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PubMed2003

Effect of irradiation of individual feed ingredients and the complete diet on nursery pig performance.

A total of 1,210 nursery pigs was used in two experiments to evaluate the effects of irradiation of typical nursery diet ingredients, specialty protein products, and the whole diet on nursery pig performance. In Exp. 1, 880 barrows and gilts (15 +/- 2 d of age at weaning) were used in two growth trials (14 d and 12 d for Trials 1 and 2, respectively) to determine the effects of individual ingredient and whole-diet irradiation on nursery pig performance. Overall (d 0 to 14 of Trial 1 and d 0 to 12 of Trial 2), ADG was greater (P < 0.05) for pigs fed irradiated animal plasma compared with pigs fed the control, the diet containing irradiated microingredients, and the diet that was manufactured and irradiated. Also, pigs fed irradiated soybean meal had greater (P < 0.05) ADFI compared with pigs fed the manufactured diet that was irradiated. Pigs fed the diet containing irradiated animal plasma had improved feed efficiency (G:F; P < 0.05) compared with those fed the diet with irradiated microingredients and when all ingredients were irradiated before manufacturing of complete feed. Finally, pigs fed irradiated corn, whey, fishmeal, soybean oil, microingredients, or if all ingredients or the whole diet were irradiated, had similar ADG, ADFI, and G:F (P > 0.12) to control pigs. In Exp. 2, 330 nursery pigs (20 +/- 2 d of age at weaning) were used to determine the effects of irradiation of commercially available specialty protein products in diets for nursery pigs. Overall, ADG was greater (P < 0.05) when pigs were fed diets containing nonirradiated spray-dried animal plasma and egg combination (SDAPE) and dried porcine digest (DPD) compared with pigs fed the control diet containing no specialty protein products. In addition, G:F was improved (P < 0.05) when pigs were fed diets containing nonirradiated SDAPE, DPD, spray-dried beef muscle (SDBM), and spray-dried whole egg (SDWE) compared with pigs fed the control diet. Pigs fed irradiated SDAPE and SDBM had greater (P < 0.05) ADG than pigs fed the nonirradiated forms. Pigs fed irradiated SDBM had improved (P < 0.05) G:F compared with pigs fed the nonirradiated form. In Exp. 1 and 2, an irradiation treatment level of 8.5 kGy was effective in reducing the total bacterial concentration of all ingredients evaluated, as well as the whole diet in Exp.1. Irradiation of certain ingredients, but not the complete diet, increased growth performance of nursery pigs.

Animal Feed↗
PubMed2004

Pulmonary delivery of therapeutic peptides via dry powder inhalation: effects of micronisation and manufacturing.

Pulmonary drug delivery is increasingly appreciated as a route of administration for systemically acting proteins and peptides. A respirable particle size of the drug is a key requirement, but the fragile nature of many proteins may be a limitation for the application of conventional production processes. The aim of this study was to examine the effect of different micronisation processes on the degradation and aerodynamic properties of the GnRH-antagonist cetrorelix in order to enable its application by a dry powder inhaler (Novolizer). A modified pearl mill was used for milling in fluid propellant. Furthermore, a spray drying procedure was established using a novel process of atomisation and drying. Adhesive mixtures of lactose and 5-20% of micronised cetrorelix-acetate were prepared. Analysis by laser light scattering, HPLC, Karl Fischer, cascade impactor and scanning electron microscopy were performed to characterise the manufactured powders. Both micronisation procedures succeeded in producing small range particle size distributions, suitable for deep lung deposition (D50 = 1.6 microm for milling and 3.3 microm for spray drying). The pearl milled cetrorelix showed promising results when delivered by the Novolizer: a reproducible and highly efficient dispersion of the drug was achieved (around 60% of aerosolised drug < 5 microm). The spray dried drug was not suitable when processed as adhesive mixture.

Administration, Inhalation↗
PubMed1985

[Preparation and nutritional characteristics of a hydrolysate from pepitona (Arca zebra)].

Two soluble products resulting from the hydrolysis of pepitona (Arca zebra) were prepared as flour. Papain at its optimum hydrolysis conditions, previously established, was the enzyme used (40 degrees C for two hours at a pH of 7 in the proportion of 0.3% weight/enzyme/100 g meat). The hydrolysate obtained was then subjected to two different dehydration techniques: drum drying at 121 degrees C and 18 seconds retention, and spray drying at 101 degrees C and 40 psi pressure. The products were then stored for a five-month period at a temperature of 25 degrees C +/- 2 degrees C, time during which chemical determinations were performed in both hydrolysates. Findings showed that the time of storage does exert a significant effect of deterioration on the products. The greater and more significant quality losses occur during the first two months. The dehydration techniques used also affect significantly the soluble nitrogen content, and non-protein nitrogen and soluble solids content, as well as color of pepitona hydrolysates. Spray-drying dehydration technique does not have a significant deteriorating effect. Biological studies undertaken demonstrated that the quality of both hydrolysates is satisfactory from the nutritional and amino acid composition points of view. A protein efficiency ratio (PER) of 2.27 and 2.29 was determined for the hydrolysate dehydrated by drum drier and for the dehydrated by spray drier, respectively. With regard to amino acid composition, both had satisfactory levels of essential amino acids, with a lysine content of 6.9 g/100 g protein for the hydrolysate dehydrated by drum drying, and 8.6 g/100 g protein for the other hydrolysate dehydrated by spray drying.

Amino Acids↗
PubMed2004

Bupivacaine containing dry emulsion can prolong epidural anesthetic effects in rabbits.

To assess the prolongation of epidural bupivacaine by a novel lipid formulation, a physically stabilized bupivacaine containing dry emulsion was prepared by spray-drying. Bupivacaine release from the oil-in-water emulsion was studied using an in vitro two-phase stirred model, then the pharmacodynamic effects and the pharmacokinetics of bupivacaine from the spray-dried emulsion were evaluated and compared to a bupivacaine hydrochloride solution, following a two-period cross-over epidural administration in rabbits. The in vitro release characteristics suggested an extended release of bupivacaine from the emulsion compared to the solution. From the in vivo study, C(max) obtained with the emulsion (containing 5 mg bupivacaine) was not statistically different than from the solution (containing 2 mg bupivacaine) while T(max) was increased, suggesting a diminution of bupivacaine systemic absorption. The onset time of epidural anesthesia was similar for both formulations of bupivacaine used, while a significant blockade prolongation (360%) was observed with the emulsion compared to the solution, suggesting a controlled release of bupivacaine. Dry emulsions could be promising dosage forms to optimize the disposition of epidurally administered LAs.

Anesthesia, Epidural↗
PubMed2006

Screening for differences in the amorphous state of indomethacin using multivariate visualization.

The aim of this study was to examine molecular-level differences in the amorphous state of indomethacin prepared from both alpha- and gamma-polymorphs using various preparative techniques: milling, quench cooling of a melt, slow cooling of a melt and spray drying. X-ray powder diffraction (XRPD), polarizing light microscopy (PLM), differential scanning calorimetry, as well as mid-infrared (MIR), near infrared (NIR) and Raman spectroscopy were used to analyze the samples after preparation. Principal component analysis (PCA) was used to visualize the differences in the spectroscopic data. According to the XRPD and PLM measurements, all samples except the spray dried indomethacin were amorphous after preparation. Spray dried indomethacin had some remaining residual crystallinity. Differences in the amorphous samples could be found on molecular level: the milled samples clustered separately from the other amorphous samples in the PCA of MIR, NIR and Raman spectra. This could be due to either small degrees of undetected crystallinity remaining in the samples after milling or differences in the hydrogen bonding in the different amorphous samples of indomethacin. The spectroscopic techniques revealed different information about the samples. Raman spectroscopy was most sensitive to differences caused by the preparation techniques and degradation products. Multivariate methods, such as PCA, offer an efficient tool to screen for these differences in the amorphous state.

Chemistry, Pharmaceutical↗
PubMed2005

Dispersion and aggregation of nanoparticles derived from colloidal droplets under low-pressure conditions.

Formation of individually dispersed nanoparticles or compactly aggregated nanoparticles from sols via a spray-drying route at low pressure was investigated experimentally. Silica sol was used as a sample material. Effects of operating temperature, colloid size, sol concentration, pressure, pH and zeta potential of sols on the morphology of product particles were investigated. From the experimental results, it was shown that dispersed nanoparticles could be obtained at a relatively low pressure (20 Torr) and low temperature (200 degrees C). The experiment also showed that dispersed nanoparticles could be achieved by careful control of the interfacial energy (pH value) of the colloidal precursor. A possible mechanism of sol-to-dry-particle formation in the spray-drying process at low pressure is suggested, based on the experimental results and the available theories. This mechanism was able to explain the experimental results well.

Colloids↗
PubMed2007

Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin.

An injectable hyaluronic acid (HA) microhydrogel was successfully developed as a novel drug carrier for controlled release formulation of protein drugs. HA hydrogels were prepared by the disulfide bond formation of thiolated HA (HA-SH). EPO was loaded in situ during HA-SH hydrogel preparation using an accelerating agent of sodium tetrathionate. The gelation time was drastically reduced from a day to 30 min when sodium tetrathionate was added for HA-SH hydrogel preparation. In vitro release of EPO in PBS at 37 degrees C showed that EPO was rapidly released for 3 days with an initial burst and then slowly up to 9 days from HA-SH hydrogels. HA-SH microhydrogels were prepared by the reactive spray drying of diluted HA-SH precursor solution. The mean particle size was approximately 2.3 mum and the water content after spray drying was approximately 14%. Ellman's test showed that sodium tetrathionate contributed not only for rapid crosslinking reaction but also for the reduction of residual free thiol content in HA-SH microhydrogels after spray drying. EPO recovery from HA-SH microhydrogels after degradation with hyaluronidase SD was higher than 95%. The released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo release test of EPO from HA-SH microhydrogels in Sprague Dawley (SD) rats, elevated plasma concentration of EPO higher than 0.1 ng/mL, which is a critical minimal concentration for EPO efficacy, was maintained up to 7 days. There was no adverse effect during and after the in vivo tests.

Animals↗
PubMed1999

Methoxybutropate microencapsulation by gelatin-acacia complex coacervation.

Microcapsules of methoxybutropate solid particles or of an oily saturated solution of the same drug were prepared by complex coacervation between gelatin and acacia and dried with three different methods: isopropanol addition, spray-drying, and freeze-drying. Successively, microparticles were analyzed by infrared thermobalance, ultraviolet (UV) spectroscopy, optical and scanning electron microscopy, and sieves to find out parameters such as yield, moisture content, encapsulation percentage, morphology of solid particles, and particle size. Results highlighted that the most appropriate drying method for industrial purposes was spray-drying, particularly for oil-containing microcapsule formulations.

2-Propanol↗
PubMed2004

Dermal exposure to dry powder spray paints using PXRF and the method of Dirichlet tesselations.

This paper describes workplace dermal exposure measurements that were carried out by the Health and Safety Laboratory as part of the EU RISKOFDERM project to measure dust contamination. Exposure to dry powder spray paints was measured at five sites on 12 subjects. Twenty-two samples were obtained, of which eight contained triglycidyl isocyanurate (TGIC) and 14 did not. All subjects wore Tyvek whole body oversuits and some wore sampling gloves. These were either analysed in their entirety to extract the TGIC or surface scanned over representative areas using a portable X-ray fluorescence spectrometer (PXRF) to detect barium or titanium in the fillers of the paints. The method of Dirichlet tessellation was used to map the scans and the technique was developed further for these studies to extend measurements to gloves and to take limits of detection into consideration. The PXRF allowed dusts to be measured in situ that would otherwise be difficult to extract from the material and analyse by other means. The geometric mean surface loading rate of the 22 oversuits was 43 micro g/cm/(2)/h (GSD = 6.0) and of the 23 pairs of sampling gloves was 970 micro g/cm(2)/h (GSD = 8.6). Exposure patterns could be attributed to the arrangements of the subjects, spray booths and the workpieces. Similar exposures were found for TGIC and titanium fillers in factories with similar methods of ventilation.

Antineoplastic Agents↗
PubMed2000

Chitosan microspheres with hydrocortisone and hydrocortisone-hydroxypropyl-beta-cyclodextrin inclusion complex.

In the present study, an inclusion complex composed of hydrocortisone acetate (HC) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) was prepared by the spray-drying method. HC alone, HC inclusion complex or HC with HPbetaCD as a physical mixture were incorporated into chitosan microspheres by spray-drying. The inclusion complex and microspheres were characterized by X-ray powder diffractometry and differential scanning calorimetry (DSC). Microspheres were studied with respect to particle size distribution, drug content and in vitro drug release. The results indicate that the HCHPbetaCD inclusion complex is more water soluble than HC alone. The HC release rates from chitosan microspheres were influenced by the drug/polymer ratio in the manner that an increase in the release rate was observed when the drug loading was decreased. However, release data from all samples showed significant improvement of the dissolution rate for HC, with 25-40% of the drug being released in the first hour compared with about 5% for pure HC. The complexation method and microsphere preparation method (spray-drying) is simple with great potential for industrial production.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1998

Moisture content and particle size of dehydrated egg yolk affect lipid and cholesterol extraction using supercritical carbon dioxide.

Egg yolk was spray-dried under conditions to produce a small particle size powder and a large particle size powder. Particle size was determined using a Nikon Optiophot microscope. Spray-dried egg yolk was also adjusted to various moisture levels as follows: control (2 to 4% moisture), 7% moisture, and 12% moisture. Supercritical carbon dioxide extraction (SCE) of each of these moisture treatments at 45 C/306 atm using 30 g CO2/g of sample was completed. For the particle size study, 45 g CO2/g of sample at 45 C/306 atm was utilized. Particle size exhibited a significant effect on cholesterol and lipids extracted using SCE. As moisture content of dried egg yolk increased to 7%, there was a significant increase in lipids extracted using supercritical carbon dioxide. Moisture content had no significant effect on cholesterol extraction. After extracting SCE higher moisture spray-dried egg yolk, sponge cake volume was significantly reduced compared to that of the control. The reduced sponge cake volume may be due to protein denaturation.

Animals↗
PubMed2005

Survival of Lactobacillus plantarum 44a after spraying and drying in feed and during exposure to gastrointestinal tract fluids in vitro.

A good probiotic strain should be able to survive the conditions of handling and storage to be delivered in high concentration to the host. That is especially important when stressful conditions are prevalent in the carrier, for instance in low water content foods like animal feed. The aim of this research was to study the survival of the probiotic candidate Lactobacillus plantarum 44a after spraying and drying in feed, and during storage and exposure to gastrointestinal tract fluids in vitro. In addition, the viability of the strain during exposure to distilled water and 2% NaCl was studied. Feed was sprayed with a suspension of asymptotically equal to 2 x 10(10) CFU of L. plantarum 44a in 10, 15, 20, 25 and 30% v/w of the feed and dried to constant weight (6% moisture) in a convective oven at 25 degrees C. L. plantarum 44a survived 14.67, 36, 51.86, 78.9 and 105.3% respectively in relation to the original % v/w of the feed. After 3 weeks of storage at 25 degrees C, survival was similarly low in all the treatments. L. plantarum 44a stored in feed containing 13% moisture, vacuum-packaged and stored in refrigeration, maintained high viability (approximately 100%) after 1 year of storage. Survival was not affected after feed-containing lactobacilli was exposed to gastrointestinal fluids in a simulation model. Viability of L. plantarum 44a as a cell suspension in PBS added directly to distilled water or distilled water with 2% NaCl was maintained up to 48 h; after 72 h, viability started to decline. It is concluded that L. plantarum 44a maintained high viability after being dried and stored in feed even after exposure to gastric and intestinal fluids in vitro.

Animal Feed↗
PubMed2002

Spray-freeze-drying for protein powder preparation: particle characterization and a case study with trypsinogen stability.

This work investigates the use of spray freeze-drying (SFD) to produce protein loaded particles suitable for epidermal delivery. In the first part of the study, the effects of formulation and process conditions on particle properties are examined. Aqueous solutions of trehalose produce SFD particles in the size range 20-80 microm, with a smooth, textured surface, but having high internal porosity. The latter was visualized using SEM and a novel particle embedding and sectioning technique. Use of an annealing step during the freeze-drying cycle caused the particles to shrink, reducing hereby porosity and also the measured rate of moisture uptake into these amorphous particles. SFD pure mannitol was approximately 40% amorphous, but not hygroscopic. Incorporation of dextran 37,500 into a combined amorphous trehalose/mannitol formulation led to increased particle shrinkage and lower particle porosity on annealing. The model protein trypsinogen lost approximately 15% activity during SFD of solutions containing 50 mg/mL protein, but was only marginally aggregated (1.4%). It is suggested that trypsinogen forms an irreversible partially unfolded state or molten globule on SFD/rehydration. The pure protein was also partially inactivated without aggregation during atomization into air. Surprisingly, neither activity loss nor aggregation were detected on atomization of the protein solution into liquid nitrogen. Quench-freezing of small droplets may reverse the partial unfolding of trypsinogen occurring on atomization into air. The origin of the trypsinogen inactivation during SFD must therefore be the subsequent freeze-drying step of this multistep process. Isolated freeze drying of trypsinogen produces strong aggregation and equivalent inactivation. This result suggests that trypsinogen behaves differently during freeze drying from frozen droplets and from bulk solution in a vial. In the former case the protein forms an irreversible partially unfolded state, whereas in the latter case aggregates are formed. Trypsinogen inactivation during SFD could be completely prevented by the presence of trehalose in the formulation. Electron Spectroscopy for Chemical Analysis (ESCA) showed a high surface excess of the protein in the SFD particles, which was reduced on inclusion of Polysorbate 80, but not trehalose. Taken together, these results help to elucidate the complex destabilization behavior of trypsinogen during SFD.

Chromatography, Gel↗
PubMed2005

Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

Administration, Oral↗
PubMed1996

[Crystal forms, improvements of dissolution and absorption of poorly water-soluble (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022)].

Polymorphs of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022) were investigated. Two crystalline forms (alpha- and beta-forms) of YM022 were confirmed by powder X-ray diffractometry and differential scanning calorimetry. alpha- And beta-forms were obtained by recrystallization from ethanol and ethanol: water (5:1), respectively. Amorphous YM022 was obtained by spray drying of YM022 methanol solution. Since both crystalline and amorphous YM022 were sparingly soluble in water, solubilization of YM022 by solid dispersion and wet grinding methods were performed. In vitro dissolution study and in vivo absorption study in dogs were carried out using spray-dried solid dispersion, heat-treated solid dispersion and mechanical mixture. Spray-dried solid dispersion and heat-treated solid dispersion showed enhanced bioavailability, whereas mechanical mixture showed no improvement.

Animals↗
PubMed1998

Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form.

To enhance the dissolution rate and bioavailability of poorly water-soluble ketoprofen, a novel oral dosage form of ketoprofen, termed ketoprofen dry elixir, was developed by the spray-drying technique. Ketoprofen, dextrin, and sodium lauryl sulfate were dissolved in an ethanol-water mixture (20:25 w/w) and thereafter spray-dried to form the ketoprofen dry elixir. Comparative studies on the in vitro dissolution and in vivo adsorption of ketoprofen in the form of dry elixir and powder were carried out. Ketoprofen in the dry elixir completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved during 60 min. The initial dissolution rate of ketoprofen in the dry elixir markedly increased in distilled water at 37 degrees C, becoming fourfold higher than that of ketoprofen powder alone. The maximal plasma concentration of ketoprofen (Cmax) and the area under the concentration-time curve from zero to 8 hr (AUC0-8 hr) after the oral administration of dry elixir increased about 3.2- (24.6 versus 7.6 micrograms/ml) and 2.2-(38.4 versus 17.3 micrograms hr/ml) fold compared with powder alone. It was obvious that ketoprofen dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble ketoprofen.

Administration, Oral↗
PubMed1996

Preparing hydroxyapatite powders with controlled morphology.

We developed a synthesis method for hydroxyapatite particles with different morphologies. The process involved chemical precipitation and spray drying, which produced spherical, agglomerated hydroxyapatite granules with controlled particle sizes and structures. These granules contained nanoparticles with an average crystalline size of about 10 nm. We controlled the morphologies of the granules by adjusting the spray-drying conditions, such as the volume fraction of feed slurry and the atomization pressure. The spray-dried granules were doughnut shapes, solid spheres, or hollow spheres, and their sizes were controlled by varying the atomization pressure and the concentration of the feed slurry.

Adhesiveness↗
PubMed1998

Use of hydrophilic polymers with microcrystalline cellulose to improve extrusion-spheronization.

Microcrystalline cellulose 19 parts was combined with sodium carboxymethylcellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose or polyvinylpyrrolidone one part, either by spray-drying or physical mixing. This combined excipient (20%) mixed with lactose (80%) and water was added to aid formation of pellets by the process of extrusion-spheronization. Spray-dry combined excipient produced pellets with higher yield, better sphericity and improved tolerance to minor variation in the level of water added, compared with the physical mix excipient. Physicochemical testing based on scanning electron microscopy with energy dispersive analysis, differential scanning calorimetry and X-ray diffraction analysis, indicated that the spray-drying with the hydrophilic polymer caused disintegration of the microcrystalline cellulose component into smaller crystallites, favouring its more uniform dispersion throughout the lactose during subsequent processing. The hydroxypropyl cellulose or polyvinylpyrrolidone containing excipients were the most satisfactory of the hydrophilic polymers examined, because they had the least adhesive strength favouring maximum yield of highly spherical pellets.

Calorimetry, Differential Scanning↗