Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of 'one size fits for all'. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing. Among all 3D printing processes, extrusion-based (both fused deposition modeling (FDM) and pressure-assisted microsyringe (PAM)) 3D printing is well researched for pharmaceutical manufacturing. It is important to understand which polymers are suitable for extrusion-based 3D printing of pharmaceuticals and how their properties, as well as the behavior of polymer–active pharmaceutical ingredient (API) combinations, impact the printing process. Especially, understanding the rheology of the polymer and API–polymer mixtures is necessary for successful 3D printing of dosage forms or printed structures. This review has summarized a holistic materials–process perspective for polymers on extrusion-based 3D printing. The main focus herein will be both FDM and PAM 3D printing processes. It elaborates the discussion on the comparison of 3D printing with the traditional direct compression process, the necessity of rheology, and the characterization techniques required for the printed structure, drug, and excipients. The current technological challenges, regulatory aspects, and the direction toward which the technology is moving, especially for personalized pharmaceuticals and multi-drug printing, are also briefly discussed.
Emulsion-based crystallization to produce spherical crystalline
agglomerates (SAs) is an attractive route to control crystal size
during downstream processing of active pharmaceutical ingredients
(APIs). However, conventional methods of emulsification in stirred
vessels pose several problems that limit the utility of emulsion-based
crystallization. In this paper, we use capillary microfluidics to
generate monodisperse water-in-oil emulsions. Capillary microfluidics,
in conjunction with evaporative crystallization on a flat heated surface,
enables controllable production of uniformly sized SAs of glycine
in the 35–150 μm size range. We report detailed characterization
of particle size, size distribution, structure, and polymorphic form.
Further, online high-speed stereomicroscopic observations reveal several
clearly demarcated stages in the dynamics of glycine crystallization
from emulsion droplets. Rapid droplet shrinkage is followed by crystal
nucleation within individual droplets. Once a nucleus is formed within
a droplet, crystal growth is very rapid (<0.1 s) and occurs linearly
along radially advancing fronts at speeds of up to 1 mm/s, similar
to spherulitic crystal growth from impure melts. The spherulitic aggregate
thus formed ages to yield the final SA morphology. Overall crystallization
times are on the order of minutes, as compared to hours in conventional
batch processes. We discuss these phenomena and their implications
for the development of more generalized processes applicable to a
variety of drug molecules. This work paves the way for microfluidics-enabled
continuous spherical crystallization processes.
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