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Pharmaceutical Development (pharmaceutical + development)
Selected AbstractsNanobiotechnology: From Molecules to SystemsENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 3 2004H. Klefenz Abstract Nanobiotechnology is a key enabling multidisciplinary field for medical, technological and biological research and development, medicine, pharmaceutical development, and analytical sciences. Its foundation is the selective integration of a multitude of endeavours, such as biotechnology, chemical and physical nanotechnology, materials sciences, chemistry, engineering, electronics and optronics targeting the construction of micro- and nano-arrays for analyzing complex mixtures of DNA, RNA, proteins, metabolites as well as the design of ultra-sequencing devices, microbial fuel cells, implantates, molecular motors, artificial organs, and nanorobots. The developments in nanobiotechnology benefit from and contribute to the scientific advances in the chemical and physical nanotechnologies, in particular with respect to materials, composites, nanostructuring techniques, carbon nanotubes, and nanoelectronics. [source] Enaminones: Exploring additional therapeutic activitiesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Ivan O. Edafiogho Abstract Enaminones, enamines of ,-dicarbonyl compounds, have been known for many years. Their early use has been relegated to serving as synthetic intermediates in organic synthesis and of late, in pharmaceutical development. Recently, the therapeutic potential of these entities has been realized. This review provides the background and current research in this area with emphasis of these agents as potential anticonvulsants, their proposed mechanisms of action, and as potential modulators of multidrug resistance (MDR). © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2509,2531, 2007 [source] Near infrared spectroscopy in the development of solid dosage formsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2007Eetu Räsänen The use of near infrared (NIR) spectroscopy has rapidly grown partly due to demands of process analytical applications in the pharmaceutical industry. Furthermore, newest regulatory guidelines have advanced the increase of the use of NIR technologies. The non-destructive and non-invasive nature of measurements makes NIR a powerful tool in characterization of pharmaceutical solids. These benefits among others often make NIR advantageous over traditional analytical methods. However, in addition to NIR, a wide variety of other tools are naturally also available for analysis in pharmaceutical development and manufacturing, and those can often be more suitable for a given application. The versatility and rapidness of NIR will ensure its contribution to increased process understanding, better process control and improved quality of drug products. This review concentrates on the use of NIR spectroscopy from a process research perspective and highlights recent applications in the field. [source] A sensitive and specific HPGPC-FD method for the study of pharmacokinetics and tissue distribution of Radix Ophiopogonis polysaccharide in ratsBIOMEDICAL CHROMATOGRAPHY, Issue 8 2010Xiao Lin Abstract Interest in antimyocardial ischemic activity of a graminan-type fructan with a weight average molecular weight of 4.8,kDa extracted from Radix Ophiopogonis (ROP) has necessitated the study of its pharmacokinetics and tissue distribution. For that, a simple HPGPC,FD method was developed for the sensitive and specific determination of FITC-ROP (fluorescein,isothiocyanate-labeled ROP) in plasma and rat tissues (heart, liver, spleen, lung, kidney, brain and stomach). The analyte was separated on a Shodex Sugar KS-802 high-performance gel column with 0.1,M phosphate buffer (pH 7.0) as mobile phase at a flow rate of 0.5,mL/min, and fluorescence detection at ,ex 495,nm and ,em 515,nm. The calibration curve for FITC-ROP was linear over the range 0.25,20.0 or 50.0,,g/mL in all studied biosamples with correlation coefficients >0.995. The inter-day and intra-day precisions of analysis were not more than 10%, and assay accuracy ranged from 93 to 105% for plasma and from 89 to 108% for tissue homogenates. This method has been confirmed here to be suitable for the study of pharmacokinetics and tissue distribution of ROP and the achieved results are highly instructive for the further pharmaceutical development of ROP, suggesting the promising application of the method to the increasingly important carbohydrate-based drugs. Copyright © 2009 John Wiley & Sons, Ltd. [source] Study on the enantiomeric ratio of the pharmaceutical substances alkannin and shikoninBIOMEDICAL CHROMATOGRAPHY, Issue 10 2004A. N. Assimopoulou Abstract The chiral pair alkannin and shikonin (A/S) are potent pharmaceutical substances with a wide spectrum of biological activity; their enantiomeric ratio does not in,uence the major biological activity studied hitherto. Nevertheless, in pharmaceutical development and approval of chiral drugs from the Health and Regulatory Authorities, full documentation of methods of analysis of enantiomeric drugs, is required in order to evaluate the enantiomeric purity of starting materials and ,nal products and to control the stability of enantiomers in pharmaceutical formulations under several experimental conditions. In the present study, the enantiomeric ratio of A/S was determined in several commercial samples of alkannin and shikonin and also the proportion of A/S derivatives in several Alkanna root samples, which are all used as active ingredients in pharmaceuticals. Light and air proved not to in,uence the enantiomeric ratio of A/S on a shikonin commercial sample, and temperature also did not alter the A/S ratio on shikonin and alkannin commercial samples. Microencapsulation of alkannin and shikonin commercial samples in ethylcellulose microspheres and also molecular inclusion of a shikonin commercial sample in , -hydroxypropyl-cyclodextrin, which are used as drug delivery systems, did not alter the A/S enantiomeric ratio. Copyright © 2004 John Wiley & Sons, Ltd. [source] Generation of high rapamycin producing strain via rational metabolic pathway-based mutagenesis and further titer improvement with fed-batch bioprocess optimizationBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2010Xiangcheng Zhu Abstract Rapamycin is a triene macrolide antibiotic produced by Streptomyces hygroscopicus. Besides its wide application as an effective immunosuppressive agent, other important bioactivities have made rapamycin a potential drug lead for novel pharmaceutical development. However, the low titer of rapamycin in the original producer strain limits further industrialization efforts and restricts its use for other applications. Predicated on knowledge of the metabolic pathways related to rapamycin biosynthesis in S. hygroscopicus, we have rationally designed approaches to generate a rapamycin high producer strain of S. hygroscopicus HD-04-S. These have included alleviation of glucose repression, improved tolerance towards lysine and shikimic acid, and auxotrophy of tryptophan and phenylalanine through the application of stepwise UV mutagenesis. The resultant strain produced rapamycin at 450,mg/L in the shake flask scale. These fermentations were further scaled up in 120 and 20,000,L fermentors, respectively, at the pilot plant. Selected fermentation factors including agitation speed, pH, and on-line supplementation were systematically evaluated. A fed-batch strategy was established to maximize rapamycin production. With these efforts, an optimized fermentation process in the larger scale fermentor was developed. The final titer of rapamycin was 812,mg/L in the 120,L fermentor and 783,mg/L in the 20,000,L fermentor. This work highlights a high rapamycin producing strain derived by mutagenesis and subsequent screening, fermentation optimization of which has now made it feasible to produce rapamycin on an industrial scale by fermentation. The strategies developed here should also be applicable to titer improvement of other important microbial natural products on an industrial scale. Biotechnol. Bioeng. 2010;107: 506,515. © 2010 Wiley Periodicals, Inc. [source] Autolabo: an automated system for ligand-soaking experiments with protein crystalsJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 4 2010Michihiro Sugahara Ligand soaking of protein crystals is important for the preparation of heavy-atom derivative crystals for experimental phasing as well as for large-scale ligand screening in pharmaceutical developments. To facilitate laborious large-scale ligand screening, to reduce the risk of human contact with hazardous ligand reagents and to increase the success rate of the soaking experiments, a protein crystallization robot `Autolabo' has been developed and implemented in the high-throughput crystallization-to-structure pipeline at RIKEN SPring-8 Center. The main functions of this robotic system are the production of protein crystals for experiments, the ligand soaking of these crystals and the observation of soaked crystals. The separate eight-channel dispensers of Autolabo eliminate the cross-contamination of reagents which should be strictly avoided in the ligand-soaking experiment. Furthermore, the automated approach reduces physical damage to crystals during experiments when compared with the conventional manual approach, and thereby has the potential to yield better quality diffraction data. Autolabo's performance as a ligand-soaking system was evaluated with a crystallization experiment on ten proteins from different sources and a heavy-atom derivatization experiment on three proteins using a versatile cryoprotectant containing heavy-atom reagents as ligands. The crystallization test confirmed reliable crystal reproduction in a single condition and the capability for crystallization with nucleants to improve crystal quality. Finally, Autolabo reproducibly derivatized the test protein crystals with sufficient diffraction quality for experimental phasing and model building, indicating a high potentiality of this automated approach in ligand-soaking experiments. [source] | |||||||||||||