the in vitro testing, a resin formulation was selected to print on the Phrozen Sonic 4k 3D printer, evaluate, and compare them to the results generated from tablets printed on the MicroDLP printer. The printer that produced the best tablets was selected to produce tablets for in vivo pharmacokinetic studies in rats. The selected formulation was tested against a commercial ibuprofen tablet to compare its pharmacokinetic activity in the in vivo setting.

Results: Batches 3, 7, and 10 from the box Behnken design were the only ones that successfully printed after the addition of the API to the formulation. These batches were further analyzed in an in vitro setting to determine which batch performed the best overall. The in vitro release data indicated that batches 3, 7, and 10 exhibited 45.526 ± 0.8759, 51.357 ± 1.512, and 64.119 ± 1.345% release of the API respectively after 24 hours. The results of the hardness test with the handheld tester indicated that batches 3, 7 and 10 exhibited a tensile strength of 2.625 ± 0.0388, 2.256 ± 0.027 and 2.765 ± 0.0751 MPa respectively. The results of the friability test showed that batches 3, 7, and 10 had percent changes in mass of 0.754, 1.197, and 0.688% respectively. As a result, batches 3 and 10 passed the friability test and batch 7 failed. The weight variation tests indicated that batches 3, 7, and 10 exhibited a percent variation in mass of 1.852 ± 1.326, 4.186 ± 2.955, and 1.768 ± 0.988% respectively. The results of the texture analysis of the batches 3, 7, and 10 yielded the yield point, toughness, and elastic modulus of each batch. The yield points for batches 3, 7, and 10 were 16.126 ± 1.657, 3.501 ± 0.553, and 13.902 ± 0.411 kg respectively. The elastic modulus values for batches 3, 7, and 10 were 11383.686 ± 825.627, 3650.022 ± 410.09, 11384.412 ± 386.562 g/mm respectively. The toughness values for batches 3, 7, and 10 were 2240.827 ± 338.636, 325.78 ± 68.83, and 1644.799 ± 64 g*mm respectively. Batch 10 was selected as the most suitable batch for further testing and was used to compare the MicroDLP and Phrozen Sonic 4k printers. The DSC thermograms obtained from the API showed an endothermic peak at 80 (⁰C), indicating its melting point. The thermogram of the formulated tablet loaded with the API did not show that same endothermic peak. The results of the in vitro release study showed that after 25 hours, the Phrozen and MicroDLP tablets showed 79 and 67% release respectively (Figure 2). Phrozen and MicroDLP tablets both followed Higuchi release patterns with R² values of 0.999 and 0.9978 respectively. The hardness test results showed that Phrozen and MicroDLP tablets had tensile strengths of 3.058 ± 0.155 and 2.765 ± 0.075 MPa respectively. The results of the weight variation tests showed that the Phrozen and MicroDLP tablets had a 2.022 ± 1.454 and 1.768 ± 0.988% deviation of mass. The Phrozen tablets failed the friability test with a 4.43% change in mass, but the MicroDLP tablets passed with a 0.754% change in mass. Tablets printed on the Phrozen printer were selected for the in vivo pharmacokinetic tests in rats. The formulation group exhibited an AUC of 318.97 ug/mL*hr compared to 66.56 ug/mL*hr shown in the control group (Figure 3). The formulation group also demonstrated a maximum concentration (Cmax) of 30.124 ug/mL at 2 hours compared to 9.715 ug/mL at 2 hours from the generic tablet (Figure 3).

Conclusion: In conclusion, we were able to experimentally optimize a resin formulation and use it to determine if different wavelengths of light used by different 3D printers affects the quality of tablets produced from them.

This figure compares the in vitro release of tablets made with batch 10 resin printed on the MicroDLP and Phrozen Sonic 4k printers.



This figure compares the in vivo drug release and pharmacokinetics of our experimental tablets made from the batch 10 resin and printed on the Phrozen Sonic 4k printer to commercially available ibuprofen tablets (Advil).



This figure indicates the different experimental batches generated by the Box Behnken Design. All of the resin compositions and their corresponding printing parameters that will be referenced in this work can be found here.