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Chi A, Curi S, Clayton K, et al. Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics. Drug Deliv Transl Res. 2014;4(4):320-33doi: 10.1007/s13346-014-0198-7.
Chi, A., Curi, S., Clayton, K., Luciano, D., Klauber, K., Alexander-Katz, A., D'hers, S., & Elman, N. M. (2014). Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics. Drug delivery and translational research, 4(4), 320-33. https://doi.org/10.1007/s13346-014-0198-7
Chi, Albert, et al. "Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics." Drug delivery and translational research vol. 4,4 (2014): 320-33. doi: https://doi.org/10.1007/s13346-014-0198-7
Chi A, Curi S, Clayton K, Luciano D, Klauber K, Alexander-Katz A, D'hers S, Elman NM. Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics. Drug Deliv Transl Res. 2014 Aug;4(4):320-33. doi: 10.1007/s13346-014-0198-7. PMID: 25787065.
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Drug Deliv Transl Res. 2014 Aug;4(4):320-33. doi: 10.1007/s13346-014-0198-7.

Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics.

Drug delivery and translational research

Albert Chi, Sebastian Curi, Kevin Clayton, David Luciano, Kameron Klauber, Alfredo Alexander-Katz, Sebastian D'hers, Noel M Elman

Affiliations

  1. Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, 500 Technology Square, NE47-525, Cambridge, MA, 02139, USA.

PMID: 25787065 DOI: 10.1007/s13346-014-0198-7

Abstract

Rapid Reconstitution Packages (RRPs) are portable platforms that integrate microfluidics for rapid reconstitution of lyophilized drugs. Rapid reconstitution of lyophilized drugs using standard vials and syringes is an error-prone process. RRPs were designed using computational fluid dynamics (CFD) techniques to optimize fluidic structures for rapid mixing and integrating physical properties of targeted drugs and diluents. Devices were manufactured using stereo lithography 3D printing for micrometer structural precision and rapid prototyping. Tissue plasminogen activator (tPA) was selected as the initial model drug to test the RRPs as it is unstable in solution. tPA is a thrombolytic drug, stored in lyophilized form, required in emergency settings for which rapid reconstitution is of critical importance. RRP performance and drug stability were evaluated by high-performance liquid chromatography (HPLC) to characterize release kinetics. In addition, enzyme-linked immunosorbent assays (ELISAs) were performed to test for drug activity after the RRPs were exposed to various controlled temperature conditions. Experimental results showed that RRPs provided effective reconstitution of tPA that strongly correlated with CFD results. Simulation and experimental results show that release kinetics can be adjusted by tuning the device structural dimensions and diluent drug physical parameters. The design of RRPs can be tailored for a number of applications by taking into account physical parameters of the active pharmaceutical ingredients (APIs), excipients, and diluents. RRPs are portable platforms that can be utilized for reconstitution of emergency drugs in time-critical therapies.

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