Peer-Reviewed Journal Details
Mandatory Fields
Tierney, TB,Rasmuson, AC,Hudson, SP
2017
November
Organic Process Research & Development
Size and Shape Control of Micron-Sized Salicylic Acid Crystals during Antisolvent Crystallization
Published
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Optional Fields
PRECIPITATION MORPHOLOGY GROWTH NANOPARTICLES PARTICLES CALCIUM
21
1732
1740
During an antisolvent crystallization process, micron-sized crystals of salicylic acid in the particle size range 20 to 150 mu m were prepared under specific sets of crystallization conditions, with a focus on drug concentration, temperature, and solvent composition. For each experiment, the size outcome was determined by a number of knock on (often competing) influencing factors, including supersaturation, mass available for deposition during crystallization, and influence of temperature and solvent composition on crystallization kinetics. A certain fraction of the crystals, especially at higher solute concentration, developed a spectacular hollow shape with an almost perfect rectangular outer cross-section. A mechanistic explanation for the formation of hollow crystals is proposed. The use of additives during crystallization introduced further control over the size and, perhaps more noticeably, over the shape of the salicylic acid crystals. The lengths of salicylic acid crystals decreased to as low as 6 mu m with increasing concentration of HPMC. Both HPMC and CMC induced a change in the crystal habit from square prisms (for the pure system) to needles, due to the structural ability of these additives to selectively attach through hydrogen bonding to the dominating 110 faces of the crystals and slow down growth in that direction. SDS exhibited less of an influence on the size, but due to its attachment to the 001 faces, it prevented indentation of these faces from occurring and thus prevented the formation of hollow crystals.
10.1021/acs.oprd.7b00181
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