FORMULATION AND MANUFACTURING OF AEROSOL

Submitted by

Ranjeet Kumar M.Pharm 2nd semester Roll No:02

INTRODUCTION
Aerosol is defined as a system that depends on the power of a compressed or liquefied gas to expel the contents from the container. It is also known as canister/pressure package/pressurized package. In mid 1950 the pharmaceutical aerosol introduced in market.

ADVANTAGES
Convenience, speed & ease of application. It can avoid the hepatic metabolism of drugs. Avoidance of manual contact with medicament Controlled & uniform dosage delivered by metered valves. Absence of air in container prevents oxidation of susceptible drugs. It directly applied to the affected area in a desired foam. It produce local & systemic effect(due to large surface area of lung and blood capillary )

Disadvantages:
Costlier than traditional pack. Disposal may difficult. Pack should not be subjected to heat. If the drug is not soluble in propellant formulation difficulties arised. There may be propellant toxicity when inhalation therapy last for a long period. Heart patient may be at risk if propellants are inhaled. Some propellants (CFCS) cause environmental problem.

COMPONENT OF AEROSOL

1. Product concentrate 2. Propellant 3.Container 4.Valve and actuator

AEROSOL CONTAINERS
Containers used for manufacturing of aerosol must withstand pressure as high as 140 to 180psig Types of containers: 1. Tin plate containers consists of sheet of steel plate that has been electroplated on both sides with tin 2. Aluminum containers Greater resistance to corrosion, Lightweight, not fragile Good for light sensitive drugs

Contd
3.Stainless steel container Limited for smaller size Extremely strong and resistant to most materials Pressure stand 4. Glass containers Available with plastic or without plastic coating Compatible with many additives No corrosion problems Can have various shape because of molding Fragile Not for light sensitive drugs

COMPONENT OF AEROSOLS
Actuator Ferrule or mount cap Valve body or housing Stem Gasket Spring Dip tube

TYPES OF ACTUATOR
Actuators: These are specially designed button placed on the valve system which helps in easy opening and closing of the valve. It helps in deliver the product in the desired form. There are different type of actuators are used , Spray Actuators-orifices 0.016- 0.040inch. Foam Actuators-orifice diameter 0.070-0.125 inch Special Actuators-to deliver the medicament on the specific sites

VALVES
Regulate the flow of product and discharge the content. Valve is associated with the help of actuautor (if the foam present in the container) to emitted the product as wet or spray TYPES OF AEROSOL VALVES 1.Continuous spray valve Mounting Cup / Ferrule, Valve body or Housing Stem , Gasket, Spring, Dip Tube 2. Metering valve

Formulation of Aerosol
An Aerosol formulation consists of three essential components : Propellant Product concentrate Types of system Parameters consideration : Physical ,chemical and pharmacological properties of active ingredient, surfactant, solvent to give the proper HLB value for an emulsion. Propellant is selected to give the desired vapour pressure, solubility, and particle size. Types of system required to dispensed as fine mist, wet spray, foam.

TYPES OF AEROSOL SYSTEM

There are five types of aerosol system 1.Solution system / Two phase system 2.Water based system / Three phase system 3.Suspension or Dispersion system 4.Foam system Aqueous stable foam Non-Aqueous stable foam Quick Breaking Foam Thermal foam 5.Intranasal foam

SOLUTION SYSTEM
Which consists of two phases: a vapour phase and liquid phase. When the active ingredients are soluble in the propellant, no other solvent is required. Depending on the type of spray required Propellant are used.

WATER BASED SYSTEM

These are applicable for those drug which is not soluble in propellant. Since water and propellant are not miscible so It form three phase system containing vapour phase, propellant , water. Ethanol used as a cosolvent to solubilise the propellant in water. It is difficult to achieve desired fine particle size with product containig large amounts of water and low proportion of propellant, a mechanical breakup actuator must be used along with a vapour tape valve.

SUSPENSION SYSTEM
To overcome the difficulties arises from water based system or addition of cosolvent suspension system is used. It is prepared by dispersing active ingredients in mixture of propellant by using suspending agent. The physical stability of suspension can be increased by using minimum solubility of API. Eg. Ephedrine bitartarate is less soluble than Hcl. By Use of surfactant to reduce the agglomeration Eg. Sorbitan monolaurate ,sorbitan monooleate, sorbitan trioleate, isopropyl myristae.

FOAM SYSTEM
They contain Dispersion of A.I, Aqueous or nonaqueous Vehicle, surfactant and propellant. Liquefied propellant is emulsified and found in the internal phase. Aqueous stable foam A. Ingredients oil waxes O/W surfactant Water Hydrocarbon Non aqueous stable foam : These are prepared by using Glycols Emulsifying agent used this type PEG Esters

FOAM SYSTEM
Quick breaking foam : In this system the propellant is in the external phase. when dispensed, the product is emitted as a foam which then collapsed in to liquid. Useful for topical medication. Thermal foam : Used to produce a warm foam for shaving.

Preparation of product concentrate

The aerosol concentrate consists of drug or combination of drugs, solvents, antioxidants and surfactants formulated as solution, suspension . The aerosol concentrate is first prepared and filled into the container. The propellant is then filled into the container. Therefore, part of the manufacturing operation takes place during the filling operation measures to ensure that both concentrate and propellant are brought together in the proper proportion.

MANUFACTURING OF PHARMACEUTICAL AEROSOL

Apparatus Cold filling process Pressure filling process Compressed gas filling process Automatic filling process

COLD FILLING APPARATUS

Hoke valve

Cooling chamber

VALVE CRIMPER
Evacuate the air and seal the valve in place

COLD FILLING PROCESS

Single head or multiple head rotary unit capable of vacuum crimping up to 120 can / min are available. A valve is placed either manually or automatically depending on the production rate required. The valve is crimped in place by using valve crimper. Disadvantages Aqueous products, emulsions and those products adversely affected by cold temperature cannot be filled by this method.

PRESSURE FILLING MACHINE

ADVANTAGES
It is the preferred method for solutions, emulsions and suspension. Less chances for contamination of product with the moisture. No refrigeration is required, can be carried out at RT.
DISADVANTAGES Not suitable for inhalation aerosol fited with metered valve

COMPRESSED FILLING
Compressed gases are present under high pressure in cylinders. These cylinders are fitted with a pressure reducing valve and a delivery gauge. 1.The concentrate is placed in the container 2.The valve is crimped in place 3.Air is evacuated by means of vacuum pump 4.The filling head is inserted into the valve opening, valve depressed and gas is allowed to flow into the container 5.To obtain maximum solubility of the gas in the product, the container is shaken manually during and after the filling operation by mechanical shakers.

Automatic Aerosol Sealing and Propellant Filling Machine

Automatic-Aerosol-Filling-Machine

Automatic Aerosol Sealing and Propellant Filling Machine

video

Evaluation of pharmaceutical aerosols

FLAME PROJECTION TEST 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 flame is extended, and exact length was measured with ruler.

FLASH POINT
Determined by using standard Tag Open Cup Apparatus. PROCEDURE:
Aerosol product is chilled to temperature of 25 F and transferred to the test apparatus.

Temperature of test liquid increased slowly temperature at which the vapours ignite is taken a flash point. Results are of limited value because the flash point obtained is usually the flash point of the most flammable component. which in case of topical hydrocarbons propellant.

MEASUREMENT VAPOR PRESSURE

Determined by pressure gauge

Pressure variation from container to container be determined, since excessive variation in pressure indicates the presence of air in headspace.

MEASUREMENT OF DENSITY

MOISTURE CONTENT
Method used Karl Fischer method G. C has also been used

IDENTIFICATION OF PROPELLANTS
1. G.C 2. I.R spectrophotometry

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 , the change in weight per time dispensed is discharge rate. It is expressed as gram per seconds.

Spray pattern
Spray the product on the coated (dye +talc ) Paper. Depending upon the nature of aerosol, water /oil soluble dye is used. The particles that strike the paper cause the dye to go into solution and to be absorbed on to the paper. This gives a record of spray.

Valve

Particle size( cascade impactor)

AEROSOL

Impaction slide

BIBLIOGRAPHY
Pharmaceutical aerosol formulation Url: www.google.com/patents/US7090831.pdf Accessed on 08/05/2012, 7.30 p.m. Url: http://www.china-pharmaceuticalmachine.com/product/47-semi-auto-aerosolpropellant-filler-pqgbi-14c9/ Accessed on 08/05/2012, 7.31p.m. Url: http://www.aerosolindia.in/aerosol machines.html Accessed on 09/05/2012, 5.30 p.m. Url:http://www.pharmacopeia.cn/v29240/usp29nf24 s0_c1151s8.html Accessed on 08/05/2012, 5.33 p.m.