1. Aerosols
Dr. Akhilesh Gupta

2. Aerosols
Aerosols are pressurized dosage form, containing one or more active ingredients, which upon actuation emit a fine description of liquid and solid materials in gaseous medium.
Pressure is applied to the aerosol system through the use of one or more liquefied or gaseous propellants upon activation of value assemble of aerosol. It is the pressure exerted by the propellant which forces the contents of the package out through opening of the valve.

3. There are 3 types of aerosols:
1. Space spray: Product dispersion o particles which remain in the air for prolonged periods. the particles of spray are usually less than 50µm in size .
2. Surface coating spray product a film on the surface treated this type of aerosol is relatively coarse. The particles range in size from 50to200µm.
3. Foams are formed when expansion of propellant within an emulsion results in production in small bubbles.

4. Aerosols components: 4 main component of an aerosol system is
1. the propellant the container
3. Value & actuator Active ingredient concentrate
The propellant: The function of the propellant in an aerosol system is to produce pressure to expell the medicament.

5. The propellant sometimes also acts as solvent for active substance.
Liquefied gas propellant compressed gas propellant
Hydrocarbons chlorofluorohydrocarbons
Chlorofluorohydrocarbons (CFC) propellant:
* Trichloromonofluoromethane (011)
*Dichlorodifluoromethane (012)
* Dichlorotrtrafluoro methane (114)
*Responsible for depletion of ozone layer of atmosphere hence their use has declined in recent time. But still widely inside in pharma preparation.

6. Naming of CFC:
The first digit represent the number of carbon minus one, i.e.,(nC-1)
Second digit represent the number of Hydrogen plus one, i .e. (nH+1)
Third digit represent the number of fluorine atoms.
So first digit will be (nC-1), i.e.,
2-1=1
Number of hydrogen is 4
So the second digit will be
(n4+1)4+1=5
Number of fluorine is 2
Third digit will be 2
Number of propellant will be 152.

7. Hydrocarbon propellant
The most commonly use hydrocarbon propellants are n-butane, isobutane and propane. They are usually blended to obtain properties.
Advantages:
(a) Hydrocarbon propellant have ability to dissolve large no. of medicament
(b) they are physically & chemically stable
(c) They lack odour , have low cost &low toxicity
(d) Immiscible with water ,gives three phase system.

8. Compressed gas propellant:
These include nitrous oxide, carbon dioxide ,nitrogen.
The pressure within a aerosol container filled with liquefied gases remains constant because as propellant is lost through actuation more vapour is formed within container & equilibrium is reestablished. The vapour pressure is therefore independent of liquefied gas used.
In compressed gas system as the concentration is expelled from the container, the head space increase &gave expand causing a decrease in pressure.

9. Mechanism of deposition of inhalation aerosols I respiratory tract: Inertial impaction - depotion in upper airways or particles having aerodynamic diameter DA Upto 15µm (mouth breathing) 10µm (nasal breathing ) Sedimentation - deposition in the airways For particles having aerodynamic diameter DA (0.5 µm < DA <3µm) Diffusion or - diffusion from the aerosol cloud to the walls of respiratory tract Brownian motion - for deposition of particles having DA <0.5µm. Interception - for deposition of elongated particles in lower airways. Electrostatic - precipitation of charged aerosol particles by Precipitation attraction of oppositely charged respiratory wall.

10. AEROOL SYSTEM
Liquefied gas system –
Two phase system or solution system:
The simplest aerosol system is the two phase or solution system in which the drug is soluble in propellant or drug is dissolved which is miscible with propellant to as to produce solution system. It consist only of a vapour phase and liquid phase (solution of active ingredient in liquid propellant)

11. When some of the components of an aerosol are immiscible with or insoluble in the liquefied propellant a three phase system results
The non vapour phase can be suspension or emulsion.
The three phases are usually:
(a) An aq. Solution of active ingredient
(b) the liquid propellant
(c) the vaporized propellant
CFC propellant in three phase system lies beneath the aqueous layer whereas hydrocarbon propellant lies above the water phase.
The dip tube of the container must reach upto the aqueous phases . when the value is opened the pressure of vapour force the aqueous liquid up the tube no propellant escapes. as no propellant is emitted to break up the doplet a mechanical break up actuator is required to reduced the size of droplet .
The emulsion aerosol can be dispensed as quick breaking or stable from.
In stable from the propellant in the concentration of 3-5% is made the internal phase where as in quick breaking from propellant is the external phase.
Valves
Continuous spray valve metered dose valve

12. Continuous spray valve has following components :
(A) ferrule or mounting cap to attach valve to container
(B) valve housing opening between to 0.20 cm at point of attachment to dip tube.
(C) Gasket to provide a seal between valve and container.
(D) Spring helps to return the valve to the closed position of after actuation.
(E) Dip tube made upto of polyethylene or having diameter between 3 to 3.2 mm. Its bring formulation from container upto value.
(F) Stem: when stem is pressed the product is emitted from the container.

13. Actuator: actuator allow for easy opening and closing of the valve
Actuator: actuator allow for easy opening and closing of the valve. The design of actuator determines whether spray foam or solid stream is produced.
To produce spray aerosol mechanical break up actuator are use . In this, channels in the actuator cause the stream to breakup into a spray.
Foam actuators have large chamber where the product expands before release . semisolids are delivered using actuator whit large orifice

14. MANUFACTURE OF AEROSOL:
Preparation o the product concentrate is similar to preparation of any equivalent pharmaceutical preparation. The major difference arises in case of packaging.
There are two modes of filing-
(1)Cold filling:
Low temp range -340C to -400C required for filing process.
The product concentrate is chilled and added to open container followed by chilled propellant. Or the concentrate and propellant can be chilled together and mixture added to container.
A valve is then crimped into places.
Container into placed through a heated test bath as a checked for leakage and container strength.
This method is not suitable for aqueous products or for preparation that are adversely affected by low temperatures.

15. (2) Pressure filling : (a)(Method One: The product concentrate is added to container at room temperature The valve crimped into place. The propellant is then added under pressure through the valve stern or through the actuator and around the sealing gaskets. (b)Method two UNDER THE CAP METHOD: product concentrate is added to container and valve placed position . a seal is formed around the shoulder of the container and using a vacuum , the valve cup is raised slightly from The can and propellant is added. The valve is then crimped into place. Pressure filling can be used for all types of aerosols.

16. Container for aerosols:-
Material used for aerosol container include
Tin pated steel
Aluminum
Stainless steel
Glass
Plastic
Choice of material depends on:-
1. Pressure of the system
2. Whether product is aqueous or not
3. pH of the product
4. Physico chemical prosperities o the preparation

17. A] Tin plated steel: It is used or the most aerosol as it is light inexpensive and durable. It is steel that has been placed on he both side with tin.
Tin plated steel containers are of two types:-
1. Two pieces container body, Consisting of a drawn cylinder, the base of the container is held in place with double seam.
2. The three pieces container has a side seam the base being attached as for two piece container, the top has a 1 inch opening and is joined to body by double seaming.
B] Stainless steel:- It is resistant to corrosion and no coating is required. It can withstand high pressure. However they are expensive.

18. C] Aluminum:- Aluminum container are more resistant to corrosion than tin plated steel. Aluminum containers are made by an extrusion process and hence have no seam. Aluminum is subjected to corrosion by water and alcohol. D] Glass: containers are obtained coated with plastic. The coating gives protection from impact Glass has advantage of being transparent so content can be viewed. Glass is virtually inert. E] Plastic:- Not widely used for aerosol container polyethylene tetraphthalate (PET) containers are used for some non pharmaceutical products.

19. EVALUATION O THE AEROSOL Particle Size determination: A] Microscopy: the aerosol is actuated on a glass slide after priming of the valve and the slide raised with carbon tetrachloride avoiding loss of particulate matter. The side is allowed to dry and examine under microscope. B] cascade impaction:- A cascade impactor is capable of measuring particles size range, 0.2 to 20 µ m (micro meter). The aerosol passes through a series of the nozzles of decreasing diameter under vacuum. After each stage there is a glass slide coated with viscous fluid. The remaining particles pass through yet another nozzle . the size distribution of the aerosol can then be determined. C] Light scattering Methods: Light scatterings method can measure particles in the size range of 0.1 to 20 micrometer. They can utilize either wide light or laser light and work on the principle that particles suspended in ear will cause a scattering of light which can b monitored by a photo detector.

20. Physicochemical Properties: (a) Vapor pressure: vapour pressure are measured by a gauges that has been calibrated to pressure of the system by water bath test or by container puncturing device. (b) Density: density of the aerosol system is measured by hydrometer and pycnometer. (c) Moisture content: moisture is determined by Karl Fisher method. Aerosol Performance Test: These includes (a) Measuring content of the container usually by weighing before and after filling. (b) Passing filled container through a water bath to check the leakage in container (c) Rate of discharge through the valve. (d) Pattern of the spray.

21. Specific test for metered dose aerosol: Quality of the active ingredient delivered by a metered –dose valve is determined by discharge the aerosol into solvent and assaying the resulting solution. The number of deliveries is measured simply by actuating the valve at interval o not less than 5 seconds until the container is spent. The number of deliveries should not be less than that stated on label.