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J Pharm Sci. 2019 Feb;108(2):914-928. doi: 10.1016/j.xphs.2018.09.030. Epub 2018 Oct 9.

Dropwise Additive Manufacturing of Pharmaceutical Products Using Particle Suspensions.

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Department of Chemical Engineering, Purdue University, West Lafayette, Indiana. Electronic address:
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana.
Department of Chemical Engineering, Purdue University, West Lafayette, Indiana.


The principal method of drug delivery is by oral solid doses, the production of which often necessitates multiple post-crystallization unit operations to ensure content uniformity or enhance bioavailability. As an alternative to conventional dose production methods, applications of additive manufacturing technologies based on solvent- or melt-based formulations have demonstrated the potential for improvements to process efficiency, flexibility, and dosing precision. Here we explore the use of particulate suspensions in a dropwise additive manufacturing process as a method for dosing active ingredients in crystalline form, which may be difficult to achieve via powder processing due to poor flow properties. By employing a fluid-based method, powder flow issues are alleviated and adaptation of the process to new particles/crystals is facilitated by dimensional analysis. In this work, a feasibility study was conducted using 4 active ingredient powders, each with non-ideal particle properties, and 2 carrier fluids, in which the active ingredient does not dissolve, to formulate suspensions for dose manufacturing; drug products were analyzed to show reproducibility of dosing and to assess preservation of particle size through the process. Performance across particle types is affected by particle size and shape, and is related through effects on the rheological properties of the formulation.


controlled delivery; crystal shape; formulation vehicle; microparticles; oral drug delivery; particle size; poorly water-soluble drugs; processing; solid dosage form; suspensions


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