Tuning Crystal Morphology of Succinic Acid Using a Polymer Additive

Abstract

The effect of the triblock co-polymer, Pluronic P123 (PP123) on the growth of succinic acid crystals from aqueous solutions is reported at two batch process scales: 10 mL and 350 mL. The presence of small quantities of PP123 is shown to modify the crystal morphology from plate-like crystals to block-like crystals, in a fully reproducible manner. Increasing the quantity of polymer present, or the concentration of succinic acid used, produces needle-like crystals that are less favorable for processing. In-line process analytical tools (FBRM, PVM and Raman) were implemented for the larger volume batch processes, allowing the crystallization to be monitored in real-time. The effect of the polymer on the metastable zone width (MSZW) has also been determined in designing the crystallization experiments and is presented. In addition, the effect of the individual blocks of the co-polymer, poly(ethylene glycol) and poly(propylene glycol) on the crystal morphology was examined and these findings, together with face indexing and knowledge of the underlying crystal structure, have allowed a possible mechanism to be constructed for the interaction of the polymer with the crystal surface. This mechanism is supported by subsequent re-crystallization experiments following washing of the block-like crystals with a non-polar solvent.

Serendipitous isolation of a disappearing conformational polymorph of succinic acid challenges computational polymorph prediction

“…The conformations in the observed salts of succinic acid (ESI Table S12) also suggest that local pH does not provide a simple explanation for the concomitant crystallization. The crystal morphology of β succinic acid is affected by a polymer additive, 33 showing that the growth kinetics are affected by the presence of other molecules. The conformational folding of the leucine dipeptide might aid the nucleation and growth of the γ form, altering the kinetic competition with the β form.…”

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

“…[38][39][40][41] It was suggested in an early study that the polymer (PVP) formed a netlike structure on crystal surfaces, from which the drug (sulfathiazole) grew into finger-like protrusions leading to rough surfaces. 42 A similar roughening effect was observed with felodipine crystals in the presence of HPMCAS under atomic force microscopy, in which the roughening effect was suggested to be the result of HPMCAS pinning the growth steps of felodipine crystals.…”

Influence of Cationic Surfactants on the Crystallization of Cis‐ and Trans‐Isomers

“…Impurities that have a molecular structure similar to the crystallizing compound (Agnew, Cruickshank, McGlone, & Wilson, ; Thomas, Wales, Zhao, & Wilson, ; Tian, Baldursdottir, & Rantanen, ) have the tendency to block the movement of surface steps, kinks, or terraces, and may be incorporated into the growing crystals (Simone, Steele, & Nagy, ), especially under unfavorable processing conditions (Meenan, Anderson, & Klug, ). In some cases, impurities are deliberately added to crystals to engineer crystallization with a desired morphology or polymorphic form (Alonzo et al, ; Ilevbare, Liu, Edgar, & Taylor, ; Klapwijk, Simone, Nagy, & Wilson, ; Lopez‐Mejías, Kampf, & Matzger, ; Oucherif, Raina, Taylor, & Litster, ; Simone, Cenzato, & Nagy, ; Trasi & Taylor, ; Vetter, Mazzotti, & Brozio, ; Yu, Dang, Black, & Wei, ).…”