QUALITY CONTROL & EVALUATION OF PHARMACEUTICAL AEROSOLS
QUALITY CONTROL TESTS:- It includes the testing of:-
- Valves, Actuator, Dip Tubes
- Weight Checking
- Leak Testing
- Spray Testing
- Propellents:- All Propellents are accompanied by Specification sheet. Identification – Gas Chromatography Purity – Moisture, Halogen, Non-Volatile Residue Determination.
- Valves, Actuator, Dip-tubes: – Sampling is done according to standard procedure as found in Military Standards “MIL-STD-105D”.
For metered dose aerosols test methods was developed by ‘Aerosol Specification Committee’ ‘Industrial Pharmaceutical Technical Section ‘Academy Of Pharmaceutical Sciences. The object of this test is to determine magnitude of valve delivery & degree of uniformity between individual valves. Standard test solutions were proposed to rule out variation in valve delivery.
Testing Procedure:- Take 25 valves & placed on containers. Filled with specific test solution Actuator with 0.020-inch orifice is attached. Valve is actuated to fullest extent for 2 sec. Repeat this for total 2 individual delivery from each 25 test units.
Valve delivery per actuation in µL= Individual delivery wt in mg / Specific gravity of test sol.
54 µL or less – ± 15%
55 to 200 µL – ± 10%
Of 50 delivery
- If 4 or more are outside limits:- valves are rejected
- If 3 delivery are outside limits:- another 25 valves are tested : lot is rejected if more than 1 delivery outside specification
- If 2 delivery from 1 valve are beyond limits:- another 25 valves are tested : lot is rejected if more than 1 delivery outside specification
- Containers: – Containers are examined for defects in lining. Q.C aspects includes degree of conductivity of electric current as measure of exposed metals. Glass containers examined for Flaws.
- Weight Checking: – It is done by periodically adding tared empty aerosol container to filling lines which after filling with concentrate are removed & weighed. Same procedure is used for checking weight of Propellents.
- Leak Test:- It is done by measuring the Crimp’s dimension & comparing. Final testing of valve closure is done by passing filled containers through water bath.
- Spray Testing:- It is done for:
- To clear dip tube of pure propellant & concentrate,
- To check for defects in valves & spray pattern.
- Flammability & combustibility: –
- Flash point
- Flash Projection
- Physicochemical characteristics: –
- Vapor pressure
- Moisture content
- Identification of Propellents
- Aerosol valve discharge rate
- Spray pattern
- Dosage with metered valves
- Net contents
- Foam stability
- Particle size determination
- Biological testing:-
- Therapeutic activity
- Toxicity studies
- Flammability & combustibility:-
- Flash point:- Apparatus : Open Cup Tag Apparatus Test liquids temp. is allowed to increase slowly & temp. at which vapors Ignite is called as Flash Point .
- Flame Projection:- Product is sprayed for 4 sec onto flame & exact length is measured with ruler.
- Physicochemical characteristics:-
- Vapor Pressure:- By using Can Puncturing Device.
- Density:- By using Hydrometer, Pycnometer.
- Moisture:- By using Karl Fisher Method, Gas Chromatography.
- Identification:- By using Gas Chromatography, IR Spectroscopy.
- Aerosol valve discharge rate:- Aerosol product of known weight is discharged for specific time. By reweighing the container, the change in the wt. per time dispensed is the discharge rate in gm/sec.
- Spray pattern:- The method is based on the impingement of spray on piece of paper that has treated with Dye-Talc mixture.
- Dosage with metered valves:- Reproducibility of dosage determined by:
- Accurate weighing of filled container followed by dispensing several dosage. containers again reweighed & diff. in wt. divided by no. of dosage dispensed gives average dose.
- Net Contents:- Tared cans placed on filling lines are reweighed & then difference in wt. is equal to net content.
In Destructive method:- opening the container & removing as much of product possible.
- Foam stability:- Various Methods:-
- Visual Evaluation,
- Time for given mass to penetrate the foam,
- Time for given rod to fall which is inserted into the foam,
- Rotational Viscometer.
- Particle Size Determination:- Methods:-
- Cascade Impactor,
- Light Scattering Decay.
- a) Cascade Impactor:- Stream of particle projected through a series of nozzle & glass slides at high velocity, larger particle are impacted on low velocity stage , & smaller on higher velocity stage.
- b) Light Scattering Decay:- As aerosol settles under turbulent condition, the changes in the light of a Tyndall beam is measured.
- Biological testing:-
- For Inhalation Aerosols:- is depends on the particle size.
- For Topical Aerosols:- is applied to test areas & adsorption of therapeutic ingredient is determined.
- For Inhalation Aerosols:- exposing test animals to vapor sprayed from Aerosol container.
- For Topical Aerosols:- Irritation & Chilling effects are determined.
FIND MORE AT…