Resolution of Racemic Guaifenesin Applying a Coupled Preferential Crystallization-Selective Dissolution Process: Rational Process Development

Preferential crystallization is a cost efficient method to provide pure enantiomers from a racemic mixture of a conglomerate forming system. Exploiting small amounts of pure crystals of both enantiomers, several batch or continuous processes were developed, capable of providing both species. However, an intermediate production step has to be used when pure enantiomers are not available. In such cases, partially selective synthesis, chromatography, or crystallization processes utilizing chiral auxiliaries have to be used to provide the initial seed material. Recently, it was shown that a coupled Preferential Crystallization-selective Dissolution process (CPCD) in two coupled crystallizers can be applied if at least one pure enantiomer is available to produce both antipodes within one batch. The corresponding process is carried out in one reactor (crystallization tank) by seeding a racemic supersaturated solution with the available enantiomer at a certain temperature. The second reactor (dissolution tank) contains a saturated racemic suspension at a higher temperature. Both reactors are coupled via the fluid phase, allowing for a selective dissolution of the preferentially crystallizing enantiomer from the solid racemic feed provided in the dissolution vessel. The dissolution and crystallization processes continue until the solid racemic material is completely resolved and becomes enantiopure. At this point, both enantiomers can be harvested in their pure crystalline form. For a specific pharmaceutically relevant case study, a rational process design and the applied empirical optimization procedure will be described. The achieved productivities after optimization show the great potential of this approach also for industrial applications. Also, a strategy to control this process based on inline turbidity measurement will be presented

Gabapentin for tinnitus: a systematic review.

PURPOSE: The main aim of this study was to assess the effect of gabapentin on tinnitus via a systematic review. METHOD: An electronic search of literature as well as a hand search were conducted. Only double-blind randomized controlled trials (RCTs) that met all of the inclusion criteria were included in this review. The Cochrane Collaboration tool for risk of bias assessment was used to investigate the validity of the included studies. Meta-analysis was not appropriate due to inadequate details in reporting the data in the included studies. Hence, qualitative synthesis and interpretation of the data were carried out. RESULTS: Two studies that met the inclusion criteria were included in the review. Fourteen studies were excluded. There were substantive within-study clinical heterogeneities with regard to the baseline tinnitus handicap scores, duration of tinnitus, and severity of hearing loss in the included double-blind RCTs. CONCLUSION: The authors of both studies reported that gabapentin was not superior to placebo in their primary outcomes. However, following the assessment of risk of bias and within-study clinical heterogeneities, this review concludes that there is insufficient evidence regarding the effect of gabapentin on tinnitus

Fatigue Isotropy in Cross-Rolled, Hardened Isotropic-Quality Steel

Deformation and forging operations often introduce microstructural orientation and, therewith, mechanical anisotropy to steel. Flattened manganese sulfide inclusions are held responsible for a great part of fatigue anisotropy. Isotropic-quality (IQ) steel maintains the mechanical isotropy of the material, even after a deformation operation. Isotropic material generally contains little S and, therewith, few manganese sulfides. Further, the IQ steels used in this investigation were Ca treated. The Ca treatment improves the shape stability of the sulfides, even during a hot-working deformation. Two commercial materials were compared for their fatigue response, a standard medium-carbon steel with 0.04 wt pct S and a low-sulfur variant that underwent IQ treatment. The two batches were cross-rolled to plates with a deformation ratio of 4.5, leading to in-plane isotropy. Tension-compression fatigue testing was performed in longitudinal and short transversal directions relative to the rolling plane. The results showed strong anisotropy of the fatigue behavior for the standard material. The performance in the short transverse direction, with the principal stress perpendicular to the flattened inclusions, was inferior. The IQ material with nearly spherical inclusions was almost perfectly isotropic, with only slightly worse fatigue response in the short transverse direction. © The Minerals, Metals & Materials Society and ASM International 2008