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A simple method for evaluating the mixing efficiency of a new type of pan coater.

The objective of this study was to investigate some important process parameters on the mixing behavior of a new coater type. The coater used in this study, the Bohle BLC pan coater, differs from other coaters in its high length to diameter ratio. The pan coater can be divided into two zones: drying and spraying zone. The temperature difference between two points in the pan (one in each zone) was used to explore the influence of some process parameters, i.e. the pan speed and the inclination of the rotation axis on the mixing behavior. In addition, the effect of the spray rate on the temperature difference was studied. The results of the current study demonstrated the possibility to characterize the mixing behavior in a pan coater by a simple temperature measurement. The temperature difference method resulted in a model, which was comparable to the model from a conventional mixture experiment. It was shown that the pan speed and the spray rate influenced the temperature difference and, consequently, the mixing efficiency. However, the inclination of the rotation axis did not show an important effect.

Drug Compounding↗

Influence of aqueous coatings on the stability of enteric coated pellets and tablets.

Pancreatin pellets, placebo pellets and tablets containing vitamin B2 were coated with various aqueous and organic enteric polymers, HPMCAS, HP, Eudragit L 100-55, Eudragit L 30 D-55, CAP, CAT, CMEC and PVAP, comparatively investigated and tested for storage stability. With the exception of Eudragit L 100-55 and Eudragit L 30 D-55, higher amounts of coating material were needed to achieve gastro-resistance with aqueous coating than with organic coating. Film formation from aqueous dispersions of micronized HP 55 was affected by the degree of micronization and was improved by reducing the particle size of the polymer. Undercoating was another suitable measure to decrease the amount of coating material required. The choice of plasticizer was of special importance in the aqueous dispersions, and type and quantity must be appropriate for the polymer applied. Non-polymeric plasticizers such as triethyl citrate (TEC) evaporated along with water during the spraying or drying process and high temperatures promoted such losses. The moisture-sensitive pancreatic enzymes were damaged both by humidity and heat during aqueous coating. The extent of damage was dependent on the coating equipment used. Upon storage, coatings obtained from aqueous dispersions showed changes in enteric performance or release characteristics as a consequence of three chemical/physical mechanisms: hydrolysis of ester linkages in the polymer or plasticizer, evaporation of the plasticizer, delayed film formation. The active ingredient pancreatin induced hydrolysis of the ester based film-former hydroxypropyl methylcellulose acetate succinate (HPMCAS). However, even without the influence of enzymes, the phthalic ester groups of aqueous hydroxypropyl methylcellulose phthalate (HP) were partly cleaved after 11 months storage. In HPMCAS-coated pancreatin pellets, the plasticizer glyceryl triacetate was almost completely hydrolyzed by the enzymes, whilst triethyl citrate was lost by evaporation through permeable packaging material at elevated temperatures. Open storage at elevated temperatures and humidities caused changes in the surface structure of HPMCAS coatings, consisting of a smoothing of the originally somewhat porous film and sticking. When applied to vitamin B2 tablets, Eudragit L 100-55, Opadry enteric (PVAP) and Aqoat (HPMCAS) proved to be quite stable aqueous enteric coatings, whereas cellulose acetate phthalate CAP or cellulose acetate trimellitate CAT coatings as ammonia-neutralized aqueous solution or as water-based pseudolatex Aquateric were unstable when stored under stress conditions.

Drug Implants↗

Nasal peak inspiratory flow through Turbuhaler in children with symptomatic rhinitis and in healthy children.

Topical treatment of allergic or vasomotor rhinitis is possible by means of pressurized metered dose inhalers, aqueous spray, or dry powder inhalers. In children, little is known about nasal drug delivery by dry powder inhalation. The airflow through the device is critical for the drug release and a sufficient nasal inspiratory flow is needed for intranasal drug delivery from a dry powder inhaler. In order to investigate from what age children with allergic or vasomotor rhinitis can reliably use such a device, device-dependent nasal peak inspiratory flow (DnPIF) was measured. The maximal DnPIF was measured in children aged 4-13 years making use of a dry powder inhaler (Turbuhaler) connected to a spirometer (Vitalograph). In the clinically relevant context, instructions from the doctor and one week's use of a Turbuhaler at home were found to be sufficient to obtain a good inhalation technique and were shown to improve DnPIF at least as effectively as visual feedback training at the clinic. Children with rhinitis, as well as healthy children from the age of 6 years, were able to generate a DnPIF sufficient to obtain a reliable nasal delivery of a dry powder drug dose. DnPIF values correlated with age. Consequently, a recommendation to use a nasal Turbuhaler from the age of 6 for topical drug delivery in the treatment of allergic or vasomotor rhinitis seems reasonable.

Administration, Inhalation↗

Airborne concentrations of benzene and mineral spirits (stoddard solvent) during cleaning of a locomotive generator and traction motor.

Mineral spirits (also called Stoddard solvent), a petroleum distillate, is often used as a degreaser or an industrial cleaning agent. Although several studies measured airborne concentrations of mineral spirits in various occupational settings, none have characterized the airborne concentrations of benzene from use of mineral spirits. Recent case reports have suggested that benzene, as a contaminant in mineral spirits, might be responsible for adverse health effects. Because some claims of health effects in the railroad industry have been attributed to potential historical exposures to mineral spirits and little information is available regarding air concentrations in this type of occupational setting, a simulation study was conducted to quantitate historical exposures a railroad worker might have experienced while spraying mineral spirits on locomotive engine parts in the 1970s. To quantitate potential historical exposures, worker tasks were simulated under worst-case exposure conditions by spraying minerals spirits on a locomotive generator and traction motor. The results of both generator and traction motor cleaning events produced concentrations of mineral spirits ranging from 34 to 221 ppm and an average 1-h concentration of 121 ppm, whereas benzene concentrations associated with the spraying and drying tasks were less than the limit of detection (0.002-0.006 ppm). Results indicate that a railroad worker who cleaned a locomotive traction motor and generator with mineral spirits for 2 h each workday under worst-case exposure conditions would be exposed to an 8-h time-weighted average (based on lapel measurements) of 30.4 ppm airborne mineral spirits. On the basis of the conditions under which these concentrations were obtained, the results should be the reasonable maximum values that can be achieved in a modern-era (post-1970) workplace in the United States.

Air Pollution, Indoor↗

Response of foodborne Salmonella spp. marker strains inoculated on egg shell surfaces to disinfectants in a commercial egg washer.

The objective of this study was to determine the effectiveness of an iodine based disinfectant (IBD, Iocide, Biomedical Development Corporation, San Antonio, TX) on Salmonella enteritidis and S. typhimurium inoculated on egg shell surfaces under simulated industry egg processing conditions with a commercial egg washer used as the sanitizer delivery system. Re-circulated egg washer water containing 1.40-2.85 g/l total dissolved solids was obtained from a commercial egg processing. Sanitizing treatments consisted of distilled deionized water (DDW), IBD, and chlorine (CL; 200 ppm). All treatments (DDW, IBD and CL) significantly (p < 0.05) decreased Salmonella spp. populations on the shell compared to dry (no spray) egg controls. However, efficacy of egg sanitizers appeared to be dependent on the level of total dissolved solids in the egg wash water.

Animals↗

[Influence of smear layer and adhesive resin on the retentive force of amalgam restoration in vitro study].

UNLABELLED: The purposes of this in vitro study were to determine whether removing of smear layer and using of self-cured adhesive can increase retentive strength of amalgam restoration and to understand the adhesive mechanism between amalgam and adhesive. Class I cavities without mechanical retention were prepared in the occlusal surfaces of 45 extracted molars which were randomly divided into 3 groups. Group 1: 10%EDTA(pH 7.4) was applied to cavity walls for 1 minute prior to amalgam condensation. Group 2: 10%EDTA was applied in the same manner as in group 1, then the walls were water-sprayed and dried. Miradapt adhesive was applied, and amalgam must be packed into cavity before the adhesive cures. CONTROL GROUP: no special treatment before amalgam condensation. The tensile strength of the restorations were measured. The adhesive interface of two samples from group 2 were evaluated by SEM and EDS. As a result, removing smear layer had little effect on retentive force of amalgam (P > 0.05), while removing smear layer and applying adhesive improved the retentive strength of amalgam fillings significantly (P < 0.05), and there were micromechanical interlock between amalgam and adhesive according to SEM and EDS observation.

Adhesives↗

Detection of alpha-methyldopa on thin-layer plates using pi-acceptors in 1,4-dioxane.

pi-Acceptors (P-chloranil and chloranilic acid) in 1,4-dioxane were used to detect alpha-methyldopa on thin layer plates. Thin layer plates coated to a thickness of 0.25 mm with silica gel G60 were spotted with solution of alpha-methyldopa from drug formulations and pure alpha-methyldopa solution. The plates were developed in a solvent system of methanol: glacial acetic acid: water (14:5:3). The developed plates were dried and sprayed with pi-acceptors, and further were counter-sprayed with dimethylformamide (DMF). P-Chloranil gave an immediate blue green complex with alpha-methyldopa which intensified on counter-sprayed with DMF. alpha-methyldopa (reference sample and those from drug formulations) gave Rf of 0.85 and excipients from the drug formulations did not interfere with the result.

Benzoquinones↗

A study of the effect of povidone-iodine on polymorphonuclear leucocyte chemotaxis.

Studies were made of the effect of povidone-iodine on polymorphonuclear leucocyte chemotaxis. Polymorphonuclear leucocytes were incubated with various concentrations of povidone-iodine and allowed to migrate across a membrane towards a chemotactic agent. Chemotactic movement was found to decrease as the concentration of povidone-iodine rose, 75 micrograms/ml completely inhibiting all movement. A concentration of 10 micrograms/ml of povidone-iodine was found actively to repel the white cells. In vivo studies in mice showed a reduction in polymorphonuclear leucocytes at wound surfaces in the presence of povidone-iodine dry powder spray.

Animals↗

[Determination of 3, 4-benzopyrene in spiruline algae produced and treated by various procedures].

Spirulina algae grow in highly salted natural lakes. Artificial cultivation in tanks with addition of carbon dioxide (natural gas, burned gases) has been studied in order to improve the biosynthesis. A possible 3, 4-benzopyrene (BaP) contamination must be then considered. Several BaP determinations have been performed in batches of algae from bath origins, prepared following different processes (filtration, spray, cylinder drying). BaP contents are very low (2 to 3 ppb) and comparable between batches.

Benzopyrenes↗

Effect of different cleaning regimens on recovery of Clostridium perfringens on poultry live haul containers.

Clostridium perfringens is important to both poultry producers and humans. The excretion rate of pathogenic foodborne bacteria increases after live haul; however, the majority of research into flock cross-contamination has been performed on Salmonella and Campylobacter. Research into the sources of C. perfringens in poultry operations have implied that dirty transport containers do harbor this organism and, therefore, can potentially contaminate subsequent flocks. The objectives of this study were to examine both small plastic crates and large dump coops to determine which cleaning regimens were most effective in reducing C. perfringens contamination. Additionally, 2 different holding periods for small crates were compared to determine whether holding time influences C. perfringens recovery before and after cleaning. Two experiments were performed. One involved small plastic crates; the other involved large dump coops. Four small crate cleaning and disinfection treatments consisted of pressure washing, pressure washing and sun-drying, pressure washing with a (5%, vol/vol) sodium hypochlorite dip, and pressure washing with a quaternary ammonium dip. The second experiment involved dump coops. The 5 dump coop cleaning and disinfection treatments consisted of pressure washing, pressure washing with a (5%, vol/vol) sodium hypochlorite spray, pressure washing with a quaternary ammonium spray, 48-h drying after the sodium hypochlorite spray, and 48-h drying after the quaternary ammonium spray. The recovery of C. perfringens from small and large dirty transport containers averaged 1.94 and 4.43 log10 cfu/mL, respectively. There was no significant difference in C. perfringens recovery based on holding time for small crates. With small crates, pressure washing provided a significant decrease in the amount of C. perfringens recovered. The greatest bacterial reduction in dump coops, 2 to 3 log10 cfu/mL, was observed after 48 h of drying. This information provides solutions to poultry operations to reduce the cross-contamination of this food safety pathogen via transport containers.

Animals↗

Heat strain attenuation while wearing NBC clothing: dry-ice vest compared to water spray.

BACKGROUND: While wearing impermeable nuclear, biological, and chemical (NBC) clothing, reduction of thermal stress is of primary importance. We compared the effect between two cooling methods on the attenuation of heat strain. METHODS: There were six male subjects who were divided into two groups of three and exposed on two consecutive days to 125 min of exercise in a high heat load (40 degrees C, 40% RH) wearing NBC clothing. They were cooled by one of two different cooling methods: an active cooling vest (CV) based on the sublimation of dry ice, or tap water spraying (TP). RESULTS: After 2 h, rectal temperature (Tre) was significantly higher for the CV compared with the TP (38.1 +/- 0.04 degrees C vs. 37.7 +/- 0.10 degrees C, respectively). Skin temperature (Tsk) was significantly higher for the CV compared with the TP (36.60 +/- 0.54 degrees C vs. 34.90 +/- 0.35 degrees C, respectively). In the second hour, heart rate (HR) was significantly higher for CV compared with TP (118 +/- 13 bpm vs. 104 +/- 64 bpm, respectively). Heat storage was significantly higher after the first and second hours for the CV compared with the TP. The physiological strain index (PSI) was higher for CV compared with TP in the second hour. Sweat rate (msw) was significantly higher for CV compared with TP (560 +/- 45 g x h(-1) vs. 409 +/- 84 g x h(-1), respectively). Subjective thermal comfort was not significantly different. CONCLUSIONS: TP was more effective than the CV in reducing heat strain under the conditions used in the study. Until a significant breakthrough in reducing heat strain while wearing NBC clothing in field conditions can be found, TP appears to be an effective and recommended cooling method.

Adult↗

Enhanced aqueous dissolution of a poorly water soluble drug by novel particle engineering technology: spray-freezing into liquid with atmospheric freeze-drying.

PURPOSE: The purpose of this work was to investigate spray-freezing into liquid (SFL) and atmospheric freeze-drying (ATMFD) as industrial processes for producing micronized SFL powders with enhanced aqueous dissolution. Micronized SFL powders dried by ATMFD were compared with vacuum freeze-dried SFL powders. METHOD: Danazol was formulated with polyvinyl alcohol (MW 22,000), polyvinylpyrrolidone K-15, and poloxamer 407 to produce micronized SFL powders that were freeze-dried under vacuum or dried by ATMFD. The powders were characterized using Karl-Fischer titration, gas chromatography, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, surface area, and dissolution testing (SLS 0.75%/Tris 1.21% buffer media). RESULTS: Micronized SFL powders containing amorphous drug were successfully dried using the ATMFD process. Micronized SFL powders contained less than 5% w/w and 50 ppm of residual water and organic solvent, respectively, which were similar to those contents detected in a co-ground physical mixture of similar composition. Micronized SFL powders dried by ATMFD had lower surface areas than powders produced by vacuum freeze-drying (5.7 vs. 8.9 m2/g) but significantly greater surface areas than the micronized bulk drug (0.5 m2/g) and co-ground physical mixture (1.9 m2/g). Rapid wetting and dissolution occurred when the SFL powders were introduced into the dissolution media. By 5 min, 100% dissolution of danazol from the ATMFD-micronized SFL powder had occurred, which was similar to the dissolution profile of the vacuum freeze-dried SFL powder. CONCLUSIONS: Vacuum freeze-drying is not a preferred technique in the pharmaceutical industry because of scalability and high-cost concerns. The ATMFD process enables commercialization of the SFL particle-engineering technology as a micronization method to enhance dissolution of hydrophobic drugs.

Calorimetry, Differential Scanning↗

Fixation techniques for fine needle aspiration biopsy smears prepared off site.

OBJECTIVE: To identify a simple, cost-effective, reliable fixation method for fine needle aspiration biopsy (FNAB) yielding a specimen suitable for mail transport. STUDY DESIGN: Smears prepared from 59 FNABs of surgical specimens were fixed by continuous fixation in 95% ethanol, spray fixation, air drying, ethanol fixation for either 5 minutes or 4 hours followed by spray fixation, or fixation in 95% ethanol for either 30 minutes or 4 hours followed by air drying. Fixation was graded as unsatisfactory, suboptimal, average, good or excellent. RESULTS: Of smears continuously fixed in ethanol, 96.6% were graded as excellent. Of smears fixed in ethanol followed by spray fixation, 93.2% were excellent irrespective of fixation time; 64.4% of spray-fixed smears were excellent and 27.1% good. Of air dried smears, 93.2% were unsatisfactory or suboptimal; 83.0% of smears fixed in ethanol for 30 minutes and 74.6% of smears fixed for 4 hours prior to air drying were unsatisfactory or suboptimal. CONCLUSION: Fixation of smears in 95% ethanol followed by spray fixation produces excellent results, comparable to those with continuous fixation in ethanol. Spray fixation is generally good but not consistently excellent. Air drying or fixation in ethanol followed by air drying yields unsatisfactory or suboptimal results in most cases.

Biopsy, Needle↗

A comparison of budesonide nasal dry powder with fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis.

There is circumstantial evidence that the incidence of allergic rhinitis is becoming increasingly common. There may also be a need for more potent drugs with minimal local and systemic side effects. This study has compared the efficacy and safety of budesonide delivered as nasal dry powder with fluticasone propionate aqueous nasal spray in the treatment of perennial allergic rhinitis. Ninety-eight patients participated in a randomized, parallel group and partly blinded study. Treatment consisted of budesonide dry powder (Rhinocort Turbuhaler) at once daily doses of 200 micrograms (n = 24) or 400 micrograms (n = 22), fluticasone propionate (200 micrograms) once daily (n = 25), and placebo for budesonide dry powder (n = 27). A six-week treatment period was preceded by a two-week baseline period without treatment. Efficacy was assessed by daily subjective scoring of nasal symptoms. Safety was assessed by rhinoscopy, analysis of urine cortisol, and questioning of adverse events. All active treatments were significantly superior to placebo in controlling nasal symptoms. No significant differences in efficacy were found between the two budesonide regimens and fluticasone propionate. Adverse events were few and minor, and non-significantly distributed between treatments. In conclusion, this study shows that budesonide dry powder administered from Turbuhaler (200 or 400 micrograms) and fluticasone propionate aqueous spray (200 micrograms) administered in once daily doses, are effective and safe treatments of perennial allergic rhinitis. These novel treatments may enhance the current available alternatives in clinical practice.

Administration, Topical↗

Stabilization and encapsulation of human immunoglobulin G into biodegradable microspheres.

The instability of protein during preparation, storage, and release has become a major concern in recent years in the encapsulation of proteins into biodegradable polymers for controlled release systems. The present investigation was performed to study the mechanism of degradation of human immunoglobulin G (IgG) in double emulsion and solid-in-oil-in-water (S/O/W) encapsulation processes. The stabilizing effects of various excipients during the period of protein atomization using spray freeze-drying and subsequent encapsulation into polylactide-co-glycolide (PLGA) microspheres were explored. The size-exclusion high-performance liquid chromatography (SEC-HPLC) results showed that ultrasonication did not change the primary structure of IgG significantly. However, enzyme-linked immunosorbent assay (ELISA) revealed that the subsequent double-emulsion solvent evaporation process denatured nearly 80% of the total amount of IgG. This was possibly due to the adsorption, unfolding, and aggregation of IgG at the water/organic solvent interface. Both mannitol and trehalose could stabilize IgG during spray freeze-drying, with over 90% retention of its molecular integrity and immunoactivity, which were verified using SEC-HPLC and ELISA. Solid protein microparticles were further entrapped into monolithic-type microspheres of PLGA using the S/O/W method. FTIR results suggested that the incomplete release that is often observed in the formulation of controlled protein release systems may be due to the degradation or aggregation of protein in the solid polymer matrix.

Biodegradation, Environmental↗

Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Administration, Intranasal↗