68 research outputs found
An integrated view of theiInfluence of temperature, pressure, and humidity on the stability of trimorphic cysteamine hydrochloride
Understanding the phase behavior of pharmaceuticals is important for dosage form development and regulatory requirements, in particular after the incident with ritonavir. In the present paper, a comprehensive study of the solid-state phase behavior of cysteamine hydrochloride used in the treatment of nephropathic cystinosis and recently granted orphan designation by the European Commission is presented employing (high-pressure) calorimetry, water vapor sorption, and X-ray diffraction as a function of temperature. A new crystal form (I2/a, form III) has been discovered, and its structure has been solved by X-ray powder diffraction, while two other crystalline forms are already known. The relative thermodynamic stabilities of the commercial form I and of the newly discovered form III have been established; they possess an overall enantiotropic phase relationship, with form I stable at room temperature and form III stable above 37 degrees C. Its melting temperature was found at 67.3 +/- 0.5 degrees C. Cysteamine hydrochloride is hygroscopic and immediately forms a concentrated saturated solution in water with a surprisingly high concentration of 47.5 mol % above a relative humidity of 35%. No hydrate has been observed. A temperature composition phase diagram is presented that has been obtained with the unary pressure temperature phase diagram, measurements, and calculations. For development, form I would be the best form to use in any solid dosage form, which should be thoroughly protected against humidity.Postprint (author's final draft
Recommended from our members
Linking soil microbial community structure to potential carbon mineralization: A continental scale assessment of reduced tillage
Potential carbon mineralization (Cmin) is a commonly used indicator of soil health, with greater Cmin values interpreted as healthier soil. While Cmin values are typically greater in agricultural soils managed with minimal physical disturbance, the mechanisms driving the increases remain poorly understood. This study assessed bacterial and archaeal community structure and potential microbial drivers of Cmin in soils maintained under various degrees of physical disturbance. Potential carbon mineralization, 16S rRNA sequences, and soil characterization data were collected as part of the North American Project to Evaluate Soil Health Measurements (NAPESHM). Results showed that type of cropping system, intensity of physical disturbance, and soil pH influenced microbial sensitivity to physical disturbance. Furthermore, 28% of amplicon sequence variants (ASVs), which were important in modeling Cmin, were enriched under soils managed with minimal physical disturbance. Sequences identified as enriched under minimal disturbance and important for modeling Cmin, were linked to organisms which could produce extracellular polymeric substances and contained metabolic strategies suited for tolerating environmental stressors. Understanding how physical disturbance shapes microbial communities across climates and inherent soil properties and drives changes in Cmin provides the context necessary to evaluate management impacts on standardized measures of soil microbial activity
Diffusion suppression in silicon by substitutional C doping
\u3cp\u3eThe role of C as a suppressor of B, P, and In diffusion is widely known but the mechanisms involved are still poorly understood. This paper presents novel results on the diffusion of C at the nanometer scale, which clearly show that the suppression of diffusion arises from the expulsion of interstitials from the Cdoped region, caused by long-range migration of interstitial C atoms. Fundamental parameters for C diffusion (migration frequency and jump length) are presented and compared with existing data for B diffusion, and the results are placed in the context of a unified model of impurity diffusion.\u3c/p\u3
Experimental study on the mechanism of carbon diffusion in silicon
\u3cp\u3eCVD-grown lightly C-doped superlattices with peak C concentrations of 2.10\u3csup\u3e18\u3c/sup\u3e/cm\u3csup\u3e2\u3c/sup\u3e and 2.10\u3csup\u3e19\u3c/sup\u3e/cm\u3csup\u3e2\u3c/sup\u3e were annealed in NH\u3csub\u3e3\u3c/sub\u3e, N\u3csub\u3e2\u3c/sub\u3e/H\u3csub\u3e2\u3c/sub\u3e, N\u3csub\u3e2\u3c/sub\u3e, and O\u3csub\u3e2\u3c/sub\u3e ambient gases to investigate the influence of a range of point-defect conditions on C diffusion at the nanometer scale. C profiles were measured by Secondary-ion mass spectroscopy. The profiles exhibit exponential-like diffusion consistent with a 'long hop' diffusion process with a characteristic migration length λ (=19 ± 3 nm at 850 °C). Within experimental errors the value of λ is the same for all the ambient gases used, whereas the migration frequency g increases by two orders of magnitude as the ambient gas is changed from NH\u3csub\u3e3\u3c/sub\u3e ambient (interstitial undersaturation) to O\u3csub\u3e2\u3c/sub\u3e ambient (interstitial supersaturation), and decreases as a function of C concentration in the as-grown superlattice. The results confirm that C diffuses predominantly by a kick out mechanism under near-equilibrium diffusion conditions. Initial results support the chemical-pump model for suppression of diffusion in C-doped silicon.\u3c/p\u3
- …