Courses:Pulmonary Drug Delivery/Quality control tests for aerosol
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7.Quality control tests for aerosol
What is the quality control tests conducted on aerosol products? Explain in detail.
There are quality control tests carried out on the raw materials, during production and on the finished products.
Let us look into the details of tests carried out on raw materials. These tests are conducted to determine the quality, safety and performance of each of the raw material which is determined by a specification value.
Specifications for raw materials
PropellantsA
All propellants are shipped to the user with an accompanying specification sheet. A sample of raw material is removed and tested: 1.Determining its vapor pressure and compared to specifications 2.Determining its density and compared to specifications 3.Identity is determined by gas chromatography as well as to determine the composition of the blend of propellants. 4.Purity and acceptability of propellants is tested by moisture, halogen and non volatile residue determinations.
Valves, Actuators and Dip tubes: These parts are subjected to both physical and chemical inspection. Additional tests on the valve to ensure that the valves are fit to be used. These tests include using specific test solution and procedure for acceptance of the valve.
Containers Containers are sampled according to standard sampling procedure. Both uncoated and coated metal contains are examined for defects in the lining. Glass containers are examined for flaws. The dimensions of the neck and other parts are checked to determine conformity to specifications. The weight of the container is also checked.
Testing during manufacture
Weight checking Carried out periodically, by adding to the filling line, tared empty aerosol container. After it is filled with concentrate remove and accurately weighed. The same procedure is adopted to check the weight of the propellant that is being added. As a further check, the finished container is weighed to check the accuracy of the filling operation.
Leak Testing Is done by checking the crimping of the valve to ensure that there are no defective containers. This is usually done by measuring the ‘crimp’ dimensions of metal container and ensuring that they meet specifications. Final testing of the efficiency of the valve closure ids made by passing the filled containers through a heated water bath kept at 130 °F.
Spray Testing All aerosols are 100% spray tested. This clears the dip-tube of pure propellant (for products filled by pressure through stem, body and dip-tube_, to clean the dip-tube of pure concentrate (for products filled by pressure under the cap), and to check for defects in the valve and the spray pattern.
Testing of finished Product
Tests have been designed to ensure proper performance of the package and safety during use and storage. Thus pharmaceutical aerosols can be evaluated by a series of physical, chemical and biological tests including:
A.Flammability and Combustibility a.Flash point b.Flame extension B.Physicochemical characteristics 1.Vapor pressure 2.Density 3.Moisture content 4.Identification of propellant(s) 5.Concentrate – propellant ratio
C. Performance
1. Aerosol valve discharge rate
2. Spray pattern
3. Dosage with metered valve 4. Net contents 5. Foam stability 6. Particle size determination 7. Leakage
D. Biological characteristics
The flammability and combustibility of aerosol pharmaceuticals are determined by the following test procedures
Flame Projection: This test indicated the effect of an aerosol formulation on the extension of an open flame. The product is sprayed for about 4 seconds into a flame. Depending on the nature of formulations, the flame is extended, the exact length being measured with a ruler.
Flash Point: This is determined by use of a standard ‘Tag Open Cup Apparatus’. The aerosol product is chilled to a temperature of -25ºF and transferred to the test apparatus. The test liquid is allowed to increase slowly in temperature, and the temperature at which the vapors ignite is taken as the flash point more incase of hydrocarbon propellants.
Vapor Pressure: Measured by using a pressure gauge. If there is pressure variation from container to container is excessive, it indicates the pressure of air in the headspace.
Density: Accurately determined by using a hydrometer or pycnometer.
Moisture content: May be determined by using Karl Fisher or Gas Chromatographic methods.
Identification of propellants GC and IR Spectrophotometry are used to identify the propellant and also to indicate the proportion of each component in blend.
Aerosol Valve Discharge Rate This is determined by taking an aerosol product and weighing it initially. The contents are discharged for a given period of time using standard apparatus. The container is reweighed after a particular period of time. Change in weight per unit time gives the aerosol valve discharge rate usually expressed as grams per second.
Spray Pattern: Spray Pattern is determined and compared with the spray pattern obtained from different batches of material to ensure uniformity from batch to batch. Also spray pattern may be characteristic of the valve used. The method used to determine the pattern is based on the impingement of the spray on a piece of appear that has been treated with a bye-tale mixture. Depending on the nature of aerosol, an oil-soluble or water-soluble dye is used. The particles that strike the paper cause the dye to go into the solution and to be absorbed onto the paper. This gives a record of the spray, which can be used for comparison purposes. To control the amount of material coming into contact with the paper, the paper is attached to a rotating disk that has an adjustable slit which controls the amount of material that falls on the paper.
Dosage with Metered Valves
Points to be considered include:
1.Reproducibility of dosage each time the valve is depressed 2.Amount of medication actually received by the patient Reproducibility of dosage determined by dispensing one or more dosed into a solvent in which the drug is soluble. The solution of drug is then assayed and amount of active ingredients determined.
Another method that can be used to measure reproducibility involved accurate weighing of filled container, followed by dispensing of several doses. The container is then reweighed, and the difference in weight divided by the number of doses dispensed gives the average dose. This test must be repeated and results compared.
Determination of the dose actually received by patient is rather a difficult procedure, since all of the material dispensed is not carried out to the respiratory tract. An artificial system has been developed for this purpose.
Net Contents
Several methods have been developed to determine sufficient product has been placed into each container
1.The tarred cans are placed into the filling line, after being accurately weighed,difference in weight is equal to the net contents. 2.Another is a destructive method and consists of weighing a full container and then dispensing the contents. The container is reweighed after making provision for the amount of remaining material in the container, the net content in each container is determined.
Foam Stability
Various methods have been suggested for the determination of foam stability. The life of a foam can range from a few seconds (for some quick breaking foams) to one hour or more depending on the formulation.
Several methods have been used, which include a visual evaluation, time for a given mass to penetrate the foam, time for a given rod that is inserted into the foam to fall and use of rotational viscometers.
Particle Size Determination Many methods have been developed to determine the particle size among the methods; the most extensively used is the cascade impactor and ’light scatter decay’ methods. Cascade impactor operates on the principle that in a stream particles projected through a series of nozzles and glass slides at high velocity, the lager particles become impacted first on the lower velocity stages and the smaller particles pass on and are collected at higher velocity stages.
The figure showed, illustrates a unit suitable for the analysis of particles whose diameters range from 0.1 to 30 and is
specific for sampling aerosols comprised of particles that may be retained in the respiratory tract. Another method for
determining particle size is light scatter decay method. The principle behind the method is based on the change in light
intensity of a tyndall beam when the aerosol is sprayed into the beam of light.
Biological testing: Many biological tests have been used to evaluate the efficiency of many products, including various antibacterial agents. These tests on therapeutic efficacy and toxicity studies.
Therapeutic Efficacy or Activity: Various testing procedures are available to determine the therapeutic activity of aerosols. The procedures are similar to the non-aerosols. e.g. topical preparation are applied to the test areas and adsorption of therapeutic ingredients determined.
Toxicity: Toxicity testing should include both topical and inhalation effects. Aerosols applied topically may be irritating to the affected area and or may cause a chilling effect. The degree of chilling depends on the type and amount of propellant present. Inhalation toxicity must be considered even though the product may be intended for topical administration. This can be accomplished by exposing test animals to vapors sprayed from an aerosol container.
Dry Powder Inhalers
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