Aerosol formulations

Considerable developmental effort is being devoted to aerosol formulations using the compressed gases given in Table 4. These propellants are used in some food and industrial aerosols. Carbon dioxide and nitrous oxide, which tend to be more soluble, are often preferred. When some of the compressed gas dissolves in the product concentrate, there is partial replenishment of the headspace as the gas is expelled. Hence, the greater the gas solubiUty, the more gas is available to maintain the initial conditions. 

Over 68 aerosol products containing isopropyl alcohol solvent have been reported (145). Aerosol formulations include hair sprays (146), floor detergents (147), shoe poHshes (148), insecticides (149,150), bum ointments (151), window cleaners, waxes and poHshes, paints, automotive products (eg, windshield deicer), insect repellents, flea and tick spray, air refreshers, disinfectants, veterinary wound and pinkeye spray, first-aid spray, foot fungicide, and fabric-wrinMe remover (152) (see Aerosols). 

The opportunity of application of filters, solid sorbents and absorbing solutions has been investigated for synthetic pyrethroids concentrating from air. Silicagel KSK and polysorb are provided quantitative sorbption and desorbption pyrethroids. In case of aerosol formulations application of paper filters is possible. 

Focusing on furan ring compounds, Katsuda [28] developed furamethrin (18) in 1966, which was suitable as an active ingredient of electric vaporizing insecticides due to its extremely low toxicity to mammals and its high volatility. Almost simultaneously, resmethrin (19) was reported by Elliott et al. [29] in 1967 as possessing a powerful lethal effect, and has been used in aerosol formulations. 

On the other hand, heating is needed for volatilization of allethrin, prallethrin, phenothrin, permethrin, and others. In the case of aerosol formulations, the energy from a liquefied gas or compressed gas encourages volatilization. 

An aerosol formulation of the insect growth regulator hydroprene (Gen-trol) was labeled several years ago for use in the United States. There are no research reports with hydroprene aerosol, except for Bell and Edwards (1998), which describe a study conducted in Great Britain. In this study, aerosol applications of hydroprene (Protrol) prevented the development of eggs of the red flour beetle, T. castaneum, the confused flour beetle, T. confusum, and the almond moth, C. cautella, that had been placed in exposed dishes with food media. 

The second part describes different experimental approaches to simultaneously assess deposition and subsequent absorption of pharmaceutical aerosol formulations, typically by adapting some existing impactor/impinger devices to accommodate pulmonary epithelial cell culture systems. Differences between longtime and low-dose aerosol deposition in environmental toxicology and short time bolus inhalation of pharmaceutical aerosols are elucidated. 

An ideal in vitro model for the characterization of aerosol formulations would incorporate cell types from various regions of the lung (tracheal, bronchial, and alveolar) and would facilitate simulation of deposition mechanisms by impaction, sedimentation, and diffusion of a high-metered singlebolus inhalation. In the future, such systems may reduce the need for animal studies and may offer to correlate in a predictive way the results from such in vitro tests to clinical bioavailability data after pulmonary drug delivery in vivo. 

Bell, J.H., Fisons Patent, Pelletised medieament formulations. Application no. 152047 (1975). Vidgren, M.T., Vidgren, P.A., and Paronen, T.P., Int. J. Pharm., 35 139-144 (1987). Chawla, A., Spray-dried Powders for Use in Dry Powder Aerosol Formulation, PhD Thesis, University of London, 1993. 

Uses Organic synthesis vapor degreasing and cold cleaning solvent for fabricated metal parts textile processing aerosol propellants synthesis of fluoropolymers production of various coatings and inks may be ingredient in adhesives, cutting oils, and aerosol formulations pesticide. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

The relationship between particle size and foliage injury was shown in work with liquefied gas aerosol formulations of hexaethyl tetraphosphate for greenhouse applications (I). Particles larger than 20 microns diameter injured some varieties of foliage. Increasing pressure and using smaller nozzles lowered the mass median diameter but did not eliminate the maximum sized particles. The problem was finally solved with a low-concentration formulation, in which the particles larger than 20 microns in diameter could be eliminated. 

Retention of viscous purulent secretions, which contain high concentrations of extracellular DNA—released by degenerating leukocytes that accumulate in response to infection [24]—in the airways contributes both to reduced pulmonary function and to exacerbations of infection [24,25], Digestion of DNA polymers in purulent secretion with DNAse (dornase-a or Pulmozyme) has been shown to reduce sputum viscosity in cystic fibrosis patients. The availability of recombinant DNAse has allowed its use in an aerosol formulation to deliver the enzyme into the deep lung alveoli of CF patients. The purihed glycoprotein contains 260 amino acids with an approximate molecular weight of 37,000 daltons [26], The primary amino-acid sequence is identical to that of the... 

One of the most important direct uses for nitromethane is in the stabilization of halo-genated hydrocarbons. For example, small amounts of nitromethane are widely used in industry to form stable non-corrosive mixtures with 1,1,1-trichloroethane for vapour degreasing, dry cleaning and for cleaning semiconductors and lenses. It is also used to stabilize the halogenated propellants for aerosols and to inhibit corrosion on the interiors of tin-plated steel cans containing water-based aerosol formulations (Markofsky, 1991 Angus Chemical Co., 1998). 

Even when the appropriate inhaler is chosen, the influence of the disease state cannot be ignored. Disease states can influence the dimension and properties of the airways and hence the disposition of any inhaled drug. Thus, great care must be taken when extrapolating the findings based on intratracheal administration to different animal species in order to predict deposition profiles after inhalation of aerosol formulations by patients suffering from airway disease. DPIs are not appropriate in many diseases when the ability to have sufficient airflow is hindered. Since many diseases that we would like to treat via pulmonary administration of biomolecules cause a decrease in airflow, we must be careful in the decision of which type of inhalation mechanism to choose. 

Dalby RN, Byron PR. Comparison of output particle size distributions from pressurized aerosols formulated as solutions or suspensions. Phann Res 1988 5(1) 36—39. 

Lucas P, Anderson K, Potter UJ, Staniforth JN. Enhancement of small particle size dry powder aerosol formulations using an ultra low-density additive. Pharma Res 1999 16(10) 1643-1647. 

The active substance is mechanically ejected from a blister through laser-drilled nozzles with a diameter of a few pm and integrated into the blisters by means of punch, to produce a mist consisting of drops measuring 1-6 pm. The blister is inserted into an electronically controlled dosing unit that measures the airstream and induces aerosolization in synchrony with inspiration. The bioavailability of morphine sulphate (total dose 8.8 mg) blistered in portions of 1.2 mg was 75% of that on intravenous administration (dose 4 mg), which is much higher than conventional aerosol formulations (Gonda et al., 1999 Otulana etal., 1999). 

This product may be applied with a trigger pump or by aerosol. Formulation Properties ... 

Evans, R. M., and S. J. Farr. 1992. The development of novel, pressurized aerosols formulated as solutions J. Biopharm. Sci3 33-40. 

Clarke, M. J., Layzell, G., Tobyn, M. J., and Staniforth, J. N. The role of fine particle lactose in agglomerated dry powder aerosol formulations. J. Pharm. Pharmacol. 50(suppl) 186, 1998. 

V. Windisch, C. Karpenko, and A. Daruwala, LC assay for salmon calcitonin in aerosol formulations using fluorescence deri-vatization and size exclusion chromatography, J. Pharm. Biomed. Ana ., 70 71 (1992). 

Lipid aerosol formulations of nitroglycerin are also available, which are far more stable than the tablets, with a prolonged (3-year) shelf life. Sprayed directly onto the tongue, they produce relief of anginal pain within 2 min with a duration of effect of up to 30 min. However, it has been shown that the use of different aerosol vehicles markedly influences the bioavailability of the dmg, which obviously has important therapeutic implications. 

Drags to be administered to the nasal cavity are generally formulated as nasal drops, which deposit a film of drag solution, or nasal sprays which deposit an aerosol of particles, droplets or particles suspended in droplets. For absorption of aerosol formulations, deposition of the aerosol must occur followed by dissolution of solid particles if applicable. 

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