PHARMACEUTICAL AEROSOL : PHARMACEUTICAL AEROSOL AMIT M. GUPTA
AGNIHOTRI COLLEGE OF PHARMACY, WARDHA Definition : Amit M Gupta 2 Definition Packaging of therapeutic active ingredients in a pressurized system.
Aerosols are depends on the power of compressed or liquefied gas to expel the contents from containers. Advantages : Amit M Gupta 3 Advantages A dose can be removed with out contamination of materials. Stability is enhanced for these substances adversely affected by oxygen and or moisture. When sterility is an important factor, it can be maintained while a dose is being dispensed.
The medication can be delivered directly to the affected area in a desired form, such as spray, steam, quick breaking foam or stable foam.
Irritation produced by the mechanical application of topical medication is reduced or eliminated.
Ease of convenience of application.
Application of medication in thin layer Slide 4: Amit M Gupta 4 Components of aerosols
Valve and actuator
Product concentrate Slide 5: Amit M Gupta 5 Propellant
It is responsible for developing the power pressure with in the container and also expel the product when the valve is opened and in the atomization or foam production of the product.
# For oral and inhalation eg.
Dichlorodifluromethane (propellent 12)
Dichlorotetrafluromethane (propellent 114)
# Topical preparation
# Compound gases
Carbon di oxide
Nitrous oxide Slide 6: Amit M Gupta 6 Containers
They must be stand at pressure as high as 140 to 180 psig (pounds per sq. inch gauge) at 1300 F.
1. Tinplated steel
(a) Side-seam (three pieces)
(b) Two-piece or drawn
(c) Tin free steel
(b) One-piece (extruded or drawn)
3. Stainless steel
1. Uncoated glass
2. Plastic coated glass Slide 7: Amit M Gupta 7 Physiochemical properties of propellants
Liquid density Slide 8: Amit M Gupta 8 Vapor pressure of mixture of propellants is calculated by Doltan’s low which states that total Pressure in any system is equal to the sum of individual or partial pressure of various compounds
Raoult’s low regards lowering of the vapor pressure of a liquid by the addition of another substance, States that the dispersion of the vapor pressure of solvent upon the addition of solute is proportion to the mole fraction of solute molecules in solution.
The relationship can be shown mathematically :
pa = ------------ pAo =NApAo ----------(1)
na + nb
Where, pa = partial vaopr pressure of propellant A, pAo = vaopr pressure of pure propellant A
na = mole of propellant A, nb = mole of propellant B
NA = mole fraction of component A Slide 9: Amit M Gupta 9 To calculate the partial pressure of propellant B :
pb = ------------ pBo = NBpBo ----------(2)
nb + na
The total vapor pressure of system is then obtained as :
P = pa + pb ----------------------------------(3)
Where, P = total vapor pressure of system Slide 10: Amit M Gupta 10 Valves
To delivered the drug in desired form.
To give proper amount of medication.
Not differ from valve to valve of medication in pharmaceutical preparation.
- Continuous spray valve
- High speed production technique.
- Metering valves
Dispersing of potent medication at proper dispersion/ spray approximately 50 to 150 mg ±10 % of liquid materials at one time use of same valve. Slide 11: Amit M Gupta 11 Valve components
Ferrul or mount cap
Valve body or housing
Dip tube Slide 12: Amit M Gupta 12 Actuator
To ensure that aerosol product is delivered in the proper and desired form.
Different types of actuators
Solid steam actuators
Special actuators Slide 13: Amit M Gupta 13 Metered dose inhaler
To increased interest in modifying metered dose inhalers (MDIs) to minimize the number of administration error and to improve the drug delivery of aerosols particles into the drug delivery system of the nasal passageways and respiratory tract. Slide 14: Amit M Gupta 14 Formulation of pharmaceutical aerosols
Contains two essential components
Product concentrate contains ingredients or mixture of active ingredients and other such as solvents, antioxidants and surfactants.
May be single or blend of various propellants
Blends of propellant used in a p’ceutical formulation to achieve desired solubility characteristics or various surfactants are mixed to give the proper HLB value for emulsion system.
To give the desired vapor pressure, solubility & particle size. Slide 15: Amit M Gupta 15 Parameters consideration
Physical, chemical and p’ceutical properties of active ingredients.
Site of application Slide 16: Amit M Gupta 16 Types of system
Water based system
Suspension or Dispersion systems
1. Aqueous stable foams
2. Nonaqueous stable foams
3. Quick-breaking foams
4. Thermal foams
Intranasal aerosols Slide 17: Amit M Gupta 17 Manufacturing of Pharmaceutical Aerosols
Pressure filling apparatus
Cold filling apparatus
Compressed gas filling apparatus Slide 18: Amit M Gupta 18 Large scale equipment
Purger and crimper
Leak test tank Slide 19: Amit M Gupta 19 Quality control for pharmaceutical aerosols
Valves, actuator and dip tubes
Spray testing Slide 20: Amit M Gupta 20 Evaluation parameters of pharmaceutical aerosols
A. Flammability and combustibility
Flame extension, including flashback
B. Physiochemical characteristics
Identification of propellant(s)
Aerosol valve discharge rate
Dosage with metered valves
Particle size determination
D. Biologic characteristics
E. Therapeutic activity Slide 21: Amit M Gupta 21 Flame Projection
** This test indicates the effect of an aerosol formulation on the extension of an open flame.
** Product is sprayed for 4 sec. into flame.
** Depending on the nature of formulation, the fame is extended, and exact length was measured with ruler. Slide 22: Amit M Gupta 22 Flash point
Determined by using standard Tag Open Cap Apparatus.
Step involves are ?
Aerosol product is chilled to temperature of - 25 0 F and transferred to the test apparatus.
Temperature of test liquid increased slowly, and the temperature at which the vapors ignite is taken a flash point.
Calculated for flammable component, which in case of topical hydrocarbons. Slide 23: Amit M Gupta 23 Vapor pressure
Determined by pressure gauge
Variation in pressure indicates the presence of air in headspace.
A can punctuating device is available for accurately measuring vapor pressure. Slide 24: Amit M Gupta 24 Density
Determined by hydrometer or a pycnometer.
This method is use for non aerosol, modification to accommodate liquefied gas preparation.
Step involves are ?
A pressure tube is fitted with metal fingers and hoke valve, which allow for the introduction of liquids under pressure.
The hydrometer is placed in to the glass pressure tube.
Sufficient sample is introduced through the valve to cause the hydrometer to rise half way up the length of the tube.
The density can be read directly. Slide 25: Amit M Gupta 25 Moisture content
Method used — Karl Fischer method
G. C has also been used
Identification of propellants
Aerosol valve discharge rate
Determined by taking an aerosol known weight and discharging the contents for given time using standard apparatus.
By reweighing the container after time limit has expired, the change in weight per time dispensed is discharge rate,
Expressed as gram per seconds. Slide 26: Amit M Gupta 26 Dosage with metered valves
Reproducibility of dosage each time the valve is dispersed
Amt. of medication actually received by the patient.
Reproducibility has been determined by assay technique,
Another method is that, involves accurate weighing of filled container fallowed by dispersing of several doses, container can reweighed, and difference in weight divided by No. of dose, gives the average dosage. Slide 27: Amit M Gupta 27 Net contents
Filled full container, and dispensing the contents
Time for a given mass to penetrate the foam
Times for given rod that is inserted into the foam to fall
The use of rotational viscometers Slide 28: Amit M Gupta 28 Particle size determination
Light scatter decay method
Operates on the projected through a series of nozzle and glass slides at high viscosity, the large particles become impacted first on the lower velocity stages, and the smaller particals pass on and are collected at high velocity stages.
These practical ranging from 0.1 to 30 micron and retaining on RTI.
Modification made to improve efficacy Slide 29: Amit M Gupta 29 Porush, Thiel and Young used light scattering method to determine particle size.
As aerosols settle in turbulent condition , the change in light intensity of Tyndall beam is measured
Sciarra and Cutie developed method based on practical size distribution.