Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core–Shell, Multilayer, and Gradient Concentration Profiles

Abstract

Additive manufacturing (AM) appears poised to provide novel pharmaceutical technology and controlled release systems, yet understanding the effects of processing and post-processing operations on pill design, quality, and performance remains a significant barrier. This paper reports a study of the relationship between programmed concentration profile and resultant temporal release profile using a 3D printed polypill system consisting of a Food and Drug Administration (FDA) approved excipient (Pluronic F-127) and therapeutically relevant dosages of three commonly used oral agents for treatment of type 2 diabetes (300-500 mg per pill). A dual-extrusion hydrogel microextrusion process enables the programming of three unique concentration profiles, including core-shell, multilayer, and gradient structures. Experimental and computational studies of diffusive mass transfer processes reveal that programmed concentration profiles are dynamic throughout both pill 3D printing and solidification. Spectrophotometric assays show that the temporal release profiles could be selectively programmed to exhibit delayed, pulsed, or constant profiles over a 5 h release period by utilizing the core-shell, multilayer, and gradient distributions, respectively. Ultimately, this work provides new insights into the mass transfer processes that affect design, quality, and performance of spatially graded controlled release systems, as well as demonstrating the potential to create disease-specific polypill technology with programmable temporal release profiles.

3D Printed Tablets (Printlets) with Braille and Moon Patterns for Visually Impaired Patients

“…In this regard, three-dimensional (3D) printing may offer an elegant and practical solution to the problem. 3D printing is an additive manufacturing technique in which an object is built up in a layer-by-layer manner [10][11][12][13][14], based on a 3D model designed using computer-aided design (CAD) software [15][16][17][18][19]. At present, 3D printing is often used to produce engineering prototypes due to its fast production speed and cost-effectiveness [20][21][22][23].…”

Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective

“…Recently, there have been several publications that reported multi-drug printing using 3D printing [18,74,76,[177][178][179][180][181]. In 2015, Khaled et al used PAM printing to create a multi-drug pill with Medication adherence, or taking drugs correctly, is usually defined as the extent to which patients take drugs as prescribed by the doctor [171].…”

Additive Manufacturing of Precision Biomaterials

“…In addition, the combination of geometric design and FEA has been used to study the transport of small molecules through 3D composite objects. [133] This approach predicted the temporal release profile of different scaffolds, and is relevant to the design of patient-specific drug delivery systems via AM, which enable tailored therapeutic release profiles. Further, numerical simulations can be useful during manu facturing, for example, by defining suitable parameters for extrusion-based AM.…”

“…Adapted with permission. [133] Copyright 2015, Wiley-VCH. C) Example of personalized drug-loaded device for antiacne treatment.…”

“…Robotic dispensing of polypills comprised of Pluronic F-127 loaded with three common oral agents for the treatment of type 2 diabetes were designed with three independent release profiles, taking advantage of the ability to deposit material with a high degree of spatial control and different initial concentrations (Figure 5b). [133] Specifically, drug-loaded and nondrug-loaded materials were deposited to fabricate core-shell, multilayer, and gradient drug distributions in different compartments of the polypill, which were responsible for delayed, pulsatile, and constant drug release, respectively. The experimental release profiles were validated with diffusion-based mass transfer simulations.…”