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Interfacial induction and regulation for microscale crystallization process: a critical review

《化学科学与工程前沿（英文）》 2022年第16卷第6期页码 838-853 doi: 10.1007/s11705-021-2129-8

摘要： Microscale crystallization is at the frontier of chemical engineering, material science, and biochemical research and is affected by many factors. The precise regulation and control of microscale crystal processes is still a major challenge. In the heterogeneous induced nucleation process, the chemical and micro/nanostructural characteristics of the interface play a dominant role. Ideal crystal products can be obtained by modifying the interface characteristics, which has been proven to be a promising strategy. This review illustrates the application of interface properties, including chemical characteristics (hydrophobicity and functional groups) and the morphology of micro/nanostructures (rough structure and cavities, pore shape and pore size, surface porosity, channels), in various microscale crystallization controls and process intensification. Finally, possible future research and development directions are outlined to emphasize the importance of interfacial crystallization control and regulation for crystal engineering.

关键词： interfacial crystallization heterogeneous nucleation supersaturation micro/nanostructure process control and intensification

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Effects of a structurally related substance on the crystallization of paracetamol

Ali SALEEMI, I.I. ONYEMELUKWE, Zoltan NAGY

《化学科学与工程前沿（英文）》 2013年第7卷第1期页码 79-87 doi: 10.1007/s11705-013-1308-7

摘要： Paracetamol (PCM) was crystallized from an isopropanol (IPA) solution containing various small amounts of metacetamol as an additive. The effect on the nucleation kinetics was studied by measuring the induction time to nucleation and the metastable zone width using focused beam reflectance measurements (FBRM) and attenuated total reflectance (ATR-UV/Vis) spectroscopy. Both the induction time and the metastable zone width were expressed as functions of the additive concentration. Small amounts of metacetamol (1–4 mol-%) were found to cause significant inhibition to the nucleation by extending both the induction time and the metastable zone width. A progressive change in the morphology of the paracetamol crystals from tabular to columnar habit was observed with increasing metacetamol concentration. The solvent also had a significant effect on the size of the paracetamol crystals as smaller crystals were obtained in IPA than in aqueous solution. The dissolution rate of paracetamol was improved by the incorporation of metacetamol with 4 mol-% having the most effect. A supersaturation control (SSC) approach was implemented for the PCM-IPA system with and without metacetamol in an attempt to control and obtain larger metacetamol-doped paracetamol crystals.

关键词： acetaminophen metacetamol crystallization metastable zone width induction time supersaturation control

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Oral product input to the GI tract: GIS an oral product performance technology

Gordon L. Amidon, Yasuhiro Tsume

《化学科学与工程前沿（英文）》 2017年第11卷第4期页码 516-520 doi: 10.1007/s11705-017-1658-7

摘要： The patient receives a pharmaceutical product, not a drug. The pharmaceutical products are formulated with a drug, an active ingredient to produce the maximum therapeutic effect after oral absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical products, we need an predictive tool for oral product performance in patients. Currently, we are a surprisingly long way from accomplishing that objective. If the 20th century was the ‘age of the drug’, i.e., the ‘magic bullet’, the 21st century must become the ‘age of the guided missile’, i.e., the delivery system, including the form of the active pharmaceutical ingredient (API) (‘drug’). The physical form of the drug and the delivery system must be optimized to maximize the therapeutic benefits of pharmaceutical products for humans. Oral immediate release (IR) dosage forms cannot be optimal for all drugs or likely even any drugs (APIs). Still, the formulation of pharmaceutical products has to be optimized for patients. But how do we optimize oral delivery of drugs? It is usually through ‘trial and error’, in humans! We need a better way to optimize the oral dosage forms. We have suggested to select different dissolution methodologies for this optimization based on BCS Subclasses. In this article, we present the predicted drug dissolution profile of ketoconazole as a model drug from our laboratory utilizing a gastrointestinal simulator (GIS), which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal tract-like environment and enable the control the gastric emptying rate. This dissolution system allows the monitoring of the drug dissolution phenomena and the observation of the supersaturation and the precipitation of pharmaceutical products, which is useful information to predict dissolution of pharmaceutical products. This system can provide the actual input needed to accurately predict the input into the systemic circulation required by many of the absorption prediction packages available today.

关键词： GIS in vivo predictive dissolution ketoconazole BCS subclassification supersaturation

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Purification and crystallization of xylitol from fermentation broth of corncob hydrolysates

Jinchao WEI, Qipeng YUAN, Tianxin WANG, Le WANG,

《化学科学与工程前沿（英文）》 2010年第4卷第1期页码 57-64 doi: 10.1007/s11705-009-0295-1

摘要： Xylitol, a five-carbon sugar alcohol, is a valuable sugar substitute, and widely used in the pharmaceutical, odontological and food industry due to its interesting properties. In the past decades, the xylitol industry has grown rapidly and more attention has been focused on xylitol purification, which possesses an important proportion of the whole industry. In our paper, the purification and crystallization of xylitol fermentation broth by biotechnology using corncob hydrolysates as substance were studied. An initial xylitol fermentation broth was decolored with activated carbon (1% M-1, 60°C, 165rpm), desalted with a combination of two ion-exchange resins (732 and D301), and residual sugars were separated with UBK-555(Ca). Then the solution was vacuum-concentrated up to supersaturation (750g/L xylitol). After adding 1% xylitol crystal seeds, the supersaturated solution was cooled to −20°C for 48h. The crystalline xylitol of a regular tetrahedral shape with purity 95% and crystallization yield 60.2% was obtained from the clarified xylitol fermentation broth. An intact, economical and environmental-friendly route of purification and crystallization of xylitol from fermentation of corncob hydrolysates was obtained, and its experimental procedure and data provided a sound basis for large-scale industrial production.

关键词： ion-exchange activated supersaturation tetrahedral substitute