Medicinal aerosol products

In the United States, use of CEC propeUants, designated as PropeUants 11, 12, and 114, is strictly limited to specialized medicinal aerosol products such as metered-dose inhalers. The physical properties and chemical names of these propeUents are given in Table 2. 

In the United States, use of CFC propellants, designated as Propellants 11, 12, and 114, is strictly limited to specialized medicinal aerosol products such as MDIs for asthma. Most of the countries of the world (except Third World countries) have also banned the use of CFC s for aU aerosols except pharmaceutical and medicinal use. The U.S. Food and Drug Administration (FDA) does not intend to prohibit the use of these CFCs in the exempted MDIs until such time as a sufficient number of alternative inhalers become available and their use has been accepted by both patient and physician. 

Blends of trichloromonofluoromethane and dichlorodifluoromethane (propellant 11/12) or propellant 11/114/12 produce vapor pressures of 103 84 kPa (15-70 psig) at 21°C, which adequately cover the range of pressures required to produce the proper particle-size distribution for satisfactory aerosol products. Trichloromonofluoromethane is unique among the chlorofluorocarbon propellants in that it is a liquid at room temperature and atmospheric pressure and can be used to prepare a slurry with insoluble medicinal agents. 

The aerosol container has enjoyed commercial success in a wide variety of product categories. Insecticide aerosols were introduced in the late 1940s. Additional commodities, including shave foams, hair sprays, antiperspirants, deodorants, paints, spray starch, colognes, perfumes, whipped cream, and automotive products, followed in the 1950s. Medicinal metered-dose aerosol products have also been developed for use in the treatment of asthma, migraine headaches, and angina. 

Manufacture of immunological veterinary medical products Manufacture of medicinal gases Manufacture of herbal medicinal products Sampling of starting and packaging materials Manufacture of liquids, creams, and ointments Manufacture of pressurized metered-dose aerosol preparations for inhalation... 

There are a large number of propellant-product combinations. Common propellants include halocarbons (although the use of CFCs is widely abandoned), compressed air, carbon dioxide, nitrous oxide, butane, and propane. Aerosols are used in industrial applications and consumer articles to dispense or apply cosmetics and perfumes, paints and coatings, medicines and drugs, starches, pesticides, disinfectants, deodorants, and many other materials. 

Most product information leaflets for nebulised medicine formulations discourage mixing of marketed formulations but in practice different formulations are frequently mixed to increase patient comfort. Particularly CF patients tend to combine medicines in order to save time as well as to overcome adverse effects (e.g. bronchoconstriction) of one active substance (antibiotic) by another (salbutamol). They also tend to refill their nebuliser with a new medicine without emptying and cleaning the nebuliser between the administrations. Relatively little has been reported in the literature about the compatibility of medicine mixtures, however, and interactions may be expected with respect to chemical and physical stability, droplet size distribution of the aerosol, nebuliser output rate and therapeutic effect. From a survey of studies on chemical stability, it is known that particularly domase alpha (Pulmozyme ) is incompatible with many other nebulised medicine formulations due to inactivation of the protein [63]. Additives, like stabilisers that work well in some medicine formulations, may be incompatible with other preparations and induce cloudiness... 

When specific administration devices (affecting parameters of relevance to the performance characteristics such as efficacy and safety of a medicinal product) are used substitution should not occur. Different dry powder inhalers, for example, generate aerosols of significantly different particle size. As a result, relevant variations may occur in lung deposition of the active substance. Therefore substitution of these t3q>es of products (e.g. dry powder inhalers) should not occur. 

During the preparation of medicines, steam, vapour, aerosols, dust and fumes can be released, which may pose a health risk for the operator. It is not always possible to change the process releasing these hazardous substances. As a consequence it can be necessary to protect operators in preparation or quality control areas from exposure to the product or the active substance. This can be done by active ventilation and exhaust and by filtration in order to protect the environment (see also Sect. 26.4.1). The appropriate equipment may be fume cupboards, moveable exhaust ducts, powder exhaust units, (bio)safety cabinets and isolators. Fumes, gas mixtures and volatiles might be absorbed by special filters, but in pharmacy practice only the technique of exhausting and screen filtration is usually used. 

Where heavy exposures occur, dichlorvos results in significant morbidity and mortality. These exposures normally involve accidents which arise during pesticide use rather than with the employment of small aerosols of veterinary medicinal product, or they may arise from suicide attempts. " Dichlorvos is also genotoxic... 

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