A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device. This review focuses on the DPI formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency. Advances in understanding of aerosol and solid state physics and interfacial chemistry are moving formulation development from an empirical activity to a fundamental scientific foundation.

http://rc.rcjournal.com/content/respcare/50/9/1209.full.pdf

Dry powder inhaler formulation.

Inner-city children have high rates of asthma. Exposures to particles, including allergens, may cause or exacerbate asthma symptoms. As part of an epidemiologic study of inner-city children with asthma, continuous (10-min average) measurements of particle concentrations were made for 2-week periods in 294 homes drawn from seven cities. Measurements were made using an optical scattering device that is most sensitive to fine particles. The concentrations recorded by these devices were corrected to agree with colocated outdoor gravimetric PM2.5 monitors. Indoor concentrations in the homes averaged 27.7 (standard deviation = 35.9) micro g/m3, compared with concurrent outdoor concentrations of 13.6 (7.5) micro g/m3. A multivariate model indicated that outdoor particles penetrated indoors with an efficiency of 0.48 and were therefore responsible for only 25% of the mean indoor concentration. The major indoor source was smoking, which elevated indoor concentrations by 37 micro g/m3 in the 101 homes with smokers. Other significant sources included frying, smoky cooking events, use of incense, and apartment housing, although the increases due to these events ranged only from 3 to 6 micro g/m3. The 10-min averaging time allowed calculation of an average diurnal variation, showing large increases in the evening due to smoking and smaller increases at meal times due to cooking. Most of the observed variance in indoor concentrations was day to day, with roughly similar contributions to the variance from visit to visit and home to home within a city and only a small contribution made by variance among cities. The small variation among cities and the similarity across cities of the observed indoor air particle distributions suggest that sources of indoor concentrations do not vary considerably from one city to the next, and thus that simple models can predict indoor air concentrations in cities having only outdoor measurements.

Particle concentrations in inner-city homes of children with asthma: the effect of smoking, cooking, and outdoor pollution

Toxic emissions from open burning.

DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at: Toxicological Profiles are a unique compilation of toxicological information on a given hazardous substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation of available toxicologic and epidemiologic information on a substance. Health care providers treating patients potentially exposed to hazardous substances will find the following information helpful for fast answers to often-asked questions. Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating patients about possible exposure to a hazardous substance. It explains a substance's relevant toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of the general health effects observed following exposure. Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are reported in this section. NOTE: Not all health effects reported in this section are necessarily observed in the clinical setting. Please refer to the Public Health Statement to identify general health effects observed following exposure. The following additional material can be ordered through the ATSDR Information Center: Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an exposure history and how to conduct one are described, and an example of a thorough exposure history is provided. Other case studies of interest include Reproductive and Developmental Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide Toxicity; and numerous chemical-specific case studies. viii Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene (prehospital) and hospital medical management of patients exposed during a hazardous materials incident. Volumes I and II are planning guides to assist first responders and hospital emergency department personnel in planning for incidents that involve hazardous materials. Volume III— Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care professionals treating patients exposed to hazardous materials. Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. Other Agencies and Organizations The National Center for Environmental …

/pdf/toxicological-profile-for-fluorides-hydrogen-fluoride-and-rydm3hr31p.pdf

Toxicological profile for fluorides, hydrogen fluoride, and fluorine

In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home.

/pdf/incense-smoke-clinical-structural-and-molecular-effects-on-5c70akol6l.pdf

Incense smoke: clinical, structural and molecular effects on airway disease

Characterization of emissions from burning incense

Lead in candle emissions

Rates of polycyclic aromatic hydrocarbon emissions from incense.

As an odorless, nontoxic, and inert compound, sulfur hexafluoride (SF6) is one of the most widely used tracer gases in indoor air quality studies in both controlled and uncontrolled environments. This compound may be subject to reactions with water vapor under elevated temperature to form acidic inorganic compounds such as HF and H2SO4. Thus, in the presence of unvented combustion sources such as kerosene heaters, natural gas heaters, gas log fireplaces, candles, and lamps, the SF6 dissociation may interfere with measurements of the emissions from these sources. Tests were conducted in a research house with a vent-free natural gas heater to investigate these potential interferences. It was observed that the heater operation caused about a 5% reduction of SF6 concentration, which can be an error source for the ventilation rate measurement and consequently the estimated pollutant emission rates. Further analysis indicates that this error can be much greater than the observed 5% under certain test conditions because it is a function of the ventilation flow rate. Reducing the tracer gas concentration has no effect on this error. A simple theoretical model is proposed to estimate the magnitude of this error. The second type of interference comes from the primary and secondary products of the SF6 dissociation, mainly H2SO4, SO2, HF, and fine particulate matter (PM). In the presence of approximately 5 ppm SF6, the total airborne concentrations of these species increased by a factor of 4-10. The tests were performed at relatively high SF6 concentrations, which is necessary to determine the interferences quantitatively. The second type of interference can be significantly reduced if the SF6 concentration is kept at a low ppb level.

Jenia A McBrian

Papers

Characterization of emissions from burning incense

Lead in candle emissions

Rates of polycyclic aromatic hydrocarbon emissions from incense.

Dissociation of sulfur hexafluoride tracer gas in the presence of an indoor combustion source.