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The efficacy of Polysporin First Aid Antibiotic Spray (polymyxin B sulfate and bacitracin zinc) against clinical burn wound isolates.

Polysporin First Aid Antibiotic Spray (Burroughs Wellcome Co., Research Triangle Park, N.C.) is a dry spray containing 200,000 units Aerosporin (polymyxin B sulfate) and 10,000 units bacitracin zinc, along with a propellant. Each 1-second spray delivers approximately 2300 units of polymyxin B sulfate and 115 units of bacitracin zinc. This study was designed to evaluate the efficacy of Polysporin Spray against various clinical isolates. Blood agar plates were inoculated with a pure culture of each isolate. Polysporin was then sprayed in an area approximately 30 mm in diameter. The area of inhibition was measured and recorded after 18 to 24 hours of incubation. A clear zone at least 20 mm in diameter with surrounding edges of growth indicated sensitivity. A zone less than 20 mm in diameter or growth over the whole plate indicated resistance. Three hundred fifty-three clinical isolates (202 gram positive and 151 gram negative) were tested. The results show that Polysporin inhibits the growth of all the gram-positive organisms, including methicillin-resistant strains of Staphylococcus. The gram-negative organisms were also sensitive to Polysporin Spray, with the exception of Serratia marcescens, Morganella morganii, and Proteus mirabilis. This study suggests that Polysporin First Aid Antibiotic Spray may be effective for wounds contaminated with gram-positive and some gram-negative organisms.

Administration, Topical↗

[Technology for tablets with herbal extracts and evaluation of its quality].

The article deals with the development of technology for production of tablets containing dry herbal extracts. Dry herbal extracts of two different compositions were produced by spray drying using BUCHI 190 apparatus. The quality of dry extracts was evaluated by determination the loss of extract mass during the drying process, and estimation of the amount of biologically active combinations. The tableting methods for dry herbal extracts--direct compression and also employing granulation--were used. The quality of the produced tablets was determined by examining their appearance, resistance to abrasion, crushing strength, mass uniformity, disintegration time. Contents of biologically active compounds in tablets were evaluated by the quantitative methods.

Plant Extracts↗

Calcining influence on the powder properties of hydroxyapatite.

The effect of different calcination temperatures on the powder characteristics and the sintered density of synthetic hydroxyapatite (HA) powders, produced using two different processing routes, was examined. Powders were produced by either drying, milling and sieving an as-precipitated HA or by spray-drying a slurry of precipitated HA. Calcining the two powders at temperatures between 400 and 1000 degrees C did not significantly affect the powder particle size. The specific surface areas of the two powders, however, were reduced from 70-80 m2/g for a calcination temperature of 400 degrees C to approximately 5-7 m2/g for 1000 degrees C. Analysis of the surfaces of the HA powders using scanning electron microscopy (SEM) illustrated the coarsening and subsequent sintering of the sub-micron crystallites that constitute a powder particle as the calcination temperature increased, corresponding to the decrease in surface area of the powders. The sintered densities of the final ceramics were not significantly affected by calcining the powders. Microhardness measurements of ceramics prepared from powders calcined at different temperatures showed no significant variations with calcination temperature or powder processing method. The results of this study have illustrated that for applications where HA may be used in powder form, for example in plasma-spraying and for the production of HA-polymer composites, calcining the HA will significantly affect the powder properties, namely the surface area and morphology of the powders. For applications requiring HA in a dense ceramic form, for example as granules or blocks, calcining the powders does not significantly affect the properties of the final ceramic.

Journal Article↗

Dry-powder inhalers: evaluation of testing methodology and effect of inhaler design.

We have previously developed a spray dried formulation of a model protein (beta-galactosidase) of a size suitable for evaluation in dry powder inhaler devices. In this study, we wished to evaluate the roles of various methods available for the laboratory testing of dry powders for inhalation (cascade impactor, twin impinger, aerodynamic time of flight and image analysis). Secondly we wished to compare different inhaler devices using formulations with and without a carrier. Both the cascade impactor and twin impinger were appropriate methods for the testing of dry powder inhalers, and gave comparable estimates of respirable fraction. Image analysis and aerodynamic time of flight were suitable methods for determining the particle size of the dry powders, although the former was considerably more time consuming than the latter. The four inhalers evaluated differed greatly in terms of in vitro deposition properties. The presence of a carrier significantly improved respirable fraction with the poorer inhalers, but was less critical to the performance of the more efficient devices.

Equipment Design↗

Investigation of the stabilisation of freeze-dried lysozyme and the physical properties of the formulations.

The long-term stability of a protein formulation requires that the glass transition temperature (Tg) of the formulation should be maximised and the perturbation of the protein native structure in the dried form after processing minimised. In the present study, the stabilisation of lysozyme structure conferred by excipients was monitored using second derivative Fourier transform infrared spectroscopy and the physical properties of protein formulations were investigated using differential scanning calorimetry. The results showed that the preservation of protein native structure during freeze-drying and the Tg of freeze-dried formulations were excipient- and excipient to enzyme mass ratio-dependent. The freeze-dried lysozyme appeared to be less effectively stabilised compared with the spray-dried enzyme when the excipients and the excipient to enzyme mass ratios were the same. In terms of the preservation of the secondary structure of lysozyme, glycerol and sucrose seemed to be more efficient than trehalose, although the Tg of trehalose-containing formulations were found to be higher than the Tg of the equivalent sucrose-based ones. With adding either trehalose or dextran to sucrose-containing formulations, the stabilisation of lysozyme native structure could be as effective as with sucrose alone, whilst the Tg could be enhanced. The results in this study suggested that lysozyme, processed by freeze-drying, is stabilised primarily by the water substitution mechanism.

Chemistry, Pharmaceutical↗

Copper bioavailability in pork liver and in various animal by-products as determined by chick bioassay.

Three chick experiments were conducted to investigate possible explanations for why pork liver provides no bioavailable Cu to chicks. Autoclaving, acid-hydrolysis, and protease-digestion increased (P < .01) Cu bioavailability in pork liver to 32, 46, and 63%, respectively, from virtually 0% of the Cu in unprocessed pork liver (relative to CuSO4, which was set at 100%). Addition of EDTA at 200 mg/kg to the diet containing 1 mg of Cu/kg from unprocessed pork liver also resulted in an increased (P < .07) Cu bioavailability, to 23%. Tissues representing different sources of endogenous Cu in the pig also were evaluated for their Cu bioefficacy. Freeze-dried (FD) porcine bile did not have any bioavailable Cu, whereas spray-dried porcine plasma contained Cu that was as available (99%) as that in CuSO4. In addition, when FD pork liver or FD porcine bile was added to the basal diet containing .5 mg of Cu/kg from CuSO4, Cu bioavailability in CuSO4 was reduced (P < .05) to 34% and 19%, respectively, of values obtained with CuSO4 alone. An additional experiment was conducted to estimate Cu bioefficacy in selected animal-source feed ingredients. Copper bioavailability in all-beef meat and bone meal, all-pork meat and bone meal, mixed-species meat and bone meal, high-bone meat and bone meal, poultry byproduct meal, and hog hair meal was 4, 53, 28, 8, 42, and 9%, respectively, relative to CuSO4. Feather meal did not provide any bioavailable Cu to chicks.

Animal Feed↗

Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats.

A dry powder aerosol formed of human growth hormone (hGH), lactose and dipalmitoylphosphatidylcholine was assessed for systemic delivery of the hormone in rats. The fate of the protein locally in the deep lung was examined post-delivery. The powder was prepared by spray-drying and presented a primary particle diameter of 4.4 microm and a tap density of 0.069 g/cm(3). The mass median aerodynamic diameter was 4.4 micron in the multi-stage liquid impinger at 60 l/min using a Spinhaler device. The emitted dose and fine particle fraction were 89% and 58%, respectively. Varying the airflow rate from 30 to 90 l/min had limited impact on aerosolization properties in vitro. No hGH dimers or glycation adducts were produced during formulation of the powder. hGH absorbed into the bloodstream with a time to peak of 23 and 52 min and with an absolute bioavailability of 23% and 8% following intratracheal insufflation of the dry powder and intratracheal spray-instillation of a solution of the hormone, respectively. Confocal imaging of rat lung revealed an intense uptake of fluorescein isothiocyanate (FITC)-hGH by alveolar macrophages as early as 1 h post-delivery. A dry powder aerosol made of selected GRAS excipients improved absorption of hGH from the lung over a simple solution.

Administration, Inhalation↗

Effect of dry heating on the microbiological quality, functional properties, and natural bacteriostatic ability of egg white after reconstitution.

Spray-dried egg white (powder) is widely used in the food industry because of its variety of functional properties and its practical advantages. Moreover, egg white powder is generally considered safe because it can withstand high temperatures that allow for the destruction of all pathogens, especially Salmonella. In France, two types of treatments are used to improve the functional properties (whipping and gelling) of dried egg white: standard storage at 67 degrees C for about 15 days and storage at 75 to 80 degrees C for 15 days. The objective of this study was to investigate the effects of two dry-heating treatments (storage at 67 and 75 degrees C for 15 days) on the subsequent ability of egg white to resist Salmonella growth after reconstitution. The impact on the endogenous microflora of the powder and on its functional properties was also considered. Both dry-heating treatments were efficient in destroying a large number of Salmonella. Dry heating at 75 degrees C affected the bacteriostatic ability of reconstituted egg white to a greater extent than did dry heating at 67 degrees C. This loss of bacteriostatic ability could be attributable to the thermal denaturation of ovotransferrin, resulting in a reduction in its activity as an iron chelator. However, dry heating at 75 degrees C resulted in improved functional properties. Ultimately, no complete compromise between better functional quality and the preservation of the bacteriostatic ability of egg white after reconstitution is possible. Our results underline the importance of the use of hygienic conditions with egg white powder, especially with powder subjected to high-temperature treatments.

Consumer Product Safety↗

A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethylcellulose phthalate nanospheres.

PURPOSE: A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro. METHODS: Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air. RESULTS: Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surface-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air. CONCLUSIONS: Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.

Administration, Inhalation↗

Effects of substituting deproteinized whey and(or) crystalline lactose for dried whey on weanling pig performance.

We conducted two trials to determine the effects of replacing the lactose provided by spray-dried, edible-grade whey with edible-grade deproteinized whey or crystalline lactose on pig performance. In Exp. 1, 180 weanling pigs (initially 4.1 kg and 22 +/- 4 d of age) were allotted randomly to dietary treatments containing 18% lactose supplied by 1) 25% dried whey, 2) 12.5% dried whey and 9% crystalline lactose, 3) 18% crystalline lactose, 4) 12.5% dried whey and 10.9% deproteinized whey, or 5) 21.7% deproteinized whey. Casein was used to replace the lysine provided by dried whey in diets containing lactose and deproteinized whey. From d 0 to 14 after weaning, no differences (P > .10) were observed in ADG or ADFI. Pigs fed diets containing 18% crystalline lactose or 21% deproteinized whey had a higher (P < .05) gain:feed ratio (G/F) than did pigs fed diets containing 25% dried whey or 12.5% dried whey and 9% lactose. In addition, pigs fed diets containing 21% deproteinized whey had increased G/F compared to pigs fed the diet containing 10.9% deproteinized whey and 12.5% dried whey. In Exp. 2, 344 pigs (initially 4.4 kg and 14 +/- 2 d of age) were fed dietary treatments based on four sources of crystalline lactose replacing the lactose provided by dried whey in the positive control diet (20% dried whey). In addition, a negative control diet was formulated with 7.2% crystalline lactose. Casein was used to replace the lysine provided by dried whey. From d 0 to 14 after weaning, no differences (P > . 10) were observed in performance. However, pigs initially fed the positive control diet subsequently (d 14 to 28) consumed more feed than pigs fed the negative control diet. These results indicate that edible-grade deproteinized whey and crystalline lactose can replace the lactose provided by high-quality dried whey without affecting pig performance.

Aging↗

Description and preliminary evaluation of a new ultrasonic atomizer for spray-congealing processes.

A new atomizer that operates with ultrasonic energy is described. This apparatus is intended to obtain microparticulate drug delivery systems through spray-congealing or spray-drying technologies. In this work, some experimental results are reported on model systems submitted to spray-congealing. The formulations under examination contained theophylline and fenbufen as model drugs and stearic acid, carnauba wax, Cutina HR(R) and Compritol 888 ATO(R) as low melting excipients. Non-aggregate and spherical-shaped microparticles were obtained with all the materials tested; moreover, they had smooth surface and good flowability. The particle sizes depend on the amount of drug present and in each case the maximum size value of the distribution frequency was found to be 375 mu. In vitro release of the drug depends on its solubility and on the excipient lipophilicity. The results suggest that the ultrasound-assisted atomizer could be proposed as a possible alternative to traditional atomizers used for spray-congealing in the pharmaceutical field.

Chemistry, Pharmaceutical↗

Effects of pelleting and pellet conditioning temperatures on weanling pig performance.

We conducted two experiments to study the effects of pelleting and pellet conditioning temperature on weanling pig performance. In Exp. 1, 252 weanling pigs (PIC, L326 x C22) averaging 6.0 +/- 1.3 kg and 21 +/- 3 d of age were used to evaluate six corn-soybean meal-based diets containing 15% dried whey and formulated to contain 1.4% lysine. Treatments consisted of a control diet without spray-dried animal protein (SDAP) fed in meal form, a diet with 5% SDAP fed in meal form, and four diets with 5% SDAP that were conditioned at 60, 66, 71, or 77 degrees C for 10 s prior to pelleting. Pellets had a 3.97-mm diameter. The experimental diets were fed from d 0 to 14 after weaning, and all pigs were fed a common diet in meal form from d 14 to 28 after weaning. From d 0 to 7 after weaning, pigs fed diets containing SDAP had greater ADG, gain/feed (P < 0.001), and ADFI (P < 0.05) than pigs fed the control diet. No differences (P > 0.10) were observed between pigs fed the pelleted diets and those fed the SDAP diet in meal form. Conditioning temperature had no effect (P > 0.10) on weanling pig performance from d 0 to 14, and the diet fed from d 0 to 14 had no effect on overall performance (d 0 to 28). In Exp. 2, 252 weanling pigs (6.3 +/- 1.5 kg and 22 +/- 4 d of age) were used to evaluate diets with same composition as in Exp. 1, but treatments consisted of diets with or without SDAP conditioned at 60 degrees C before pelleting, and four diets containing 5% SDAP that were conditioned at 68, 77, 85, and 93 degrees C before pelleting. As in Exp. 1, conditioning lasted 10 s, pellets were 3.97 in mm diameter, and experimental diets were fed for the first 14 d of the 28-d experiment. From d 0 to 7, pigs fed the SDAP diet conditioned at 60 degrees C had greater ADFI (P < 0.05) and tended (P = 0.12) to have greater ADG than pigs fed the diet without SDAP and conditioned at 60 degrees C. From d 0 to 7, ADG (quadratic effect, P < 0.03) and ADFI (linear effect, P < 0.002) decreased as conditioning temperature increased, with the largest decrease observed above 77 degrees C. From d 0 to 14 and 0 to 28, ADG was not affected (P > 0.10) by pellet conditioning temperature or SDAP fed from d 0 to 14. The results of these studies suggest that conditioning diets containing 5% SDAP at temperatures above 77 degrees C decreases weanling pig growth performance.

Animal Feed↗

Availability to chicks of biotin from dried egg products.

Two feeding experiments were conducted with duplicate groups of five chicks each to study the availability of biotin in spray-dried egg products. In the first experiment chicks that were fed diets containing 43% dried whole egg (DWE) grew poorly and developed perosis and dermatitis. The signs were prevented and growth improved progressively with supplementation of 0.5 and 1.0 mg biotin/kg diet. In the second experiment dried egg yolk (DEY) and dried egg white (DEW) were compared with DWE at equivalent levels of egg components. Signs of biotin deficiency and reduced growth were slightly more severe with DEW than with DWE, although liver biotin content was slightly lower at 0 and 0.5 mg biotin/kg with DWE than with DEW. Growth with DEY and no added biotin was not different from that with DEY and 500 or 1000 mg biotin/kg diet, although liver biotin was lower than when supplemental biotin was added. Liver fat was approximately five times greater in the groups receiving DWE and DEY than in the groups receiving DEW. The results show that the biotin contained in egg yolk is inadequate to counteract the deficiency of biotin caused by the avidin in egg white so that unheated dried whole egg is deficient in this vitamin.

Animals↗

Formulation and characterization of lipid-coated tobramycin particles for dry powder inhalation.

PURPOSE: This study was conducted to develop and evaluate the physicochemical and aerodynamic characteristics of lipid-coated dry powder formulations presenting particularly high lung deposition. METHODS: Lipid-coated particles were prepared by spray-drying suspensions with different concentrations of tobramycin and lipids. The solid-state properties of the formulations, including particle size and morphology, were assessed by scanning electron microscopy and laser diffraction. Aerosol performance was studied by dispersing the powders into a Multistage Liquid Impinger and determining drug deposition by high-performance liquid chromatography. RESULTS: Particle size distributions of the formulations were unimodal, narrow with more than 90% of the particles having a diameter of less than 2.8 microm. All powder formulations exhibited mass median diameters of less than 1.3 and 3.2 microm, as determined by two different laser diffraction methods, the Malvern's Mastersizer and Spraytec, respectively. The fine particle fraction varied within a range of 50.5 and 68.3%. CONCLUSIONS: Lipid coating of tobramycin formulations resulted in a reduced agglomeration tendency and in high fine particle fraction values, thus improving drug deposition. The very low excipients content (about 5% m/m) of these formulations offers the benefit of delivering particularly huge concentrations of antibiotic directly to the site of infection, while minimizing systemic exposure, and may provide a valuable alternative treatment of cystic fibrosis.

Administration, Inhalation↗

Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder.

PURPOSE: To assess the pulmonary deposition and pharmacokinetics of an engineered PulmoSphere powder relative to standard micronized drug when delivered from passive dry powder inhalers (DPIs). METHODS: Budesonide PulmoSphere (PSbud) powder was manufactured using an emulsion-based spray-drying process. Eight healthy subjects completed 3 treatments in crossover fashion: 370 microg budesonide PulmoSphere inhaled from Eclipse DPI at target PIF of 25 L x min(-1) (PSbud25), and 50 L x min(-1) (PSbud50), and 800 microg of pelletized budesonide from Pulmicort Turbuhaler at 60 L x min(-1)(THbud60). PSbud powder was radiolabeled with 99mTc and lung deposition determined scintigraphically. Plasma budesonide concentrations were measured for 12 h after inhalation. RESULTS: Pulmonary deposition (mean +/- sd) of PSbud was 57+/-7% and 58+/-8% of the nominal dose at 25 and 50 L x min(-1), respectively. Mean peak plasma budesonide levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng x ml(-1) (THbud60). Median t(max) was 5 min after both PSbud inhalations compared to 20 min for Turbuhaler (P < 0.05). Mean AUCs were comparable after all inhalations, 5.1 (PSbud25), 5.9 (PSbud50), and 6.0 (THbud60) ng x h x ml(-1). The engineered PSbud powder delivered at both flow rates from the Eclipse DPI was twice as efficiently deposited as pelletized budesonide delivered at 60 L x min(-1) from the Turbuhaler. Intersubject variability was also dramatically decreased for PSbud relative to THbud. CONCLUSION: Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs.

Administration, Inhalation↗

Feeding lactose-intolerant children with a powdered fermented milk.

Fresh yogurt has been proposed as a milk substitute for lactase-deficient patients. We investigated the possibility that a dried, low-fat milk fermented by yogurt microorganisms would be effective. Processing of a fermented milk by spray-drying led to a powder with persistence of lactase activity (11.7 units/g) without storage at 4 degrees C and stable at room temperature (20-23 degrees C). The tolerance and absorption of 10.5 g of lactose in a volume of 150 ml was studied in 25 Gabonese lactase-deficient children aged 5-14 years in the form of a standard humanized milk formula followed 1 week later by the powdered fermented milk formula. Results of the breath hydrogen test showed that in 24 of 25 cases, lactose absorption was normal with a maximal rise of hydrogen over baseline of under 13 ppm after ingestion of the powdered fermented milk. The rise was above 20 ppm in the 25 children with the same load of lactose in the form of the standard formula and one-third had symptoms of lactose intolerance. This powdered fermented milk preparation should be considered as a valid approach in programs of nutritional support targeted to countries with a high prevalence of lactase deficiency.

Adolescent↗

Nasal distribution of radioactive drug administered using two dosage forms.

The deposition patterns of 99mtechnetium labelled disodium cromoglycate particles administered either from a metered dose aerosol with a conventional nasal adaptor or from a dry powder nasal inhaler were studied using gamma camera. Disodium cromoglycate particles were firstly labelled with 99mTc using the spray drying technique. Both the metered dose aerosol and the dry powder dosage form were formulated using these radioactive drug particles. Seven healthy volunteers inhaled either three aerosol doses or one dry powder dose unit into one nostril. The drug dose reaching nasal cavity after administration from these two dosage forms was about the same. The deposition patterns as well as the changes in distribution due to the mucociliary transport were monitored by a gamma camera equipped with a low energy all purpose collimator. Initially drug doses deposited in a wider area of the nasal cavity when disodium cromoglycate particles were administered as a dry powder dosage form. In addition, retention index (%) which illustrates the movements of drug particles by mucociliary transport from the initial area of application seemed to be slightly higher for a metered dose aerosol than for a dry powder dosage form. At the end of the 30 minutes measuring period the area of the mucosal layer covered by radioactive drug particles was clearly wider for the dry powder dosage form than for the metered dose aerosol. Thus it is well possible to administer drug particles effectively into the nasal cavity as a dry powder dosage form.

Administration, Inhalation↗

[In vitro evaluation of allergenicity of dried food powders manufactured for food provocation test].

Food provocation test (FPT) is one of important diagnostic methods for food allergy, but no standard antigens for FPT have yet been developed. In this study, dried powders were manufactured from five kinds of foods (cow's milk, hen egg, chicken, soybean and wheat) by spray-drying or freeze-drying and examined in vitro for their usefulness as antigens for FPT. In SDS-PAGE, the migration pattern of the extract from each powder was the same as or closely similar to that of the extract from its material. When analyzed by ELISA, a good correlation (r=0.853-0.978) in the reactivity with sera from food-allergic patients was observed between the extracts from each powder and its material. Moreover, in cow's milk, hen egg and soybean, almost the same ELISA inhibition curves were drawn, regardless of whether the extracts from each powder and its material were used as immobilized antigens or inhibitors. These results demonstrated that each powder contains the same allergens as its material at almost the same levels, being useful as an antigen for FPT. Favorably, the powders were found to be stored without significant changes in IgE reactivity at -20 degrees C or 5 degrees C for more than 18 months, although their storage at room temperature was suggested to be avoided.

Allergens↗