Tablets are the most commonly used dosage form, and direct compression is the most desirable method of tablet production. Direct compression is most often only feasible if the powder mixture contains functional excipients that act as fillers and binders. One of the newer techniques for particle design of these excipients is spherical crystallization, where agglomerated, spherical particles with good flow properties and compressibility are obtained in the crystallization process. Most studies focus on the spherical crystallization of active ingredients, but this approach is also possible for the excipient particles design. In recent research, spherical agglomerated lactose has been developed, which has extremely good flow properties and compressibility, and is a suitable excipient for direct compression of tablets. In our work, we performed preliminary experiments of spherical crystallization with excipients that could replace lactose for direct compression of tablets. We studied two sugars: trehalose and glucose, and four sugar alcohols: erythritol, isomalt, mannitol, and xylitol. Ethanol and acetone were used as antisolvents. The product was compared with original particles. Spherical agglomerates of isomalt, mannitol and xylitol were also compared with functional excipients, that are intended for direct compression but are made by spray drying or granulation (GalenIQTM 721, Pearlitol 100 SD and Xylisorb 100DC). Particle size and density were measured for the newly formed and original particles, flow properties, morphology and structural properties were evaluated, for which we used thermal analysis and, if necessary, X-ray powder diffraction or IR spectroscopy. For the successful production of spherical agglomerates of selected excipients, a sufficiently high concentration of solution was essential to ensure adequate supersaturation when mixed with the antisolvent. For trehalose, isomalt and xylitol, preliminary tests (suitable flow properties and acceptable particle morphology) showed the feasibility of further experiments leading to optimization of spherical agglomerates with improved flow properties and suitable compressibility, while glucose did not give a suitable product. In the case of erythritol and mannitol, the properties of the original particles were not sufficiently improved. Spherical agglomerates of xylitol were also evaluated for compressibility, and it was found that these particles are less compressible in comparrison with commercially available xylitol particles for direct compression due to poor brittleness, which depends on the bonds between the base particles.
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