ABSTRACT
A method for scale-up of a lubricant mixing process in a V-type blender was proposed. Magnesium stearate was used for the lubricant, and the lubricant mixing experiment was conducted using three scales of V-type blenders (1.45, 21 and 130 L) under the same fill level and Froude (Fr) number. However, the properties of lubricated mixtures and tablets could not correspond with the mixing time or the total revolution number. To find the optimum scale-up factor, discrete element method (DEM) simulations of three scales of V-type blender mixing were conducted, and the total travel distance of particles under the different scales was calculated. The properties of the lubricated mixture and tablets obtained from the scale-up experiment were well correlated with the mixing time determined by the total travel distance. It was found that a scale-up simulation based on the travel distance of particles is valid for the lubricant mixing scale-up processes.
Subject(s)
Lubricants/chemistry , Molecular Dynamics Simulation , Stearic Acids/chemistryABSTRACT
Ingestion of the toxic mushroom Boletus venenatus causes a severe gastrointestinal syndrome, such as nausea, repetitive vomiting, diarrhea, and stomachache. A family of isolectins (B. venenatus lectins, BVLs) was isolated as the toxic principles from the mushroom by successive 80% ammonium sulfate-precipitation, Super Q anion-exchange chromatography, and TSK-gel G3000SW gel filtration. Although BVLs showed a single band on SDS-PAGE, they were further divided into eight isolectins (BVL-1 to -8) by BioAssist Q anion-exchange chromatography. All the isolectins showed lectin activity and had very similar molecular weights as detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis. Among them, BVL-1 and -3 were further characterized with their complete amino acid sequences of 99 amino acids determined and found to be identical to each other. In the hemagglutination inhibition assay, both proteins failed to bind to any mono- or oligo-saccharides tested and showed the same sugar-binding specificity to glycoproteins. Among the glycoproteins examined, asialo-fetuin was the strongest inhibitor. The sugar-binding specificity of each isolectin was also analyzed by using frontal affinity chromatography and surface plasmon resonance analysis, indicating that they recognized N-linked sugar chains, especially Galbeta1-->4GlcNAcbeta1-->4Manbeta1-->4GlcNAcbeta1-->4GlcNAc (Type II) residues in N-linked sugar chains. BVLs ingestion resulted in fatal toxicity in mice upon intraperitoneal administration and caused diarrhea upon oral administration in rats.
Subject(s)
Agaricales/chemistry , Lectins/isolation & purification , Plant Lectins/isolation & purification , Amino Acid Sequence , Animals , Asialoglycoproteins , Carbohydrates/chemistry , Diarrhea/chemically induced , Electrophoresis, Polyacrylamide Gel , Fetuins , Glycoproteins/chemistry , Lectins/chemistry , Lectins/toxicity , Mice , Mycotoxins/chemistry , Mycotoxins/isolation & purification , Mycotoxins/toxicity , Plant Lectins/chemistry , Plant Lectins/toxicity , Rats , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , alpha-FetoproteinsABSTRACT
The dissolution property of a poorly water-soluble drug, flurbiprofen (FP), was improved by a novel dry coating method using a planetary ball mill. Several mixtures composed of water-soluble additives (D-mannitol, lactose, and erythritol), light anhydrous silicic acid, and flurbiprofen were prepared. These mixtures and several starches were co-ground in a planetary ball mill, and the surface of the starches was dry coated with the mixtures. The size, appearance, yield, and drug dissolution property of the dry coated preparations were evaluated, and the optimal formulation which improved the dissolution property of poorly water-soluble flurbiprofen was determined. The dissolution rate of FP was increased by dry coating of the surface of starches with microparticulated FP. It was further increased by co-grinding of FP, starch, and a water-soluble additive, or dry coating of the starch surface with microparticulated FP and light anhydrous silicic acid, as a glidant. These co-ground and dry coated preparations could be recovered from the pot of the planetary ball mill readily without adhesion to the inside wall of the pot. These are considered to be novel, industrially applicable methods for improving the dissolution rate of poorly water-soluble drugs.
