Manufacturing of Pharmaceutical Aerosol

Table of Contents

Formulation of Aerosol

Formulation of Aerosol consists of two important components

Product concentration (Active Ingredient, Other necessary agents such as solvents, surfactants, antioxidants etc)
Propellants (Single or blend of diffent propellants)

Type of aerosol system

There are three type aerosol system.

a) Solution system/two-phase system:

It consists of vapour phase and liquid phase. Volatile substance may lower the vapour pressure of propellant. amount of propellant is about 5%(for Foam) to 95%(for Inhalant).

b) Water-based system/three-phase system

Water is used to replace all or part of non-aqueous solvent used in an aerosol.

Also referred to as water-based aerosol. propellant concentration is about 25 to 60%.

The active ingredients are formulated as an emulsion system ( propellant is in the external phase).
When a product is dispensed the propellant (external phase) vaporizers and dispersion the active ingredient into minute droplet/particles.

Water and propellant are immiscible, Three-phase aerosol- Propellant phase, water phase and vapour phase.

c)Aquasol system

It is essentially a three-phase aerosol permits the use of a large quantity of water in the formulation.
The ratio of hydrocarbon and water: 1:6.

Manufacturing of Aerosol

Equipment Used for the manufacturing of Aerosol includes

Mixing Equipment
Filling Machine (Cold filling Machine, Pressure Filling Machine, Compressed Gas Filling, Rotary Filling Machine)
Sealing Machine
Labeling & Packaging

MANUFACTURING OF PHARMACEUTICAL AEROSOLS includes three techniques

1. Pressure filling apparatus

2. Cold filling apparatus

3. Compressed gas filling apparatus

4. Rotary Filling Machine Method

1. Pressure filling apparatus

It consists of a pressure burette capable of metering small volumes of liquefied gas into the aerosol container under pressure.
Propellant is added through an inlet valve located at the bottom or top of the pressure burette.
The propellant is allowed to flow with its own vapor pressure in the container through aerosol valve.
The trapped air escapes out from the upper valve.
The propellant stops flowing when the pressure of burette and container becomes equal.
If further propellant is to be added, a hose (rubber pipe) leading to a cylinder of nitrogen is attached to the upper valve, the pressure exerted by nitrogen helps in the flow of the propellant into the container.
Another pressure filling device makes use of piston arrangement and is capable of maintaining positive pressure .
This type of device cannot be used for filling inhalation aerosols which have metered valves.

PROCEDURE:

This method involves filling of the concentrate into the container at the room temperature.
Then the valve is placed in the container and crimped.
Through the opening of the valve the propellant are added or it can be added “under the cap”.
Since the opening of the valve are smaller in size ranging from 0.018-0.030 inches, it limits the production and the process becomes slow.
But with the use of rotary filling machines and newer filling heads where the propellants are filled through valve stem, the production rate is increased.
The trapped air in the container and air present in head space is removed before filling the propellant to protect the products from getting adversely affected.
Various units used in pressure filling line are arranged in the following order :
Unscrambler , Air cleaner , Concentrate filler , Valve placer , Purger , Valve crimper , Propellant filler ,Water bath , Labeler , Coder and Packing table .
Purger ,vacuum crimper and pressure filler are replaced with a single unit if the filling is carried by ‘under the cap’ method.

ADVANTAGES OF PRESSURE FILLING:

Solutions, emulsions, suspensions can be filled by this method as chilling does not occur.
Contamination due to moisture is less.
High production speed can be achieved.
Loss of propellant is less.

DISADVANTAGES :

Certain types of metering valves can be handled only by the cold filling process or through use of an under the cap filler and valve crimper.
Process is slower than Cold filling method.

2. Cold filling apparatus

•It consist of an insulated box fitted with copper tubings and the tubings are coiled to increase the area exposed to cooling.
• The insulated box should be filled with dry ice or acetone prior to use.
• The apparatus can be operated with or without metered valves.
• Hydrocarbon propellant cannot be filled into aerosol containers using this apparatus because large amount of propellant escapes out and vaporizes.
• This may lead to formation of an explosive mixture .
• Fluorocarbon vapors do not form any explosive or flammable mixture though their vapors are heavier than air.
PROCEDURE:
• Non aqueous products and products which can withstand low temperatures of – 40°F are used in this method.
• The product concentrate is chilled to a temperature of – 40°F and filled into already chilled container.
• Then the chilled propellant is added completely in 1 or 2 stages, depending on the amount.
• Another method is to chill both the product concentrate and propellant in a separate pressure vessel to – 40 °F and then filling them into the container.
• The valve is placed and crimped on to the container.
• Then test for leakage and strength of container is carried out by passing container into a heated water bath, where the contents of the container are heated to 130°F. After this, the containers are air dried , capped and labeled.
Various units used in cold filling methods are : Unscrambler, Air cleaner ,Concentrate filler ,Propellant filler ,Valve placer ,Valve crimper ,Water bath ,Labeler, Coder and Packing table .

• The cold filling method is no longer being used, as it has been replaced by pressure filling method.

Advantage:

• Easy process.

Disadvantages :

• Aqueous products, emulsions and those products adversely affected by cold temperature cannot be filled by this method.

3. Compressed gas filling apparatus

Compressed gases have high pressure hence a pressure-reducing valve is required.

• The apparatus consists of delivery gauge.
• A flexible hose pipe which can withstand 150 pounds per square inch gauge pressure is attached to the delivery gauge along with the filling head.
• A flow indicator is also present in specialized equipments.
PROCEDURE :
• The product concentrate is filled into the container.
• Valve is placed and crimped on the container.
• With the help of vacuum pump the air is removed from the container.
• Filling head is put in the opening of the valve and the valve is depressed and the gas is allowed to flow in to container.
• The gas stops flowing if the delivery pressure and the pressure within the container become equal.
• Carbon dioxide and nitrous oxide is used if more amount of gas is required.
• High solubility of the gas in the product can be achieved by shaking the container manually or with the help of mechanical shakers.