Aerosols are solid or liquid particles suspended in the air ranging in size from 10 -7 to 10 -3 cm. Solid particles larger than 10 -3 cm are classified as dust (see). Aerosols from solid particles are also called smokes, and aerosols from liquid particles are also called mists. Aerosols are classified depending on their nature (organic, inorganic), toxicity and nature of the particles (bacterial) and other features. Many erosions (toxic, radioactive, bacterial, etc.) can have bad influence on a person as directly (causing various diseases), and indirectly (reducing transparency, causing the death of green spaces).

For personal protection against harmful aerosols, special dressings are used, (see), (see) and suits. To clean the air from aerosols, various methods and technical devices (filters, cyclones, etc.) are used. Due to the fact that harmful aerosols enter the body mainly through the respiratory system and can cause mass diseases, measures to (see) from industrial and other pollution by harmful substances are essential.

Aerosols are widely used in various areas medicine - aerosol therapy (see), inhalation, etc. Aerosols are obtained using special dispensers, generators, aerosol bombs and checkers.

Aerosols (Greek aer - air and German Sole, from Latin solutio - dissolution, solution) - dispersed systems consisting of small (10 -3 -10 -7 cm) solid or liquid particles suspended in air or other gaseous environment. They are divided into smoke (suspension of solid particles) and fogs (suspension of liquid particles). Aerosols are formed in natural conditions(dust, fog), during explosions, grinding, grinding, chemical reactions, sublimation, are created specially with the help of special generators. Radioactive aerosols are conditionally divided into "low active" (particle activity less than 10 -13 curies), "semi-hot" (10 -13 -10 -10 curies) and "hot" (more than 10 -10 curies). According to the method of formation, they are divided into natural (formed during the decay of natural radioactive substances), bomb (during nuclear explosions) and industrial (as a result of the activities of institutions and enterprises that use radioactive substances and sources ionizing radiation). About 90% of aerosols in the atmosphere have a particle size of less than 0.5 microns (usually 0.005-0.035 microns).

The air of working premises is usually dominated by particles up to 10 microns in size (40-90% - less than 2 microns).

Other equal conditions(degree of toxicity, etc.) hygienic value aerosols is determined primarily by the degree of dispersion (particle size) and weight concentration (number of particles per unit volume of air). The nature and rate of sedimentation of aerosols are determined meteorological conditions, size and shape of particles, density, etc. The settling rate of particles larger than 5 microns under the influence of gravity (without taking into account air turbulence and the influence of precipitation) is approximately determined by the Stokes law. Particles smaller than 5 microns move in accordance with the laws brownian motion and can be in the air long time in a balanced state. 1 cm 3 of dust particles, the diameter of which is 1 micron, has a total particle surface of the order of 6 m 2 . This huge specific surface area of ​​highly dispersed aerosols largely explains their high biological activity. One of important properties aerosols - the presence of electric charges (positive or negative) on their particles.

Aerosols find wide application in medicine (inhalation immunization, aerosol therapy, disinfection, disinsection and deratization, hygienic and toxicological studies etc.), agriculture(aerosols of insectifungicides, etc.) and other fields of science and technology.

To obtain aerosols, special sprayers, generators, aerosol bombs and aerosol bombs are used.

The most important is the effect of toxic aerosols on the respiratory system. As a rule, aerosols with particles of significant size (5-10 microns) are retained in the bronchi, only smaller particles penetrate into the alveoli. Particles smaller than 0.2 µm retain little in the alveoli and are almost completely eliminated during exhalation. Despite this, they can pose a significant health hazard. Aerosols in the form of plates (mica, feldspar) or fibers (glass or mineral fiber, textile fibers) can penetrate into the alveoli, having big sizes. The number of aerosol particles remaining in the lungs depends on their characteristics and can reach significant magnitude (see Pneumoconiosis). Entry into the lungs of "hot" radioactive particles can lead to focal necrosis of cells. Apparently, subsequent malignant degeneration of adjacent tissues is possible.

Special respirators are applied to protection against harmful aerosols (see), gas masks (see) and suits (see. Protective clothes). To clean the air from aerosols, a number of special methods(see Sanitary protection atmospheric air). See also Dust, Radioactive waste.

Liquid) particles suspended in air or any other gaseous medium. The totality of these particles - the dispersed phase - moves along with the gas dispersion medium. Aerosol particles can also be displaced relative to the medium itself as a result of Brownian motion, directed motion under the action of inertial forces, gravity, electric field, light pressure, under the influence of temperature difference or particle concentration in different places of the system.

When aerosol particles collide, they coagulate with the formation of flocculent accumulations (aggregates) that settle on the surface solid body or liquids. However, aerosol particles carrying electric charges of the same name (mainly due to the adsorption of ions present in the gas phase on aerosol particles) repel each other and are not prone to coagulation; such a system is able to maintain aggregative stability for a long time. The properties of aerosols depend on the size and shape of the particles, their chemical nature and structure, magnitude and sign of the electric charge, temperature, pressure, speed and nature of movement gas environment. Aerosol particle sizes are approximately in the range from 1 to 10 5 nm.

Aerosols are formed by dispersion (fine grinding of relatively large pieces of a solid body, liquid atomization) or by condensation of vapors of a substance in an initially homogeneous (homogeneous) gaseous medium.

AT last case as a result of spontaneous accumulation of molecules (density fluctuations) in the volume of supersaturated vapors, nuclei of a new dispersed phase are formed, which then turn into stable liquid or solid microparticles. Dispersion leads to education atmospheric dust in the process of weathering rocks, soil erosion, volcanic eruptions; similarly, aerosol pollution is formed during mechanical processing building materials, mining of solid minerals, production and processing of powdered products. dispersion using various means spraying, receive aerosols with a liquid dispersed phase for various industrial and domestic purposes. By condensation in natural conditions, when atmospheric air is supersaturated with moisture, clouds and fogs arise. With incomplete combustion of fuel and in some chemical processes smoke is formed - aerosols with solid microparticles, in the atmosphere of environmentally unfavorable industrial areas - smog with heterogeneous aerosol particles that are both in liquid and solid state of aggregation.

Aerosols are widely distributed in nature (see, for example, Atmospheric aerosol), play big role in various technological processes, affect the health and everyday life of a person. In the form of aerosols, paints and varnishes are used to create decorative and protective coatings in mechanical engineering and construction. By spraying with the help of nozzles, liquid and solid fuels are converted into an aerosol when burned in thermal power plants, jet engines. Aerosol cans with various household chemicals are widely used in Everyday life person. In aerosol form, household insect and agricultural pest control products, some perfumery and hygiene products, medicines (aerosol therapy), disinfectants, etc. are used. The ability of aerosols to scatter and absorb light is used in military affairs (masking smokes) and pyrotechnics (colored smokes).

Harmful to health aerosols that occur in underground workings during mining hard coal and ore raw materials, in the factory shops of metallurgical and chemical enterprises, during blasting, burning fuel or organic waste from production and consumption. They pollute the air and, acting on the respiratory and skin human, can cause acute and chronic diseases (including various pneumoconiosis). Particularly harmful to health are radioactive aerosols (see the article Hot particles), as well as aerosols containing pathogens, toxic chemicals. A great danger is flammable and explosive dust (for example, coal, flour, wood, cotton, aluminum), which can be formed in coal mines, as well as in flour-grinding, woodworking, textile and other enterprises processing bulk and dusty materials.

There are many effective means protection against harmful aerosols: from industrial air filters and various types of absorbers (see Dust removal, Mist removal) to individual funds protection (gas mask, dust respirator, etc.). In the fight against highly dispersed aerosols, the Petryanov filter is very effective - a layer of non-woven material made of thin polymer filaments that traps aerosol particles different origin. However major problem modern production, in many cases successfully solved, remains the creation and development of such technological processes, at which the formation of aerosol pollution would be completely excluded.

The processes of formation and destruction of aerosols in the surrounding space, including outer space, never stop. In one year, about 20 tons of various solid and liquid substances per 1 km 2 earth's surface. Aerosol particles enter the atmosphere from the surface of the land, open water bodies, from space. Aerosol destruction various origins and the composition occurs naturally or it is caused artificially. The main processes leading to the decay of aerosols are the sedimentation of enlarged aerosol particles under the action of gravitational or centrifugal forces and the deposition of particles on the surface of a solid or liquid under the action of attractive forces of a molecular or electrostatic nature, as well as the evaporation of particles if they are formed from volatile substances.

Aerosols of one type can be used to destroy other types of aerosols. For example, in coal mines, areas of harmful and explosive coal dust are sprayed with an aqueous spray (usually with surfactant additives) that is obtained using special sprayers. Water droplets capture coal particles and, together with them, are deposited on broken coal, mine walls and other surfaces, cleaning the environment. air space. Another example: the artificial induction of rain by spraying chemical reagents into atmospheric clouds, initiating the process of enlargement of water microdroplets.

Lit .: Green H., Lane V. Aerosols - dusts, fumes, fogs. L., 1969; Rudenko KG, Kaminkov AV Dedusting and dust collection in the processing of minerals. 3rd ed. M., 1987; Petryanov Sokolov I. V., Sutugin A. G. Aerosols. M., 1989; Shchukin E.D., Pertsov A.V., Amelina E.A. colloid chemistry. M., 1992. S. 328-335; Zimon A.D. Aerosols, or Genie, escaped from the bottle. M., 1993.

Condensation aerosols also include aerosols formed during chemical and photochemical reactions in the gas phase, for example, in the production of Si and Ti by their thermal hydrolysis in a flame. The most important of these aerosols is smog, which occurs in the atmosphere as a result of photochemical reactions between gaseous impurities under intense sunlight. A feature of the products of chemical reactions is the possibility of a catalytic effect of condensed particles on the transformation starting materials. Condensation aerosols can also be formed due to the evaporation of bodies, including as a result of exposure to laser radiation, followed by vapor condensation.

Dispersion aerosols with solid particles (dust) are formed in the atmosphere under natural conditions, as well as in mines, pouring powders (flour, chalk), etc. Aerosols with a liquid dispersed phase (sometimes called sprays) arise from the disintegration of jets or films of liquid, for example, when liquid is sprayed in engines internal combustion. Important practical cases the formation of liquid aerosols - spraying under the influence of a source of acoustic vibrations located in it, the destruction of jets when exposed to an electric potential field.

Often there are mixed aerosols, consisting of particles of different origin. Thus, during explosive destruction, as a rule, the substance is dispersed and evaporated, followed by vapor condensation and the formation of aerosols.

Main characteristics. The dispersion medium is characterized chemical composition, temperature, pressure, degree of ionization, parameters of external physical fields, flow velocity field, the presence of turbulence and its parameters, the presence and magnitude of temperature gradients and components. The most important parameters dispersed phase of aerosols - volume fraction particles and their mass fraction, the number of particles per unit volume (counting concentration) n p, the average size particles dp and her electric charge. The parameters of the dispersed phase of atmospheric aerosols at normal temperature and pressure are: d p 5*10 8 -10 -2 cm, p p 1-10 8 cm -3 , 10 -18 -10 -1 , 10 -19 In the upper atmosphere etc\u003d 10 5 -10 14 cm -3, 10 -19 -10 -33, Along with the average values, the dispersed phase is characterized by the distribution of particles by size and by the magnitude of the electric charge (the latter even for monodisperse aerosols). If the substance of the dispersed phase is radioactive, it is also necessary to know the specific activity of the particles.

The interaction between the dispersed phase and the dispersion medium is determined by the processes of transfer of mass, energy, momentum, electric charge, etc., as well as phenomena at the phase boundary. Transfer processes are described by equations, end view which depends on the Knudsen number Kp = , where is the mean free path of gas molecules, dp- aerosol particle diameter At Kp 1 and, therefore, dp the dispersion medium can be considered as continuous; in this case, one speaks of a continual regime of transfer processes. If Kp 1, aerosols can be considered as a mixture of two gases, the molecules of one of which - aerosol particles - are much heavier than the dispersion medium. In such a system, the transfer processes are described using the equations of the gas-kinetic theory (the so-called free molecular regime). Finally, at Kp 1 (particle diameter at atmospheric pressure 0.01-1.0 µm) transfer processes are calculated by approximate methods of rarefied dynamics (transient mode). The accuracy of the equations describing the transport processes in the free molecular and continuum regimes at the boundaries of the indicated particle size range, which determines the Kp values, is about 10%. The processes of transfer in aerosols are affected by the movement of particles relative to the medium under the influence of external. forces or by inertia; it is characterized by the Mach number Ma= , where and p-speed of particles relative to the medium, -velocity thermal motion environment. When analyzing the nature of momentum transfer, the Reynolds number Re = 4Ma/Kn is often used instead of the Mach number.

Properties The most important properties of aerosols are the ability of particles to remain in suspension, to move predominately. as a whole and stick to each other or to any surface with a probability equal to one when colliding. In a medium at rest, aerosol particles are maintained in suspension in the gravitational field due to their own. thermal motion, the energy of which for particles of any mass is equal to 3 / 2 kT, where k- Boltzmann's constant, T - absolute temperature, and due to the exchange of energy with the molecules of the medium. The particle height distribution is usually characterized by the parameter (Perren height), where

The acceleration due to gravity, is the mass of the particle. For sufficiently small particles, when H p far exceeds their linear size, the energy of thermal motion is sufficient to maintain the particles in suspension even in the absence of a dispersion medium. If the particle size is comparable to HP or more than it, then to keep the particles in suspension, it is necessary additional energy obtained by collisions with the molecules of the medium. The ratio between these two types of energy is characterized by the Schmidt number, where is the concentration of gas molecules, is the length of their free path. For Sc 10 5, only the exchange of energy between the particles and the medium matters. At 10 7 D pT and medium D T . The value is called the degree of flow, - degree of entrainment of particles. The ability of aerosol particles to remain in suspension without the application of a disturbing effect to dispersion medium distinguishes aerosols from a fluidized (boiling) bed, which is also a two-phase system with a gaseous dispersion medium.

Aerosol particles can move relative to the medium, mainly under the influence of external fields, such as the gravity field in which the particles settle, as well as inertial forces (if the medium moves at an accelerated rate), temperature and concentration gradients. The particle speed is determined by ext. the force and force of resistance of the medium to the movement of particles. In most cases, these forces balance each other, and the particles move with constant speed; only in environments with strong turbulence and in acoustic fields movement is accelerated. Speed ​​ratio v of the stationary motion of a particle to the force acting on it is called the mobility of the particle AT. In continuous mode , where is the viscosity of the medium (Stokes formula). This formula allows you to calculate In with with an accuracy of up to 10% for Kp\u003e 0.1 and Re A 1 Kp), where A 1 is an empirical constant. In the free molecular mode at Kp > 10 B = (Ai + Q/3) (Epstein's formula), where Q is another empirical constant. Transient to calculate AT a number of empirical formulas have been proposed, of which the Millikan formula is the most common: , where b - empirical constant. For oil mist drops, for example, in the Epstein formula ( A 1 + Q) = 1.154, in the Millikan formula A 1 = 1.246, Q = 0.42, b = 0.87. Meaning AT determines the coefficient of thermal diffusion of particles D=kTB, called sometimes by the Brownian diffusion coefficient.

If there are temperature gradients in the dispersion medium or aerosol particles move even in the absence of external. forces; the corresponding phenomena are called thermo- and diffusiophoresis. In the free molecular mode, thermophoresis is similar to thermal diffusion; in the continuum mode, it is due to the tangential force acting on the particle due to the occurrence of a gas flow (thermal slip) near the inhomogeneously heated surface of the particle. special case thermophoresis - photophoresis: the movement of particles under the action of light irradiation. This effect is due to uneven heating of the particles and the medium, mainly due to their different ability to reflect and absorb light. Diffusion phoresis due to a gradient at a constant total pressure occurs, for example, near surfaces or condensation.

Aerosol particles smaller than 1 µm always adhere to solid surfaces when they collide with them. The collision of particles with each other during Brownian motion leads to coagulation of the aerosol. For monodisperse aerosols with spherical particles, the coagulation rate dn / dt \u003d - Kp 2, where n is the number of particles per unit volume, To-t. called coefficient Brownian coagulation. In continuous mode To calculated according to the Smoluchovsky formula, in free molecular weight - according to the formula , where and R - average speed thermal motion of aerosol particles, is a coefficient that takes into account the influence of intermolecular forces and for various substances having a value from 1.5 to 4. For the transition mode, the exact formulas for calculating To does not exist. In addition to Brownian motion, aerosol coagulation may have other causes. The so-called gradient coagulation is due to the difference in particle velocities in the shear flow; kinematic - different speed motion of particles relative to the medium (eg, in a gravitational field); turbulent and acoustic - by the fact that the particles different sizes come together and collide, being in varying degrees carried away by pulsations or sound vibrations environment (the last two reasons are significant for inertial particles with a size of at least 10 -6 m). The coagulation rate is affected by the presence of an electric charge on the particles and external electric fields.

Aerosol particles are capable of acquiring an electrical charge if they are formed by condensation on ions. Uncharged particles can capture gas ions moving in a direction towards particles in an external field or diffusing in a medium. Dispersed particles can also acquire a charge in the process of formation - when liquids are sprayed (balloelectric effect) or powders are sprayed (triboelectric effect), when illuminated (photoelectric effect), radioactive decay etc. In aerosols generated by high temperature, for example, during evaporation and subsequent condensation of vapors, charges on particles also arise as a result of thermionic or thermionic emission.

Aerosols have pronounced light scattering, the regularity of which is determined by the range of values ​​of the parameter , where is the radiation wavelength. At > 1, the light scattering cross section increases with decreasing particle size. With a decrease, the cross section becomes proportional. Therefore, highly dispersed particles scatter visible, and even more so, IR radiation weakly. For a fixed particle size, the light scattering cross section decreases proportionally to . When light is scattered by aerosol particles, the state of radiation polarization changes. Measurements of light scattering and the polarization state of the scattered light are used to determine particle sizes and size distributions. See also

At the word "aerosol" we usually imagine a spray can from which something useful is sprayed - either a remedy for cockroaches and flies, or a medicine for the throat. This idea is, in principle, true, but only partly.

To begin with, let's figure out what meaning is put into the word "aerosol" in general. From the point of view of physics, an aerosol is a kind of disperse system. What is a dispersed system? This combination physical bodies(in this case they are called phases), which are in different states of aggregation (solid, liquid or gaseous) or even in one (except for those cases when both bodies are gaseous - in this case, a dispersed system will not work), but they do not mix with each other and do not enter into chemical reaction, and one of them (it is called the dispersive phase) is evenly distributed in the second (dispersion medium). state of aggregation each of these two components just determines the type of aerosols.

So, if the dispersed medium is gaseous, and the dispersed phase is liquid or solid distributed in it, this is an aerosol. To be precise, it will be one of two types of aerosols, and we encounter both types almost every day. So, clouds floating above the earth, or fog covering the valleys in the predawn hour, are also aerosols. In this case, the smallest droplets of liquid are suspended in a gaseous dispersion medium. Something similar can be observed near fountains or waterfalls.

Smoke is also an aerosol, in this case, the dispersed phase suspended in the air is represented by the smallest solid particles of unburned fuel. And even the dust in the air is also an aerosol! Such an aerosol is called coarse dispersion. Pollen suspended in the air during flowering, haunting those who suffer from allergies, is also an aerosol.

But this is not the most surprising. Aerosols are ... alive! This can be said if the scattered in the air solid particles are micro-organisms such as bacteria. For the first time, a similar phenomenon was discovered by the French scientist Louis Pasteur - explaining in this way how infectious disease can be transmitted by airborne droplets. Such a "living aerosol" is otherwise called aeroplankton, and these bacteria were found not only near the earth's surface, but also at a fair height - 70 km above the Earth's surface! So, we have more or less figured out aerosols in nature, but what kind of aerosols does a person create for his own benefit?

First of all, aerosols are used in medicine. Even in ancient times, the rooms where the sick were kept were fumigated with smoke generated during the burning of medicinal plants. It brought a certain benefit, but in our time there are more effective ways such as inhalation. The drug solution is either heated or subjected to some other effect (for example, ultrasound), as a result of which it turns into an aerosol, which the patient inhales. The medicine thus penetrates deeply into Airways- this is indispensable, for example, in the treatment of bronchitis. Another way to turn a drug into an aerosol is to atomize the liquid with an atomizer, a device that operates due to a difference in pressure. An aerosol can be used to treat a sore spot “targeted” - for example, an antibiotic in the form of an aerosol that is sprayed on the throat, even for pregnant women. At the same time, it is not as painful as lubricating the throat with medicine.

In the form of aerosols, not only medicines are used, but also deodorants, already mentioned insect poisons, paint, and even weapons (gas cartridges). And another type of aerosol, unfortunately, created by man, is smog.

MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION

GENERAL PHARMACOPEIAN AUTHORIZATION

Aerosols and sprays OFS.1.4.1.0002.15

Instead of Art. GF XI "Aerosols"

Aerosols - dosage form, which is a solution, emulsion or suspension active ingredients pressurized propellant in a sealed package (aerosol can) equipped with a valve-spray system that releases medicinal product in the form of a dispersion of solid or liquid particles in a gas, the size of which corresponds to the route of administration.

Sprays are propellant-free aerosols whose contents are released by air pressure generated by a mechanical pump-type atomizer or by compressing a polymer package. Compared to aerosols, sprays are a more coarse system.

Aerosols are two-phase (gas and liquid) or three-phase (gas, liquid and solid or liquid) systems. Two-phase aerosols consist of a solution of the active substance in a liquefied propellant with the addition of solvents to ensure the solubility of the active substances. Three-phase aerosols consist of a suspension or emulsion of active ingredients and a propellant.

Three-phase aerosols include foam aerosols, which are emulsions containing active ingredients, surfactants, aqueous or non-aqueous solvents and propellants. If the propellant is part of the dispersed phase (oil-in-water emulsion), a stable foam is formed when the contents are released.

Sprays are single-phase (liquid) or two-phase (liquid and solid or liquid) systems.

TECHNOLOGY FEATURES

Excipients as part of aerosols and sprays (solvents, propellants, surfactants, film formers, flavoring agents, antimicrobial preservatives, antioxidants, etc.) must be approved for medical use, provide optimal technological characteristics of the dosage form, be compatible with other components of the dosage form and material packaging. Excipients in the composition of aerosols for inhalation should not adversely affect the function of the mucous membrane of the respiratory tract.

Solvents: water, ethyl alcohol, fatty oils of vegetable and animal origin, mineral oils, glycerin, ethyl acetate, ethyl chloride, propylene glycol, dimexide (dimethyl sulfoxide), polyethylene oxides with various molecular weights, polysiloxane compounds, ethyl cellulose, etc.

Surfactants: polysorbates (tweens), foams, pentol, preparation OS-20, emulsion waxes, emulsifier No. 1, emulsifier T-2, synthetic fatty primary alcohols, triethanolamine salts of higher fatty acids, oleic acid, etc.

Film formers: derivatives of cellulose, acrylic acid, etc.

Corrigents: sugar, lemon acid, sorbitol, essential oils, thymol, menthol, etc.

Antimicrobial preservatives: methyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, ethyl parahydroxybenzoate, sorbic and benzoic acids, sodium benzoate, ethonium, catamine AB, etc.

Antioxidants: butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, ascorbic acid, etc.

Propellants (used in aerosols): liquefied gases, such as low molecular weight paraffinic hydrocarbons such as propane and butane, compressed gases such as nitrogen, nitrous oxide, carbon dioxide, and halogenated hydrocarbons (freons or freons). Mixtures of propellants can be used to create optimal physico-chemical characteristics of the aerosol.

Aerosols and sprays are placed in a package, which must be made of a material that is inert with respect to the contents of the package: metal, glass, plastic, or combinations thereof. Aerosol glass containers must be protected with a plastic coating. Aerosol cans must withstand an internal pressure of at least 1 MPa at 20 ºС.

Depending on the type and purpose of the package, it must be equipped with a spray device. continuous action(non-metered aerosols and sprays) or dosing spray device (metered aerosols and sprays). The materials used in the manufacture of spray devices (plastic, rubber, metal) must be inert with respect to the contents of the package.

The spray device must regulate the release of the contents of the package during use: the speed and completeness of the release, the particle size of the dispersion, the uniformity of dosing. The valve-dispensing device for aerosols must ensure the tightness of the package when not in use.

TESTS

Depending on the dosage form, quality control of aerosols and sprays includes an assessment of the pressure in the package, the tightness of the package, checking the valve, determining the percentage of output of the package contents, medium weight dose, number of doses per package, dosing uniformity, mass uniformity. For non-inhalation aerosols and sprays containing a suspension of active substances, the particle size is determined, for inhalation aerosols - the respirable fraction.

For aerosols and sprays, which are emulsions and suspensions, separation during storage is allowed, but they must be easily re-emulsified and resuspended with shaking to ensure uniform distribution active ingredient in a medicinal product.

Aerosols intended for inhalation must comply.

Packing pressure

Pressure measurement is carried out only for aerosols in which compressed gases are propellants.

The packages are kept at room temperature for 1 hour and a manometer (accuracy class 2.5) measure the pressure inside the package, which must meet the requirements of the pharmacopoeia article or regulatory documentation, but should not exceed 0.8 MPa (8 kgf / cm 2).

Packing tightness(for aerosols)

Method 1. The aerosol can without a cap and atomizer or nozzle is completely immersed in a water bath at a temperature of (45 ± 5) ° C for not less than 15 min and not more than 30 min for a glass container and not less than 10 min and not more than 20 min for metal. The water layer above the valve stem must be at least 1 cm thick. No gas bubbles should be observed.

Method 2. Select 12 previously unused aerosol packages. Each package without a cap and atomizer or nozzle is weighed to the nearest 0.001 g ( m 0) and left upright at room temperature for at least 3 days. The aerosol can is then weighed again to the nearest 0.001 g ( m 1).

Record the duration of the test in hours ( T).

The aerosol package is released from the contents in accordance with the method specified in the monograph or regulatory documentation. Weigh the empty package to the nearest 0.001 g ( m 2), calculate the average weight of the content to the nearest 0.001 g ( m 3) according to the formula:

n– number of aerosol cans tested.

Calculate the leakage rate of the contents of the package in grams per year ( Vm) according to the formula:

Calculate the rate of leakage of the contents of the package per year as a percentage of the average mass ( V%) according to the formula:

Unless otherwise stated in the monograph or normative documentation, the average annual leakage rate for 12 packages should not exceed 3.5% of the average weight of the contents of the package and for none of them should not exceed 5.0%. If for at least one package the leakage rate exceeds 5.0% per year, but for none of the packages it exceeds 7.0%, the leakage test is carried out on 24 additional packages. No more than 2 out of 36 packages may have a leakage rate greater than 5.0% and none of them shall have a leakage rate greater than 7.0% per year.

If the mass of the contents of a package is less than 15 g, the average leakage rate for 12 packages must not exceed 525 mg/year and none of them must exceed 750 mg/year. If for at least one package the leakage rate exceeds 750 mg/year (but not more than 1.1 g/year), then the leakage test is carried out on 24 additional packages. No more than 2 packages out of 36 may have a leakage rate greater than 750 mg/year and no leakage rate must exceed 1.1 g/year for any package out of 36.

Outlet of the contents of the package

The test is carried out for unmetered aerosols and sprays. The package is weighed together with a sprayer or nozzle with an accuracy of 0.01 g ( m 4). By pressing the sprayer or nozzle, remove all the contents from the package and weigh the package again together with the sprayer or nozzle with an accuracy of 0.01 g ( m 5).

Percentage content yield ( X) is calculated by the formula:

where m 6 - the mass of the contents indicated on the label, g (or obtained by multiplying the nominal volume by the density of the drug).

Unless otherwise specified in the monograph or normative documentation, the percentage of release of the contents of the package must be at least 90%, and the result is the arithmetic mean obtained when determining the percentage of release of the contents from 3 packages.

Dose Mass Uniformity

The test is carried out for metered-dose aerosols and sprays containing solutions. The test for inhalation aerosols is carried out in accordance with (Test "Uniformity of Delivered Dose").

One dose is released and discarded. After at least 5 seconds, shake the package for 5 seconds, release again and discard one dose. Repeat the indicated procedure 3 more times, unless otherwise indicated in the monograph or normative documentation. Weigh the package. Shake the pack for 5 s, release and discard one dose, reweigh the pack. The mass of the released dose is calculated from the difference.

The test is repeated for 9 more doses specified in the monograph or normative documentation. Calculate the average mass dose and deviation individual values from the average weight of the dose.

The medicinal product is considered to have passed the test if no more than 1 out of 10 individual masses deviates from the average mass by more than 25%, but not more than 35%. If 2 or 3 results fall outside the 75-125% range, the test is repeated with 20 other doses. No more than 3 out of 30 values ​​can be outside the range of 75 - 125%, and all values ​​must be between 65 and 135%.

Number of doses per pack

The test is carried out for metered-dose aerosols and sprays.

Method 1 Release the contents of one package, releasing doses at intervals of at least 5 s. The number of doses released is recorded.

It is allowed to carry out the test simultaneously with the determination of the uniformity of dosing.

Method 2 The package is weighed together with a sprayer or nozzle with an accuracy of 0.01 g ( m 2). By pressing on the sprayer or nozzle, all the contents are released from the package and the package is again weighed together with the sprayer or nozzle with an accuracy of 0.01 g ( m 5).

Average number of doses ( n cf) in one package is calculated by the formula:

where m cf is the average weight of one dose, g.

The number of doses obtained as a result of the test must not be less than that indicated on the label.

Particle size

The test is carried out for non-inhalation aerosols and sprays containing a suspension of the active substances. Methods of determination and requirements for particle size should be specified in the monograph or normative documentation.

Respirable fraction

The test is carried out for inhalation aerosols in accordance with .

Uniform dosing

The test is carried out for metered-dose aerosols and sprays containing emulsions or suspensions. The test for inhalation aerosols is carried out in accordance with.

Control of this indicator should be carried out not only for doses released from one package, but also for doses received from different packages. The dose selection procedure should include selection of doses at the beginning, in the middle and at the end of the use of the drug.

The test is carried out using an apparatus or apparatus capable of quantitatively retaining the dose released from the nebulization device. Shake the package for 5 seconds, release and discard one dose. After at least 5 seconds, shake the package again for 5 seconds, release and discard one dose. Repeat the indicated procedure 3 more times, unless otherwise indicated in the monograph or normative documentation. After 5 seconds, one dose is released into the receiver of the apparatus. The contents of the receiver are collected by successive washings and the content of the active substance in the combined washings is determined.

The test is repeated for 9 more doses specified in the monograph or normative documentation.

The drug passes the test if 9 out of 10 results are between 75% and 125% of the mean, and all results are between 65% and 135%. If 2 or 3 results fall outside the 75-125% range, the test is repeated with 20 other doses. No more than 3 out of 30 values ​​can be outside the range of 75 - 125%, and all values ​​must be between 65 and 135%.

For aerosols and sprays containing several active substances, a uniform dosing test must be carried out for each substance.

PACKAGE

In accordance with the requirements.

MARKING

In accordance with the requirements. The labeling of aerosols should include warning labels: “Keep away from the heating system and direct sun rays”, “Do not open”, “Protect from drops and bumps” and others if necessary.

STORAGE

In accordance with the requirements. Packed to ensure stability through the stated expiration date medicinal product, in a place protected from light at a temperature of 8 to 15 ° C, unless otherwise indicated in the monograph or regulatory documentation.