Application of 3D Printing in Personalized Drug Delivery Devices and Dosage Forms

Abstract

The evolution of 3D Printing (3DP) and its applications in various disciplines, including healthcare, in the past few years has been exemplary. The gradual shift from the conventional “one size fits all” concept to personalized drug delivery has been the overarching goal of additive manufacturing, whether in manufacturing dosage forms or drug delivery devices. 3D printing provides flexibility to construct devices and dosage forms of any complexities or geometrics efficiently. It utilizes the variation in the printing parameters and processes to result in desired functional changes such as drug release, loading, mechanical support, and improved patient compliance through personalization. The recent trends of 3DP research in pharmaceutical products have inclined towards personalization of the products, moving from ‘what all patients might want?” to “what each patient needs?’. Through this dissertation, we investigate a couple of research attempts that focus on designing drug delivery devices and formulations intended to facilitate personalization by tailoring the dose and optimizing surface, product design, and geometry. The research projects touch upon metal-based 3DP and polymer-based 3DP and fabricate and characterize drug delivery devices and dosage forms, enabling personalization. In Chapter 1, we touch upon the currently practiced 3DP techniques for the fabrication of drug products, dosage forms, and delivery devices with an elaborative review of recent advancements from the past five years, the newer generation technologies, and discuss some impending challenges associated with the translation of this technology from bench to bedside. In Chapter 2, we investigated polymeric-based coatings of natural origin on the metal device fabricated by Laser-Powder bed fusion and were able to control the release of dexamethasone for a week, intended for applications in acute orthopedic injuries. The surface roughness for the devices and coating techniques were optimized during this research work. In a follow-up research study on metal-based devices, in Chapter 3, the implants were coated with polymers of synthetic origin to prolong the elution of gentamicin for a month with a biphasic pattern of burst and sustained release. The biocompatibility and antibacterial/antibiofilm studies were conducted with the devices, and the results obtained were promising. This device offers application potential against post-surgical infections. In Chapter 4, we fabricated entirely polymeric-based scaffolds using a novel thermoplastic extrusion-based technology to achieve controlled release and investigated its potential to be used as orthopedic support through mechanical characterization. The Polycaprolactone (PCL) based scaffolds were able to tailor the nature of the release of the drug using variations in drug loading and printing parameters and were able to elute the drugs in a burst and sustained pattern for 2 months. The structural integrity of the scaffold was not compromised during the release, which reflected its potential to remain as a surgical support device while providing drug elution. In Chapter 5, we investigated three semi-solid extrusion technologies to fabricate fast-dissolving oral films. The optimized films were able to disintegrate within a minute and showed the potential to load personalized dosages of drugs through multilayered loading. The feasibility of using all three semi-solid extrusion technologies in a single table-top printer was investigated.