(M0930-06-37) Investigation of 3D Printed Structures Employing Triply Periodic Minimal Surface (TPMS) Topology for Poorly Soluble Drugs: Part I - Development of 3D-Printed Hypromellose Structure with Ibuprofen

Purpose: Three-dimensional (3D) printing allows for precise control over the design and fabrication of complex structures, which can be customized to optimize drug release profiles[1, 2]. The application of 3D printing technology in fabricating Triply Periodic Minimal Surface (TPMS) structures was investigated utilizing AFFINISOL™ HPMC HME 15LV (hydroxypropyl methylcellulose) as a matrix for a model drug, Ibuprofen™ (IB). HPMC, known for its versatility and biocompatibility, serves as an adaptable foundation for drug delivery systems. The fabricated lattice structures exhibit precision in the control of pore size and geometry which is crucial for optimizing efficacy, modulating the release kinetics of drug (e.g., Ibuprofen) and minimizing side effects. These lattice structures can be employed in various delivery systems including personalized oral solid dosage forms (OSD), mucosal and topical delivery systems, as well as implants and prosthetics[3]. The results of this study show the methodology and characterization of TPMS lattice structures, highlighting their potential application in solubility enhancement, personalized medicine, and targeted drug delivery. Key parameters such as filament extrusion, TMPS structure and density, Ibuprofen content, and Ibuprofen release profiles are discussed to demonstrate the feasibility and effectiveness of 3D-printed HPMC lattice structures in oral solid dosage forms.

Methods: Preparation of IB-free and IB-impregnated filaments via hot melt extrusion: The formulation was made with 0%, 10%, and 20% IB in polymer matrix of AFFINISOL™ HPMC HME 15LV. A formulation of AFFINISOL™ HPMC HME 15LV with 5% Xylitol as plasticizer was also prepared for comparing rheology of different formulations. All formulations were extruded on a Leistritz Nano16 twin screw extruder. The obtained extrudates were ground and sieved through a 16-mesh sieve which were subsequently fed through a single-screw filament extruder (3Devo Filament Maker ONE Composer) via a 2 mm nozzle. 3D Printing: Using Prusa MK3, MK4 3D printers and employing IB-free and IB-laden filaments, Triply Periodic Minimal Surface (TPMS) structures, which were designed using nTop software, could be inserted into size 00 capsules were printed. Rheological Characterization: To investigate the printability of the HPMC with different concentration of IB, the rheological behavior of the samples was investigated using a 50 mm parallel plate configuration on Ares G2 Dynamic Mechanical Spectrometer in oscillatory mode. Drug Dissolution: The drug dissolution experiments were carried out using the USP dissolution Apparatus II, Agilent 708-DS with spectrophotometer Carey 60. The paddle speed and temperature were set to 150 rpm and 37 ± 0.5 °C, respectively. The release of IB was tested in dissolution media, phosphate buffer (pH 7.2) using a UV wavelength of 222 nm.

Results: Rheological behaviors of AFFINISOL™ HPMC with 0%, 10% and 20% IB were investigated. AFFINISOL™ HPMC and HPMC-IB solid dispersions demonstrated non-Newtonian (shear-thinning) pseudoplastic behavior. Such rheological behavior is consistent with previous publications[4, 5]. Inclusion of IB caused a significant drop in the complex viscosity compared with HPMC with 5% xylitol as plasticizers. This reduction is due to the plasticizing effect of the IB and the degree of reduction increases with increasing concentration of IB. TPMS lattice structures were printed using Prusa printers. Figure 1 shows an example of 3D printed insert made with AFFINISOL™ HPMC HME with 10% IB in TPMS diamond structure with 12% infill assembled in a commercial size 00 capsule. Similar release profiles were observed for all diamond structure with 12 to 20% infill made from HPMC and 10% IB.

Conclusion: AFFINISOL™ HPMC HME 15LV has been successfully used to 3D print TPMS lattice structure inserts that can be assembled into capsules.  It has also been found that AFFINISOL™ HPMC HME 15LV can be used as suitable matrix for incorporating drugs into 3D-printed structures.  Further investigations are planned to study how various TPMS lattice structures and densities affect drug release rates and to explore other poorly soluble drugs.

References: 1. Pan, S., et al., 3D-printed dosage forms for oral administration: a review. Drug Delivery and Translational Research, 2024. 14(2): p. 312-328.
2. Kim, J.H., K. Kim, and H.-E. Jin, Three-Dimensional Printing for Oral Pharmaceutical Dosage Forms. Journal of Pharmaceutical Investigation, 2022. 52(3): p. 293-317.
3. Hameed, P., et al., Biomorphic porous Ti6Al4V gyroid scaffolds for bone implant applications fabricated by selective laser melting. Progress in Additive Manufacturing, 2021. 6.
4. Chatterjee, T., et al., Rheology of Cellulose Ether Excipients Designed for Hot Melt Extrusion. Biomacromolecules, 2018. 11(19): p. 4430-4441.
5. Gupta, S.S., N. Solanki, and A.T.M. Serajuddin, Investigation of Thermal and Viscoelastic Properties of Polymers Relevant to Hot Melt Extrusion, IV: Affinisol™ HPMC HME Polymers. AAPS PharmSciTech, 2016. 17(1).


Figure 1. 3D printed insert (HPMC with 10% IB in TPMS diamond structure with 12% infill) in a commercial size 00 commercial capsule.