In-line near infrared spectroscopy during freeze-drying as a tool to measure efficiency of hydrogen bond formation between protein and sugar, predictive of protein storage stability

Sugars are often used as stabilizers of protein formulations during freeze-drying. However, not all sugars are equally suitable for this purpose. Using in-line near-infrared spectroscopy during freeze-drying, it is shown here that hydrogen bond formation during freeze-drying, under secondary drying conditions in particular, can be related to the preservation of the functionality and structure of proteins during storage. The disaccharide trehalose was best capable of forming hydrogen bonds with the model protein, lactate dehydrogenase, thereby stabilizing it, followed by the molecularly flexible oligosaccharide inulin 4kDa. The molecularly rigid oligo- and polysaccharides dextran 5kDa and 70kDa, respectively, formed the least amount of hydrogen bonds and provided least stabilization of the protein. It is concluded that smaller and molecularly more flexible sugars are less affected by steric hindrance, allowing them to form more hydrogen bonds with the protein, thereby stabilizing it better

Emerging analytical separation techniques with high-throughput potential for pharmaceutical analysis, part II: Novel chromatographic modes.

In this review paper, the high-throughput potential of some novel chromatographic modes is surveyed. The modes are Hydrophilic Interaction Liquid Chromatography (HILIC), Supercritical Fluid Chromatography (SFC), and Polar Organic Solvent Chromatography (POSC). Their high throughput potential will be discussed in three domains, i.e. drug discovery, bio-analysis in clinical drug development, and quality control (QC) testing, and is illustrated with some examples.info:eu-repo/semantics/publishe

Emerging analytical separation techniques with high throughput potential for pharmaceutical analysis, part I: Stationary phase and instrumental developments in LC.

In recent years, a trend of change has been observed within pharmaceutical industry. As modern drug discovery has reached a remarkable level of complexity and drugs need to be discovered, developed and produced against strict timelines and within cost- and regulatory constraints, industry seeks "lean" solutions to increase productivity. Among them, increasing the sample throughput of the ever-growing number of necessary (routine) analyses has become a popular target to cut precious time. For the last thirty years, High-Performance Liquid Chromatography (HPLC) has been the leading technology when it comes to various analyses in pharmaceutical industry; however, its necessity of serial analyses taking typically 10-45 min has been a sample throughput-limiting barrier. Lately, the fundamentals of HPLC have been exploited to raise new technologies that can speed up analyses to ground breaking limits, without compromising separation efficiency. This paper reviews some promising technologies, i.e. totally porous sub-2microm particles accompanied by pressures up to 1000 bar (Ultra-Performance Liquid Chromatography or UPLC), fused-core particle technology, monolithic supports and High Temperature Liquid Chromatography (HTLC), having the potential to take LC to the next level in pharmaceutical industry. As each analytical method has its own demands, the advances of the above technologies are discussed for different applications in pharmaceutical analysis where high-throughput analysis can be meaningful, i.e. in a drug discovery and development setting, and in quality operations. Both chemical and biological pharmaceuticals are considered. We discuss the perspectives of these technologies and their realizations up to now in high-throughput pharmaceutical analysis.info:eu-repo/semantics/publishe

POSTER: Fuzzy Rough Set as feature selection for QSAR modeling of 2,4,5-trisubstituted imidazoles, nontoxic modulators of P-glycoprotein mediated multidrug resistance

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POSTER: Screening for antioxidant compounds in pressurized capillary electrochromatographic fingerprints from Mallotus species using partial least squares algorithms

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POSTER: Evaluation of sample matrix components affecting the separation efficiency of poliovirus particles in capillary electrophoresis

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POSTER: Process Analytical Technologies: an investment in understanding the pharmaceutical freeze-drying process

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POSTER: Screening for critical process parameters in a pharmaceutical freeze-drying process using a Plackett-Burman design and PAT tools

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POSTER: Screening for antioxidant compounds in Mallotus species using partial least squares regression models built on pressurized capillary electrochromatography fingerprints

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