Evaluation of Aerosols

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Evaluation of Aerosols

9) Evaluation of Aerosols

9.1) Flammability and Combustibility

9.1 A) Flame Projection and flash back 9.1 B) Flash Point

9.2) Physico - Chemical Characteristics

9.2 A) Vapour Pressure

9.2 B) Density

9.2 C) Moisture Content

9.2 D) Identification of Propellant

9.2 E) Concentrate - Propellant ratio

9.3) Performance Test

9.3 A) Aerosol Valve Discharge Rate

9.3 B) Spray Patterns

9.3 C) Dose Uniformity / Dosage Testing with Metered valves

9.3 D) Net Contents

9.3 E) Foam stability

9.3 F) Particle Size determination

9.3 G) Leakage Test

9.4) Biological Testing

9.4 A) Therapeutic Activity

9.4 B) Toxicity

9.4 C) Extractable substances

Aerosols are pressurized packages and many tests are necessary to ensure proper performance of the package and safety during the use and storage. For the regulations of aerosols limitation on the pressure within the container, flash point, flame extension and flammability.

Pharmaceutical aerosols can be evaluated by testing physico-chemical, performance and biological tests.

9.1) Flammability and Combustibility

9.1 A) Flame Projection and flash back:

  • Flame test indicates the effect of an aerosol formulation on the extension of an open flame.
  • Aerosol product is sprayed for 4 sec. into open flame.
  • Depending on the nature and type of formulation, the fame is extended to some length and exact length was measured with ruler.

Flame projection test

9.1 B) Flash Point:

"Standard Tag Open Cap Apparatus" is used for determination of flash point.For this the formulation is chilled to temperature of -25 0F and transferred to the test apparatus. The temperature of test sample liquid increase slowly, and the temperature at which the vapors of propellant ignite is taken a "flash point". It is calculated for flammable component, which in case of topical hydrocarbon propellants.

Flash point

9.2) Physico - Chemical Characteristics

9.2 A) Vapour Pressure:

Vapour pressure is determined by pressure gauges or elaborately through use of a water bath, test gauges and other special equipments. Variation in pressure indicates the presence of air in headscape. Variation in pressure indicates the presence of air in the headscape. For accurate measurement of vapour pressure in aerosol container can punctuating device used.

9.2 B) Density of aerosol system:

  • It is determined by hydrometer or a pycnometer.
  • This method is useful for non aerosols modification to accommodate the liquefied gas preparation.
  • In which a pressure tube is fitted with metal fingers and hoke valve of apparatus, which under pressure the liquids are introduced.
  • The hydrometer is kept in to the glass pressure tube. Some sufficient amount of sample is added through the valve to cause the hydrometer to rise half way up the length of the tube. The density can be read directly from the apparatus.

Pycno meter

Hydro meter

9.2 C) Moisture Content:

Karl Fischer method or Gas chromatography method used.

Karl fischer

9.2 D) Identification of Propellant/s:

Gas chromatography or I.R spectrophotometry methods are used for identification of propellants and also to indicate the proportion of the each component in a blend.

9.2 E) Product Concentrate - Propellant ratio:

The proportion of the each component in a blend can be determined by Gas chromatography or I.R spectrophotometry methods are used.

Summary of physicochemical characteristics of Aerosols:

Pyhysico-Chemical Characteristics

Equipments for measurement

Vapour pressure

Can Punching device

Pressure Gauge

Density

Hydrometer

Pycnometer

Moisture content

Karl Fischer method

Gas Chromatography

Identification of propellant/s

Gas Chromatography

IR Spectrometry

9.3) Performance Test

9.3 A) Aerosol Valve Discharge Rate:

It is determined by taking an aerosol with known weight and discharging the contents for given time using standard apparatus. Again reweigh the container, the difference in weight per time release or dispensed is discharge rate. It is expressed as gram per seconds.

9.3 B) Spray Patterns:

For this, the method involves the impingement of sprays on a piece of paper, which is treated with dye - talc mixture. Based on the nature and type of the aerosol, an oil soluble dye or water soluble dye is used. When the particles reach the paper it causes the dye to go into solution and to be absorbed onto the paper. It gives a record of the spray pattern.

Spray patterns

9.3 C) Dose Uniformity / Dosage Testing with Metered valves:

Several points to be considered 1) Reproducibility of dosage each time the valve is dispersed and Amount of medication actually received by the patient.

Reproducibility has been determined by assay technique and amount of active ingredient is determined. Another method for determination of active ingredient that accurate weighing of filled container then remove contents by dispersing and reweigh the container can and difference in weight divided by Number of doses, gives the average dosage.

9.3 D) Net Contents:

Weight method used. The tared cans are placed on to the filling line and weighed; the difference in weight is equal to the net contents.

Te other method is a Destructive method and consists of weighing of a full container, and dispensing the contents. The contents are then reweighed. The difference in weight gives the amount of contents present in the container.

9.3 E) Foam stability:

The life of a foam ranges from a few seconds (for quick breaking foam) to one hour or more depending on the formulation and type of foam.

The methods used to determine the foam stability is Visual evaluation. Visual evaluation is the

time for a given mass to penetrate the foam, time for given rod that is inserted into the foam to fall.

9.3 F) Particle Size determination:

Particle size can be determined by Cascade impactor and Light scattering decay methods.

Cascade impactor:

Cascade impactor works on the projected through a series of nozzle and glass slides at high velocity. First the larger particles become impacted on the lower velocity stages and then the smaller particles impacted at high velocity stages. The size ranges from 0.1 to 30 u (microns).

Cascade Impactor1

Cascade Impactor

Light scattering decay:

Light scattering method is used to determine the particle size. The aerosol product settle in turbulent condition, Here the particle size is measured by the change in light intensity of Tyndall beam.

Light Scattering Decay

9.3 G) Leakage Test:

Leak test is done by checking the crimping of the valve must be available to prevent defective containers. This is accomplished by measuring the crimp's dimension and ensuring that they meet specifications. Final testing of valve closure is done by passing filled containers through water bath.

9.4) Biological Testing

The final phase of testing of aerosols involved in a comprehensive research and development program for pharmaceutical aerosols must involve biological testing. These are similar to tests performed for non aerosol pharmaceuticals.

9.4 A) Therapeutic Activity:

For Inhalation Aerosols: Therapeutic activity is depends on the particle size.

For Topical Aerosols: It is determined by applying the active ingredients topically to test areas and the amount of therapeutic active ingredients absorbed is determined.

9.4 B) Toxicity:

For Inhalation Aerosols: Inhalation toxicity is studied by exposing test animals to vapor sprayed from Aerosol container.

For Topical Aerosols: Irritation on the skin & chilling effects are checked. When aerosol is topically applied, thermistor is used to determine the change in skin temperature for a given period of time.

9.4 C) Extractable substances:

The pressurized inhalers and aerosols are normally formulated with organic solvents as the propellant or the vehicle. The leaching of extractables from the elastomeric and plastic components into the formulation is a potentially serious problem.

So, the composition and the quality of materials used in the manufacture of the valve components (e.g., stem, gaskets, housing, container etc.) must be carefully selected and controlled. The container compatibility with formulation components should be thoroughly checked, so as to prevent distortion of the valve components and to minimize changes in the medication delivery, discharge rate, leaks and impurity profile of the drug product over time.

The extractables profiles of a representative sample of each of the elastomeric and plastic components of the valve should be established under specified conditions and should be correlated to the extractable profile of the placebo or aged drug product, to ensure quality and purity of the drug product. Extractable substance which may include poly nuclear aromatics, nitrosamines, antioxidants, plasticizers, vulcanization accelerators and monomers, etc., should be identified and minimized wherever possible.

Depends on the specifications and limits for individual components and total extractables from different valve components may require the use of different analytical methods.

About the Author

Naseeb Basha Shaik's picture

Working as Assistant Professor, Pharmaceutics Department at G.Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad.

Comments

Eswar GsnkRao's picture

VERY LUCID EXPLANATION, Good.

Diagramatic based explanation is appreciable. Students can now easily understand the tests. Both theoretically and competitively Evaluation tests of Aerosols are very important. Hope students will make use of this book page.

Regards

ESWAR :-) 

Naseeb Basha Shaik's picture

Thank You and Hope so Students will utilise this Aerosols Book page.

Naseeb Basha Shaik

Assistant Professor

G. Pula Reddy College of Pharmacy, Hyderabad-28.

Ph. Bhagavan P S RPh's picture

There are many new dosage forms that have and have been comming into market. It would be a good idea to get samples of all those, cut them to show the students how they are structured and function?

Similarly the students should know how Child lock or proof closures work.

I remember when I used to collect coated and layered tablets and spansules to see how they have been placed and separated while I was a student.

Bhagavan P.S. B Pharm

Rtd. Dy Dir.(Pharmacy),Govt of Karnataka, India
Ph. Bhagavan P S RPh's picture

Dear Dr Naseeb Basha Shaik, Thanks for the pains you have taken in giving out so much of information on less known but bastly used product. I wish I had break open an aerosol to see its structure. Any way I will try on one of each type.

I look forward for such structural and functional disclosure

Thank you again, Thank you

Bhagavan P.S. B Pharm

Rtd. Dy Dir.(Pharmacy),Govt of Karnataka, India
Naseeb Basha Shaik's picture

Thank you sir

Naseeb Basha Shaik

Assistant Professor

G. Pula Reddy College of Pharmacy, Hyderabad-28.

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