Mechanistic understanding of the performance of personalized 3D-printed cardiovascular polypills: A case study of patient-centered therapy
The 3D printing has become important in drug development for patient-centric therapy by combining multiple drugs with different release characteristics in a single polypill. This study explores the critical formulation and geometric variables for tailoring the release of Atorvastatin and Metoprolol as model drugs in a polypill when manufactured via pressure-assisted-microextrusion 3D printing technology. The effects of these variables on the extrudability of printing materials, drug release and other quality characteristics of polypills were studied employing a definitive screening design. The extrudability of printing materials was evaluated in terms of flow pressure, non-recoverable strain, compression rate, and elastic/plastic flow. The extrudability results helped in defining an operating space free of printing defects. The Atorvastatin compartment of polypill consisted of mesh-shaped layers while Metoprolol compartment consisted of a core surrounded by a release controlling shell with a hydrophobic septum between the two compartments.
The results indicated that both the formulation and geometric variables govern the drug release of the polypill. Specifically, the use of HPMC E3 matrix, and a 2 mm distance between the strands at a weaving angle of 90° were critical in achieving the desired immediate-release profile of Atorvastatin. The core and shell design primarily determined the desired extended-release profile of Metoprolol. The carbopol and HPMC K100 concentration of 1% in the core and 10% in the shell and the number of shell layers in Metoprolol compartment were critical for achieving the desired Metoprolol dissolution. Polymer and Metoprolol content of the shell and shell-thickness affected the mechanical strength of the polypills. In conclusion, the 3D printing provides the flexibility for independently tailoring the release of different drugs in the same dosage form for patient centric therapy, and both the formulation and geometric parameters need to be optimized to achieve desired drug release.