Crystal chemistry and solvent effects in polymorphic systems Sulfathiazole

Abstract. Solid-state characterisation of a drug following pharmaceutical processing and upon storage is fundamental to successful dosage form development. The aim of the study was to investigate the effects of using different solvents, feed concentrations and spray drier configuration on the solid-state nature of the highly polymorphic model drug, sulfathiazole (ST) and its sodium salt (STNa). The drugs were spray-dried from ethanol, acetone and mixtures of these organic solvents with water. Additionally, STNa was spraydried from pure water. The physicochemical properties including the physical stability of the spray-dried powders were compared to the unprocessed materials. Spray drying of ST from either acetonic or ethanolic solutions with the spray drier operating in a closed cycle mode yielded crystalline powders. In contrast, the powders obtained from ethanolic solutions with the spray drier operating in an open cycle mode were amorphous. Amorphous ST crystallised to pure form I at ≤35 % relative humidity (RH) or to polymorphic mixtures at higher RH values. The usual crystal habit of form I is needle-like, but spherical particles of this polymorph were generated by spray drying. STNa solutions resulted in an amorphous material upon processing, regardless of the solvent and the spray drier configuration employed. Moisture induced crystallisation of amorphous STNa to a sesquihydrate, whilst crystallisation upon heating gave rise to a new anhydrous polymorph. This study indicated that control of processing and storage parameters can be exploited to produce drugs with a specific/desired solid-state nature.

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“…These platelets are consistent with the morphology of both form III, characteristic of the starting material (Fig. 3d), and of form II (20).…”

Section: Sem Analysissupporting

confidence: 71%

Modification of the Solid-State Nature of Sulfathiazole and Sulfathiazole Sodium by Spray Drying

et al. 2012

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“…[19,24]. The NIR spectra of the five polymorphs and amorphous of FII and FIV [13,25]. As will be seen below this problem is somewhat reduced in this work as mixtures containing FIII are not observed in most cases.…”

Section: Nir Spectramentioning

confidence: 74%

Solid-State Transformations of Sulfathiazole Polymorphs: The Effects of Milling and Humidity

Erxleben

Hodnett

et al. 2013

Crystal Growth & Design

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The effect of milling on the solid-state transitions of sulfathiazole polymorphs in the absence and presence of solvent and excipients was monitored by X-ray powder diffraction (XRPD), attenuated total reflectance infrared (ATR-IR) and near-infrared (NIR) spectroscopy. Sulfathiazole forms FII-FV undergo a transformation toward the metastable FI, which involves an intermediate amorphous stage upon milling at ambient temperature. Milling FIII with catalytic amounts of solvent converts FIII to FIV or to mixtures of FI and FIV depending on the solvent used. Pure FIV can be easily prepared from FIII by this method. The physical stability of pure sulfathiazole forms in the presence of different levels of relative humidity (RH) was also investigated. At low RH all sulfathiazole forms are stable but at RH levels above 70% FII, FIII and FIV remain stable while FI and FV transform to mixtures of FII and FIV without any apparent change in the external form of the crystals. Co-milling FIII with a range of excipients gave results which depended on the excipient used and co-milling with cellulose gave samples which had an amorphous content that was stable at 10% RH for at least nine months at ambient temperature.

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“…39,40 Therefore according to Ostwald's Rule of Stages, amorphous sulfathiazole should initially produce form I as it is the least stable form, followed by a stepwise conversion, through the other metastable forms, to the thermodynamically most stable form. 34 Form I by its initial recrystallization back to form I is obeying the 11 Rule of Stages to some extent while amorphous form III shows a lesser effect in that it was found that the amount of form II increases with the cryo-milling time, as evidenced by an intensity increase in NIR bands at 6414 and 6112 cm -1 (Fig. 6).…”

Section: Stability Study Of Amorphous Sulfathiazole Samplesmentioning

confidence: 92%

“…The main differences between the polymorphs of sulfathiazole lie in hydrogen bonding and the packing of the molecules in the crystal lattice. 34 The physicochemical properties of the five forms have been described in detail. [35][36][37][38][39][40] Relative thermodynamic stabilities at 0 K are generally accepted to follow the order of the densities of the structures, i.e.…”

Section: Introductionmentioning

confidence: 99%

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

MacFhionnghaile

Caron

et al. 2013

Journal of Pharmaceutical Sciences

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Crystal chemistry and solvent effects in polymorphic systems Sulfathiazole

Cited by 170 publications

References 12 publications

Modification of the Solid-State Nature of Sulfathiazole and Sulfathiazole Sodium by Spray Drying

Modification of the Solid-State Nature of Sulfathiazole and Sulfathiazole Sodium by Spray Drying

Solid-State Transformations of Sulfathiazole Polymorphs: The Effects of Milling and Humidity

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

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