Improving Content Uniformity of Drug-Loaded Filaments for 3D Printing Via Particle Engineering

Combining the use of twin-screw extrusion and three-dimensional (3D) printing has the distinct advantages of bioavailability enhancement of drugs as well as production of more complex-structured dosage forms and personalized drug products. However, producing drug-loaded filaments with good content uniformity (CU) and proper mechanical properties such as stiffness, i.e. neither too soft nor too brittle, is challenging. In this work, we consider improving the drug content uniformity by particle surface modification of crystalline micro-drug particles. In addition to improving drug content uniformity, another main objective is to increase the drug load. Towards that purpose, the effect of drug surface modification and three different types of plasticizers were investigated for a desired pharmaceutical formulation. Griseofulvin (GF) and hydroxypropyl cellulose (HPC, L grade) were used as the model BCS Class II drug and the polymeric matrix, respectively. Polyethylene glycol (PEG 3350), polyethylene oxide (PEO N10), and Kolliphor P407, were used as the plasticizers. The GF micro-particles with and without surface modification were dispersed into the molten polymeric matrix in the presence of a plasticizer using a co-rotating twin-screw extruder at elevated temperature, which was kept below melting point of GF. The surface modified GF was milled and coated with silica A200 with 100% surface area coverage via fluid energy mill. The produced filaments were evaluated for drug release rates using a USP II dissolution apparatus. The surface and cross-sectional morphology of the filaments were assessed by scanning electron microscopy (SEM). X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were used to characterize the drug crystal state and thermal properties of materials, respectively. The drug-loaded filaments were produced successfully via twin-screw process with desired properties for 3D printing. Formulations with micronized‒coated GF exhibited the fastest dissolution and the best CU. This study demonstrated the enhancement of drug load and content uniformity in filaments via particle engineering. The produced filaments can be used for 3D printing of structured dosage forms and personalized drug products.