Quality Control of Aerosols: As pharmaceutical aerosols are “pressurized packages”, many tests are necessary to ensure proper performance of the package and safety during use and storage. Pharmaceutical aerosols can be evaluated by a series of physical, chemical, and biological tests.
(A) Flammability and Combustibility Tests:
- Flame extension
(B) Physico-chemical Characteristics:
- Vapour pressure
- Moisture content
- Identification of propellant (s)
- Aerosol valve discharge rate
- Spray pattern
- Dosage with metered valves
- Net contents
- Foam stability
- Particle size determination
(D) Biologic characteristics:
Flammability and Combustibility Tests
Table of Contents
1. Flash Point: Standard tag open cup apparatus is used to determine the flashpoint of aerosol product. The product is chilled to a temperature of 25oF. This liquid is placed in the tag open cup apparatus. The temperature of the liquid is increased slowly. The temperature at which the vapors ignite is taken as the flashpoint.
2. Flame Projection: The product is sprayed for about 4 seconds in a flame. Depending on the nature of the formulation, the flame is extended. The length of the extended flame is measured.
1. Vapour Pressure: The vapor pressure is determined by a pressure gauge. Excess variation of vapor pressure in the containers indicates the presence of air in the headspace.
2. Density: The density of an aerosol system may be accurately determined using a hydrometer or pycnometer. The hydrometer is placed into a glass pressure tube. A sufficient sample is introduced through the valve to cause the hydrometer to rise halfway up the length of the tube. The density can be read directly.
3. Moisture content: Karl Fischer apparatus is used to determine moisture content.
4. Identification of propellants: Gas chromatography and infrared spectrophotometry have been used to identify the propellants. The same techniques can also be used to determine the proportion of each component in a blend.
1. Aerosol valve Discharge Rate: The aerosol is weighed (w1 g) and discharged for a known period (t). The weight of aerosol (w2 g) after discharge is noted. Then rate is expressed as below;
2. Spray pattern: The spray pattern of aerosol valve discharge is determined as follows. An apparatus consists of a motor-driven rotating disc with an adjustable slit. The filter paper coated with dye talc mixture is attached to a rotating disc on one side (depending on the nature of the aerosol, an oil-soluble or water-soluble dye is used). The aerosol is sprayed onto fitter paper from the other side. The particles that strike the paper cause the dye to go into solution and to be absorbed into the paper.
3. Dosage with metered valves: When one attempts to test this, then either of the following must be observed.
(i) Reproducibility of dosage each time the valve is depressed.
(ii) Amount of medication received by the patient.
(i) Aerosol is actuated one or two times so that product is dispensed into the solvent. The amount of drug present in the solvent is determined by the assay technique.
(ii) Aerosol is actuated one or two times onto a material that absorbs the active ingredients. The amount of the drug that is absorbed is then determined by assay technique.
(iii) The accurate weight of the container (WI g) is noted. Aerosol is actuated for several doses (n times). Again the weight after dispensing is noted (WF g).
(iv) Aerosol is actuated to dispense the drug into an artificial respiratory system. The drug entered into the system is then determined.
4. Net Contents: To determine the net contents either of the following methods is used.
(i) Initial weight of the empty aerosol container is noted. After filling the weight is noted. The difference in the weights is net contents.
(ii) Weight of the filled container is noted. Aerosol is actuated to dispense the contents completely. Again the weight is noted. The difference in the weight is net contents. (However, provision must be made for the amount that is retained in the container).
(iii) Initial weight of the filled container is noted. By opening the valve, the total contents are removed. Again the weight of the container is noted. The difference in the weight is net contents.
5. Foam Stability: The life of foam can range from a few seconds to one hour or more. To determine the foam stability any one of the following methods is used.
(i) Actuate an aerosol to form the foam. Note down the time required for a complete collapse of foam by visual observation.
(ii) Actuate an aerosol to form the foam. Note down the time required for a given mass to penetrate the foam.
(iii) Actuate an aerosol to form the foam. Note down the time required for a rod that is inserted into the foam to fall.
(iv) Using rotational viscometer.
6. Particle size determination: To determine particle size cascade impactor is used. The principle behind the working of the cascade impactor is shown in Fig.1. Cascade impactor consists of series of nozzles and glass slides. When aerosol is actuated, larger particles impact first on the lower velocity stage. Then the smaller particles pass on and impact at the next stage i.e., the higher velocity stage. In such a way the particles ranging from 0.1 to 30 microns can be studied.
7. Leakage: Pass the crimped aerosol containers through the water bath. If any leaks are present, the evolution of air bubbles can be observed and the container is rejected.
1. Therapeutic Activity: Testing of aerosols for therapeutic activity is similar to testing of non-aerosol products. Apart from regular tests, the dosage is testing for inhalation aerosols. For topical preparations, adsorption of therapeutic ingredients is determined.
2. Toxicity: Toxicity testing includes the following;
(i) Irritation of affected area where the dose is administered.
(ii) Chilling of the skin due to evaporation of propellants.
(iii) Rise in temperature on the spraying of aerosol.
(iv) Inhalation toxicity studies though the preparation is for topical use. This can be done by exposing animals to vapors sprayed from an aerosol container.
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