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Rheology of PVC Plastisol: Particle Size Distribution and Viscoelastic Properties.

Plastisols of poly(vinyl chloride), PVC, are suspensions of fine particles in plasticizer with about 50% resin volume fraction. Typically, the gross particle size ranges from 15 to 0.2 &mgr;m and smaller, where the common practice of spray-drying these resins and subsequent grinding of larger particles dictate the size ranges including agglomerates as well as the primary particles. The plastisol is a pastelike liquid, which may be spread to coat substrates. The coated substrates are heated in an oven to gel and fuse the material for producing uniform, rubbery products. Because the first step of processing is spreading the plastisol on a substrate, rheology at room temperature is obviously important. The material is thixotropic under very low stress. The flow behavior is pseudoplastic and exhibits dilatancy and fracture at high shear rate. This work is concerned with the pseudoplastic behavior but the dynamic mechanical measurements are employed instead of the usual steady-state shear flow measurements. This is because the steady shear may break up agglomerates. The dynamic measurements with small strain-amplitude avoid the break-up of the agglomerates. This is important, because this work is concerned with the effects of the particle size distribution on the material behavior. The frequency dependence of both viscous and elastic behavior is recorded and presented with samples varying in particle size distribution. Copyright 2001 Academic Press.

Journal Article↗

The use of tannin from chestnut (Castanea vesca).

After mimosa and quebracho extracts, chestnut extract is the third most important vegetable tannin used for leather production. It is produced only in Europe on the northern side of the Mediterranean sea. The extract is prepared by hot water extraction of the bark and timber, followed by spray-drying of the solution. Analysis shows that there are insignificant variations in extract quality between batches, so the extract can be used with modern automated leather production systems. The extract contains approximately 75 percent active tanning substances. The primary component is castalagin, along with smaller amounts of vescalagin, castalin, and vescalin. A castalagin-based pharmaceutical product is currently in use for prevention and treatment of diarrhea in pigs and cattle that is caused by changes in diet. The beneficial effect is due to prevention of water losses through mucous membranes. The castalagin may also form chelates with iron, which influences the reabsorption of the metal in the animal digestive tract.

Animals↗

Fortification of soft drinks with protein from cottage cheese whey.

Cottage cheese whey protein concentrates, prepared by preconcentration by ultrafiltration followed by gel permeation to remove low molecular weight materials, have the solubility, stability and flavor that make them suitable for fortification of soft drinks and related products. These concentrates are characterized by high levels of "available" lysine and by amino acid compositions indicating good nutritional value. Carbonated beverages prepared with conventional beverage ingredients and containing up to 1% by weight of the total beverage of added whey protein maintained clarity, color, and flavor during 203 days storage at room temperature. Spray dried whey protein concentrates were incorporated without adverse effects into commercial "ade" type powders. Clarity of 1% protein solutions at pH 2--3.5 was not impaired by heating for 6h at 80 degree, but some structural change occurred since an average of 37% of the protein precipitated on shifting pH to 4.7. Increased stability against heat denaturation under acidic conditions was conferred by some soft drink ingredients. Added sucrose reduced protein denaturation by 1/2 but sodium saccharin had no effect. The type of acid used also altered protein denaturation rate. While properly isolated whey protein concentrates have functional properties necessary for soft drink fortification, feasibility of use will depend upon cost.

Beverages↗

The effects of sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960) on ischemia-induced changes of brain acetylcholine and monoamine levels in gerbils.

The changes in acetylcholine (ACh), monoamine and monoamine metabolite levels following cerebral ischemia in Mongolian gerbils were examined. In addition, the effects of Sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960), which is a spray-dried mixture of 9 herbal drugs, on these changes were also examined. The dramatic decrement of ACh levels in ischemic gerbils was significantly inhibited by p.o. administration of TJ-960 at a daily dose of 3.5 g/kg or 700 mg/kg for one month. Norepinephrine (NE) was also reduced in all ischemic brain regions, and TJ-960 also recovered the level of NE. In ischemic gerbil brains, the dopamine (DA) levels decreased and its metabolites increased in the striatum, but DA and its metabolites in the thalamus + midbrain region increased. The serotonin (5HT) level was reduced in the cerebral cortex and hippocampus. TJ-960 inhibited these monoaminergic changes in ischemic gerbils. This suggests that TJ-960 may provide anti-ischemic action and beneficial effects on various symptoms induced by ischemia.

3,4-Dihydroxyphenylacetic Acid↗

[Quantitative analysis of auto-oxidation products of cholesterol in food of animal origin].

After extraction with methylene chloride, isolation of the unsaponifiable lipid fraction and enrichment by two-step column chromatography, the oxycholesterols were gas chromatographically separated in the form of their trimethylsilyl ethers on a thin film capillary and identified by mass spectrometry. The three major products of cholesterol autoxidation were cholest-5-en-3 beta, 7 alpha-diol(I) its 7 beta-epimer(II) and 5,6-epoxy-cholestan-3 beta-ol(III). In addition, traces of cholestan-3 beta, 5 alpha, 6 beta-triol and cholest-5-en-3 beta,25-diol were detected in some samples. Quantitative analysis was performed with cholest-5-en-3 beta,19-diol as internal standard. The highest concentrations of I-III were found in spray dried egg powders (total amount 15-60 micrograms/g). Parmesan cheese, butter oil and sausages contained significantly lower levels of I-III (total amount 0.1-2.6 micrograms/g). The concentrations of I-III increased strongly when butter oil and beef tallow were heated at 170 degrees C in the presence of air for a longer period.

Animals↗

Improved sensitivity of the BTPABA pancreatic function test in animals with meals of raw egg white.

An indirect exocrine pancreatic function test (PFT) which measures the ability of a test to hydrolyze a chymotrypsin-labile peptide (N-benzoyl-L-tyrosyl-PABA), was carried out in rats and swine with simulated partial exocrine pancreatic insufficiency. When spray-dried egg white (SDEW), which contains an inhibitor of chymotrypsin, was administered as a test meal with the PFT, the degree of pancreatic insufficiency was more pronounced. The results suggest that SDEW or raw egg while may be useful as a test meal to be given in conjunction with the PFT in humans in order to accentuate moderate degrees of pancreatic insufficiency and improve the sensitivity of this indirect test of pancreatic function.

4-Aminobenzoic Acid↗

[The behavior of polyphosphates during production and storage of long keeping milk products (author's transl)].

Polyphosphates added as stabilizers in the production process if liquid sterilized milk products are completely hydrolyzed to mono- and diphosphates. The diphosphate is further hydrolyzed during storage of the products. The extent of hydrolysis of diphosphate depends upon the processing conditions and may vary from production to production. During spray-drying of milk, the polyphosphates added are only partially hydrolyzed; further degradation of the polyphosphates takes place during storage.

Animals↗

Effects of protected cyclopropene fatty acids on the composition of ruminant milk fat.

Unsaturated fatty acids can be protected from ruminal hydrogenation, and when fed to lactating ruminants, the constituent acids are incorporated into milk triacylglycerols. By this means, it has been possible to reduce the melting point of milk triglycerides and to make softer butter fat. This report shows that, by feeding small amounts of protected cyclopropene fatty acids, one is also able to make harder butter fat. Sterculia foetida seed oil, a rich source of cyclopropene fatty acids, was emulsified with casein and spray dried to yield a free flowing dry powder. When this material was treated with formaldehyde and fed to lactating goats(ca. 1 g cyclopropene fatty acids per day), there were substantial increases in the proportions of stearic acid and decreases in the proportions of oleic acid in milk fat. Similar results were obtained when the formaldehyde-treated supplements were fed to lactating cows (ca. 3 g cyclopropene fatty acids per day). The effect was considerably less apparent when the S. foetida seed oil-casein supplement was not treated with formaldehyde, suggesting that cyclopropene fatty acids are hydrogenated in the rumen as are other unsaturated fatty acids. The effect of feeding protected cyclopropene fatty acids on the stearic:oleic ratio in milk fat is probably due to cyclopropene-mediated inhibition of the mammary desaturase enzymes.

Animals↗

A systematic approach to quantitation of ephedra alkaloids in natural health products.

A method for accurate determination of ephedrine (E) alkaloids in natural health products (NHP) is described. The NIST dietary supplement standard reference materials (SRMs) were selected for these studies. These SRMs comprise ground Ma Huang herb (Ephedra sinica Stapf.), a spray dried extract of the former, and commercial formulations derived from gel caps and a protein drink. The efficiency of sonication-assisted extraction and Soxhlet extraction was studied using both ammonium formate and potassium phosphate in 3% methanol as extraction media. The efficiency of SPE clean-up of the extract deteriorated rapidly when increasing amounts of sample matrix or analyte were processed, because of limited cartridge capacity. Quantitation by the method of additions was required to ensure the highest accuracy using both LC-UV and ES-LC-MS-MS techniques. Whereas the LC-UV method is more convenient and precise, the results are more questionable than ES-LC-MS-MS, because species-specific detection is not possible.

Alkaloids↗

Analysis of anthocyane glycosides in human serum.

Anthocyanins, natural food antioxidants, can be identified in human blood plasma using a restricted access phase for removal of the proteins and enrichment of the anthocyanins. In preliminary studies the spray dried elderberry juice was shown to have antioxidant activities in vitro. From the four known anthocyanins present in elderberry (Sambucus nigra) the two main components could be analysed quantitatively enabling their analysis in blood. Using a restricted access phase and a column switching set-up the injection of high volumes of concentrated protein solutions is possible. Additional, by using high injection volumes the sensitivity is increased due to a concentration of the analytes on the restricted access phase. The limit of quantification reached was 0.5 ng/mL. In this experiment the maximum concentration in blood (35 mg/mL) was observed after 1 h with a quick decay.

Anthocyanins↗

Orally administrable enterotoxigenic Escherichia coli vaccine encapsulated by ethylcellulose powder dispersion.

To overcome the limitations of injection administration to vaccinate neonatal piglets against diarrheal disease, an oral vaccine needs to be developed. Enteric microspheres of oral vaccines were developed by a co-spray drying process based on formalin-inactivated enterotoxigenic Escherichia coli antigens with various encapsulating materials. The encapsulating efficiencies of ECN7m, ECN14m and ECN22m (vaccine microsphere formulations) tested by extraction procedure are high, more than 85%. To assess enteric characteristics, an in vitro dissolution test was performed with microspheres. Formulations with ethylcellulose ECN14m and ECN22m allow controlled release in a neutral or basic environment and resisted acid damage. In all cases, 95% of the E. coli protein was released within 2 h at pH 6.8-7, but there was no release at pH 1.5-2. However, ECN7m was less acid-resistant and had lower release at low pH. In animal immunization tests, oral immunization with microspheres of formulations ECN14 and ECN22m effectively evoked both systemic IgG and mucosal IgA responses against E. coli whole cell antigens in mice. In the mice challenge test, orally administrable ECNm14 (12 mg) or ECN22m (12.6 mg) vaccine (i.e., encapsulating 3.0x10(9) cfu inactive bacterial mass) provided good protection from infection in animals.

Administration, Oral↗

Polymer particle-based micromolding to fabricate novel microstructures.

Conventional micromolding provides rapid and low-cost methods to fabricate polymer microstructures, but has limitations when producing sophisticated designs. To provide more versatile micromolding techniques, we developed methods based on filling micromolds with polymer microparticles, as opposed to polymer melts, to produce microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions. Polymer microparticles of 1 to 30 microm in size were made from PLA, PGA and PLGA using established spray drying and emulsion techniques either with or without encapsulating model drug compounds. These polymer microparticles were filled into PDMS micromolds at room temperature and melted or bonded together to form microstructures according to different protocols. Porous microstructures were fabricated by ultrasonically welding microparticles together in the mold while maintaining the voids inherent in their packing structure. Multi-layered microstructures were fabricated to have different compositions of polymers and encapsulated compounds located in different regions of the microstructures. More complex arrowhead microstructures were fabricated in a two-step process using a single mold. To assess possible applications, microstructures were designed as microneedles for minimally invasive drug delivery. Multi-layer microneedles were shown to insert into cadaver tissue and, according to design, detach from their base substrate and remain embedded in the tissue for controlled release drug delivery over time. We conclude that polymer particle-based micromolding can encapsulate compounds within microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions.

Biocompatible Materials↗

Intravenous hydrophobic drug delivery: a porous particle formulation of paclitaxel (AI-850).

PURPOSE: To develop a rapidly dissolving porous particle formulation of paclitaxel without Cremophor EL that is appropriate for quick intravenous administration. METHODS: A rapidly dissolving porous particle formulation of paclitaxel (AI-850) was created using spray drying. AI-850 was compared to Taxol following intravenous administration in a rat pharmacokinetic study, a rat tissue distribution study, and a human xenograft mammary tumor (MDA-MB-435) model in nude mice. RESULTS: The volume of distribution and clearance for paclitaxel following intravenous bolus administration of AI-850 were 7-fold and 4-fold greater, respectively, than following intravenous bolus administration of Taxol. There were no significant differences between AI-850 and Taxol in tissue concentrations and tissue area under the curve (AUC) for the tissues examined. Nude mice implanted with mammary tumors showed improved tolerance of AI-850, enabling higher administrable does of paclitaxel, which resulted in improved efficacy as compared to Taxol administered at its maximum tolerated dose (MTD). CONCLUSIONS: The pharmacokinetic data indicate that paclitaxel in AI-850 has more rapid partitioning from the bloodstream into the tissue compartments than paclitaxel in Taxol. AI-850, administered as an intravenous injection, has been shown to have improved tolerance in rats and mice and improved efficacy in a tumor model in mice when compared to Taxol.

Animals↗

Determination of the surface free energy of crystalline and amorphous lactose by atomic force microscopy adhesion measurement.

PURPOSE: This study was conducted to accurately measure the dispersive surface free energy of lactose solids in ordered and disordered states. METHODS: Atomic force microscopy (AFM) was used to determine the contact adhesion force between an AFM tip and lactose under low humidity (ca. 1% RH). The geometry of the tip contacting apex was characterized by scanning a porous aluminum film with ultrasharp spikes (radius 2-3 nm). A sphere vs. flat surface model was employed to relate the adhesion force determined to the surface energy based upon the Johnson-Kendal-Roberts theory. Spray-dried amorphous lactose in a compressed-disk form and single crystals of alpha-lactose monohydrate were prepared as model samples. RESULTS: The condition of the smooth sample surface and sphere-shaped tip used was shown to be appropriate to the application of the JKR model. The surface energy of crystalline [(0,-1,-1) face] and amorphous lactose was determined to be 23.3 +/- 2.3 and 57.4 +/- 7.9 mJ m(-2), respectively. CONCLUSIONS: We have demonstrated the capability of AFM to measure the dispersive surface free energy of pharmaceutical materials directly through a blank probe at the nanometer scale. These data, although consistent with results from more traditional methods, illustrate some unique attributes of this approach, namely, surface energies are directly derived from solid-solid interactions, measurements may be made on specific crystalline faces, and the potential exists to identify the submicron heterogeneity of organic solids in terms of their molecular energy states (such as ordered and disordered lactose).

Algorithms↗

High-performance thin-layer chromatographic method for the fluorescence detection of three nitroimidazole residues in pork and poultry tissue.

A high-performance thin-layer chromatographic method with fluorescence detection was developed for the qualitative determination of ronidazole, dimetridazole and their major metabolite, hydroxydimetridazole, in pork and poultry muscle. After extraction with dichloromethane and evaporation, the nitroimidazoles are redissolved in ammonium acetate buffer. The buffer phase is washed with hexane. The sample is cleaned-up by solid-phase extraction and the eluate evaporated. The final extract is resuspended in methanol and then spotted on an HPTLC plate. After multiple development with methanol and ethylacetate, the plate is dried, sprayed with pyridine and observed on an UV box (312 nm). The detection limits of this method are about 2 micrograms/kg for ronidazole, 5 micrograms/kg for dimetridazole and less than 5 micrograms/kg for hydroxydimetridazole. Validation was performed to levels of 10 micrograms/kg for dimetridazole, 5 micrograms/kg for ronidazole and 5 micrograms/kg for hydroxydimetridazole.

Animals↗

Degradation of poly(ester) microspheres.

Biodegradable polymeric microspheres have been prepared by spray drying, precipitation, rotary evaporation and press grinding methods. Erosion of microspheres of poly(lactide), poly(3-hydroxybutyrate), copolymers of lactide and glycolide, and copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate at 85 degrees C and 37 degrees C have been studied using ion chromatography, nuclear magnetic resonance, residual mass measurements, viscometry and gel permeation chromatography. Such studies demonstrated that these polyester matrices degraded via (1) random chain scission and (2) release of soluble monomeric and oligomeric products. Protein release from microspheres prepared by these methods indicated that most of the protein is released before the polymer matrix loses weight.

Biodegradation, Environmental↗

Fourier-transform infrared spectroscopic investigation of protein stability in the lyophilized form.

Upon the removal of water, proteins undergo a major, reversible rearrangement of their secondary structure, as revealed by FTIR spectroscopy. We have found herein that for recombinant human albumin (rHA) the extent of this structural change does not depend significantly either on the composition of the aqueous solution prior to lyophilization (protein concentration, pH, and the presence of excipients such as dextran or NaCl) or on the mode of dehydration (lyophilization, spray drying, or rotary evaporation), even though these factors profoundly affect rHA's solid-state stability against moisture-induced aggregation. In all cases, the alpha-helix content of rHA drops from 58% in solution to 25-35% in the dehydrated state, the beta-sheet content rises from 0 to 10-20%, and unordered structures increase from 40% to 50-60%. We have also investigated another model protein, hen egg-white lysozyme, and confirmed that it too undergoes a significant alteration of the secondary structure upon lyophilization. The extent of this structural reorganization has been found to be insensitive to the pH of the aqueous solution prior to lyophilization from pH 1.9 to 5.1, even though the thermal transition temperature (Tm) in aqueous solution over this range varies by 30 degrees C.

Dextrans↗

Feasibility of a reference material for staphylococcal enterotoxin A.

A reference material for staphylococcal enterotoxin A (SEA), was produced by spray-drying the toxin in milk. With this procedure the SEA was distributed homogeneously in the material. For ease of handling the reference material was encased in gelatin capsules, each containing 405 ng of SEA. Simply dissolving the milk powder in distilled water resulted in a 100% recovery of the SEA present. The reference material would appear suitable for testing laboratory performance, comparison of detection methods and to validation of extraction procedures.

Aerosols↗