Crystallization of Sulfathiazole in Gel: Polymorph Selectivity and Cross-Nucleation

Abstract

Form II, Form III, and Form IV of sulfathiazole (STZ) crystallized simultaneously from water by a cooling crystallization method. Thus, how to obtain the pure form of STZ represents a major challenge during the sulfathiazole crystallization process. Here we report that the pure Form III or Form IV of STZ can be selectively grown in agarose matrix by only adjusting the concentration of agarose. Interestingly, at a specific concentration range of agarose, the cross-nucleation of Form III on Form IV was observed. Furthermore, the mechanisms of agarose that affect the process of cooling crystallization of STZ were investigated, which indicated that the crystalline outcomes correlate strongly with the state of agarose gel that existed in solution. The highly reproducible and controllable results will help to broaden the application of gel in controlling crystallization of polymorph in the pharmaceutical industry. It also can be used as a guide for polymorphic screening of STZ from cooling crystallization.

Tuning Transport Phenomena in Agarose Gels for the Control of Protein Nucleation Density and Crystal Form

“…The growth of new polymorphs in gel media has been previously reported for proteins, when using peptide hydrogels [45,46], and for inorganic crystals grown in agarose [47], but in our case, the nucleation of a distinct crystal form was obtained due to the slow release of the protein from the agarose network into the precipitant compartment. We believe that the tuning of the protein mass transport imposed by the agarose gel played a pivotal role in the early stabilization of pre-nucleation clusters characterized by a different spatial arrangement of the macromolecules.…”

Agarose Gel as a Medium for Growing and Tailoring Protein Crystals

“…14 Moreover, Fmoc-FF hydrogels have allowed the incorporation of a very highly hydrophilic material, i.e., single-walled carbon nanotubes, within lysozyme crystals transforming them from an isolator to a conductor material. 15 Still, agarose is the most investigated hydrogel media, as it demonstrates incorporation as a simulating medium for biomineralization, 16 as a selector of a particular crystallization polymorph, 17 or even as a medium to observe the unusual phenomena named the Morse code effect, 18 to cite just a few recent works. In protein crystallization, agarose has been proven to facilitate the soaking of different molecules (ligands, cofactors, cryo-protectants, heavy atoms), 19,20 even when exposed to organic solvents (DMSO).…”

Simultaneous control of polymorphism and morphology via gelatin induction for concomitant systems: case study of sulfathiazole

“…The concomitant crystallization of ST forms II/III/IV from aqueous solution was conducted under the conditions in the literature, 35 and the three polymorphs were investigated in enhanced detail in this work. The three polymorphs can be roughly distinguished from the crystal habit (Fig.…”

“…[32][33][34] There are cases of trimorphic concomitant crystallization of ST from aqueous solution which have undesired crystal habits that result in poor processing performance. 35 Spherulite modification is a well-established method to control crystal habit. 36 The induction of spherulites is closely related to the initial crystal habit of the crystal.…”