BY

Dr. Muhammad Akbar (Pharm.D), U.O.P, R.Ph M.Phil Scholar

Definition
Aerosols are pressurized dosage forms

containing one or more active drug dissolved, suspended, or emulsified in a propellant or a mixture of solvent and propellant, which is released on actuation of the valve as a fine dispersion of liquid or solid in a gaseous medium.

 Used for either topical, oral or nasal

administration in the form fine particles or mist or fog. Mainly used for the treatment of Asthma and COPD disease. Designed to expel their contents as a fine mist, a coarse wet or dry spray, a steady stream or a stable or fast breaking foam.

Advantages
A dose

can be removed with out contamination of materials. 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.

Advantages
Prevents Oxidation of drugs
Maintain sterility Ease of convenience of application. Application of medication in thin layer

Types Of Aerosol Spray

There are three types of aerosol spray. Space sprays: They deliver product as a fine mist.

Particle size is not more than 50m eg. Room sprays Surface coating spray: Aerosols intended for carrying active ingredients to surface are termed as surface sprays or surface coating spray. eg. Topical Aerosol Foam spray: Spray ingredients in the form of foam e.g Shaving foam

Components Of Aerosols
Aerosol consist of 1. Product concentrate 2. Propellant 3. Container 4. Valve and actuator
Actuator

Valve

container

Product concentrate
consist of API, additives like suspending agent , emulsifying agent,antioxidant, aqeous and non aqueous sovents, cosolvent etc

Propellant
It is responsible for developing the vapour

pressure with in the container and also expel the product when the valve is opened and helps in the atomization or foam production of the product. It is classified in to mainly two types
1. Liquified gas system 2. Compressed gas system

Liquified gas system

These compounds are gases at room temperature and atmospheric pressure. However they can be liquified easily by lowering the temperature or by increasing pressure. These compounds generally have B.P below 70o 0F and vapour pressure between 14 and 85 psia at 70o 0F. When it is placed into sealed container it

immediately separartes into a liquid and a vapour phase

Examples
CHLORO FLURO CARBON( CFC): Advantages are Low inhalation toxicity High chemical stability High purity Disadvantages are Destructive to atmospheric Ozone High cost Trichloromonofloromethane CCl3F Dichlorodifloromethane CCl2F2 Dichlorotetrafluromethane CClF2 CClF2 etc HYDROCARBONS: Chemically stable Inflammable

Low toxicity.They are lighter than water

Compressed gas system

They have widespread use in aerosols for oral and inhalation

use. HC and compressed gas find widespread use in aerosols for topical use. High chemical stability High purity Inexpensive No environmental problems Produce course droplet sprays Pressure falls during use Examples are: CO2 , NO, N2 FHC

 For oral and inhalation Fluorinated hydrocarbons Dichlorodifluromethane (propellent 12) Dichlorotetrafluromethane (propellent 114) Topical preparation Propane Butane Isobutane Compound gases Nitrogen Carbon di oxide Nitrous oxide

Aerosol Principle
Liquified gas propellant + Product concentrate Equilibrium is established (b/w portion of liqified

propllent and which vaporizes and occupies the upper portion of aerosol container) The vapour phase exerts pressure and this pressure upon actuation of the areosol valve forces the liquid phase up the diptube and out of the orifice of the valve into the atmosphere Propllent meets the air , it expands and evaporates because of drop in pressure , leaving the product concentrate as airborne liquid droplets or dry partticles

Aerosol Container
Containers must withstand pressure as high as 140 to 180

psig. Different types of containers are used which are: 1. Metals

Tin plated steel b) Aluminium c) Stainless steel
a)

2. Glass a. Uncoated glass b. Plastic coated glass 3. Plastic

Valve Assembly
To delivered the drug in desired form. To give proper amount of medication. Not differ from valve to valve of medication in

pharmaceutical preparation.

Types:

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.

Valve components
Ferrul or mount cap

Valve body or housing

Stem Gasket Spring Dip tube

Actuator
To ensure that aerosol

product is delivered in the proper and desired form.

Different actuators

types

of

Spray actuators Foam actuators Solid steam actuators Special actuators

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.

Types of Aerosol System

Two phase system
Three phase system

Two Phase System

Consists of two phases i.e Liquid phase & Vapor phase
Active ingredients soluble in the propllent so no other

solvent is required.

Three Phase System

Three phase system consists of:
A layer of water- immisible liquid propellent A layer of highly aqueous product concentrate

A vapour phase

Ethanol is used as cosolvent in these systems. Surfactants (0.5-2%) are added for homogenous dispersion.

Manufacturing of Pharmaceutical Aerosol

Cold filling apparatus

Pressure filling apparatus

Compressed gas filling apparatus

Pressure Filling
Pressure filling is carried out at R.T. under high

pressure. The apparatus consists of a pressure burette capable of metering small volumes of liquefied gas under pressure into an aerosol container. The propellant is added through the inlet valve located at the bottom or top of the burette. The desired amount of propellant is allowed to flow through the aerosol valve into the container under its own vapor pressure. When the pressure is equalized between the burette and the container (thus happens with low pressure propellant), the propellant stops flowing.

Advantages
It is the preferred method for solutions, emulsions and

suspension. Less chances for contamination of product with the moisture. Less propellant is lost No refrigeration is required, can be carried out at RT

Cold Filling Process

The principle of cold filling method requires

the chilling of all components including concentrate and propellant to a temperature of 30 to -40 F. This temprature is necessary to liquify the propellant gas. The cooling system may be a mixture of dry ice and acetone or refergiration system. First, the product concentrate is chilled and filled into already chilled container followed by the chilled liquefied propellant

 Advantages
Easy process

Disadvantages
Aqueous products, emulsions and those products

adversely affected by cold temperature cannot be filled by this method. For nonaqueous systems, some moisture usually appear in the final product due to condensation of atmospheric presure

Compressed Filling
Compressed gases are present under high pressure in

cylinders. These cylinders are fitted with a pressure reducing valve and a delivery gauge. The concentrate is placed in the container The valve is crimped in place Air is evacuated by means of vacuum pump The filling head is inserted into the valve opening, valve depressed and gas is allowed to flow into the container For those products requiring an increased amount of gas or those in which the solubility of gas in the product is necessary, carbon dioxide and nitrous oxide can be used. To obtain maximum solubility of the gas in the product, the container is shaken manually during and after the filling operation by mechanical shakers.