(M1430-03-15) 3D Printing of Container Tablets: A New Paradigm for Multi-drug containing Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS)

Purpose: The past few years have seen an increasing interest in the use of 3-dimensional (3D) printing for pharmaceutical research and development of personalized drug delivery systems for better and more efficient therapeutic dosing while minimizing the possible adverse reactions. Around two-thirds of the new chemical entities being introduced in the market, are associated with some inherent issues like poor solubility and high lipophilicity.¹ Self-nanoemulsifying drug delivery systems (SNEDDS) provide a good and easy way to develop a platform for such drugs.² Combining this platform with 3D printing would further aid in developing new strategies for delivering poorly soluble drugs and personalized drug delivery with added therapeutic benefits. The goal of the study was to show the feasibility of incorporating the pre-formulated SNEDDS into 3D printed container systems, for the delivery of two different drugs with inherent poor solubility, namely, Curcumin (CUR) and Lansoprazole (LNS), while altering the release along with multi-drug delivery capabilities.

Methods: Drug-loaded SNEDDS were prepared by dissolving the model drugs CUR and LNS along with the oil, surfactant, and cosolvent in predetermined ratios followed by homogenization. The SNEDDS were assessed visually for their appearance and homogeneity was further evaluated by droplet size and polydispersity index (PDI) measurements. Microscopic characterization of the SNEDDS was performed using transmission electron microscopy (TEM). The antioxidant activity of the drug-free SNEDDS was estimated by DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical-scavenging assay and ABTS radical cation scavenging assay. These formulated SNEDDS were then loaded into hollow tablets printed using fused deposition modeling 3D printing technique. The filaments used for printing the hollow container system were made using filaments with a 1:1 composition of hydroxypropyl cellulose (HPC) and Soluplus. The wall diameter of the print was kept at 0.4 mm and 1 mm and the height of the container was set at 10 mm. Following this, a small volume pH shift dissolution study protocol was developed for evaluating the performance of these 3DP tablets containing SNEDDS as compared to pure SNEDDS.

Results: The droplet size analysis of the drug-free and drug-loaded SNEDDS formulations showed slightly different particle sizes upon aqueous dilution, as seen in Table-1. The SNEDDS were similar in structure and the formulation was homogeneous, transparent, and dispersed spontaneously upon aqueous dilution. SNEDDS showed a dose-dependent scavenging activity and the concentration required for a 50% antioxidant activity (IC₅₀) was 330.1 µg/ml in the DPPH method, while it was 393.9 µg/ml in the ABTS method, which can be seen in Figure-1. Pure SNEDDS showed an immediate drug release in the case of both drugs as compared to the release from the container system. The release from SNEDD loaded prints is associated with a certain lag time dependent on the HPC-Soluplus matrix to swell before the start of water ingress followed by release, as seen in Figure-2. Drug release of SNEDDS from the matrix can thus be controlled by varying the 3D printed matrix as per the intended use.

Conclusion: The SNEDDS showed balanced characteristics between high drug solubility, low droplet size, and good self-emulsification properties. Combining these two drug delivery platforms further opens more options for tackling a multitude of issues related to multi-drug delivery as well as delivery of drugs susceptible to degradation. The filament used for the preparation of the container system can be further explored to give a more versatile system for delivering an additional drug. We show an approach to delivering personalized medications for multi-drug regimens while combining different formulation approaches.

References: 1. Tambosi G, Coelho PF, Soares L, et al. Challenges to improve the biopharmaceutical properties of poorly water-soluble drugs and the application of the solid dispersion technology. Revista Materia. 2018;23(4). doi:10.1590/s1517-707620180004.0558
2. Shahba AAW, Mohsin K, Alanazi FK. Novel self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of cinnarizine: Design, optimization, and in-vitro assessment. AAPS PharmSciTech. 2012;13(3):967-977. doi:10.1208/s12249-012-9821-4

Acknowledgements:The research work reported herein was partly supported by Maniruzzaman’s start-up funds at the University of Texas at Austin, and the Faculty Science and Technology Acquisition and Retention (STARs) Award. The authors are thankful to the Researcher Supporting Project number (RSP-2021/301) at King Saud University, Riyadh, Saudi Arabia.


Table-1: Particle size measurements for SNEDDS.


Figure-1: Antioxidant activities of the drug-loaded SNEDDS; (A) DPPH scavenging activity; (B) ABTS scavenging activity.


Figure-2: In vitro drug release profile for (A) curcumin (CUR) and (B) lansoprazole (LNS), from pure SNEDDS, SNEDD loaded tablets from 1 mm and 0.4 mm wall diameter designs.