SAMARTH PHARMA
Aerosols consists of the gas that may be compressed or liquefied and it has capability to bring out the drug and other ingredients out of the container.(1)
Why aerosols...??
Aerosols have a number of advantages,which includes:(1)
1.Product can be maintained free of contamination. Substances that get spoiled by oxygen or moisture can be maintained.
2. Wherever the medicament is needed,there the product can be delivered in the required form like foam,spray etc…
3. If the drug is applied topically,it causes irritation. This can be avoided with the use of aerosols.
Components:-(1)
The components of the aerosols include
1. Propellant
2. Container
3. Valve and actuator
4. Product concentrate.
Formulation:-(1)
It essentially consists of two main components,
1. Product concentrate
2. Propellant
Product concentrate includes drug,surfactants,solvents,anti-oxidants,etc.
Propellant includes one propellant or a mixture of propellants. Mixture of propellants are used to get the desired vapour pressure.
Based on the type,different forms of pharmaceutical aerosol can be delivered.
Types of system:(1)
Solution system:
It consists of the vapour and the liquid. It is also called two-phase system. No other solvent is required if the drug is soluble in the propellant. Based on the type of spray required, either propellant 12 is added or other propellants are also added. When less volatile substances are added to the system,three phase system is produced based on the amount of water present. Dried particle is obtained on the use of A-70 and wetten particles on use of A-17 and A-31.
Water based system:
If only water or large amount of water is present to solubilize the contents then it is called water based system. If spray form is required, then active ingredient is dispersed and other solvents should be present in the form of emulsion and propellant will be external phase. As the water is not miscible in propellant,generally three phase system results. To increase the solubility of propellants in water,ethyl alcohol can be added to the system.
To produce a uniform dispersion,surfactants can be used and those surfactants which are soluble to large extent in non polar solvents and soluble to smaller extent in water are more preferred. Ester formed between glycol ,glycerol and polyhydroxylic acid like oleic,palmitic stearic acids can be used as surfactants. The surfactants composition ranges between 0.5 to 2.0 and propellant composition ranges from 25 to 60%
The recent advancement is the aquasol valve . in aquasol dispenser system, the drug is dissolved in the water or the mixture of water and alcohol. Then the propellant layer is present on the top water layer. The solubility of the propellant increases as the amount of alcohol increases and will become completely soluble if only alcohol is present.
In aquasol,the vapourized propellant and product via different ducts reaches the actuator. Here the randomization takes place which gives an uniform spray.
Fig 1 aquasol (2)
Water based systems produces the dried spray.
Suspension or dispersion systems:
There comes a number of problems by the use of cosolvent. To overcome this,suspension system is developed. In this system,in the propellant or the blend of propellants,the drug particles are suspended. Surfactants are added to reduce the settling rate.
To increase the physical stability
1. Moisture content must be monitored
2. The particles should have less solubility.
3. Add suspending agents.
4. By decreasing the density difference.
5. The particle size should be maintained less than 5microns.
Agglomerates will be formed in case of certain substances, if the number of agglomerates increases then caking results. As the temperature increases this condition will be increase. At extreme conditions, the particles will get attached to the walls. More the moisture content, more will be the agglomeration.
Foam system: Here the propellant which is present in the liquid acts as internal phase.here the ingredients include aqueous or nonaqueous vehicle, propellant and surfactant.
Aqueous stable foams: This consists of propellant in the range of 8 to 10% v/v. As the concentration of A-70, A-46 propellant increases, it results in drier spray. And wetter spray is produced as the concentration of propellant decreases. This is generally used for steroid antibiotics.
Nonaqueous stable foams: Glycols are used in the formulation of these foams and their esters are used as emulsifying agents.
Quick breaking foams: here the external phase is propellant. The product will come out as foam which soon merges to form liquid. This type of system can be applied to small area or larger surface. Cationic or anionic or non-ionic surfactants are used in the formulation.
Thermal foams are not used much these days. These are used when the warmness is required.
Intranasal aerosols:
The design of the adaptor varies from the inhlationaerosols. The adaptors will be of less height and narrow, which results in the production of less number of smaller particles.
It has number of advantages like contamination free, very less quantity of drug moves into the lungs, the mucosal irritation will be reduced.
Propellants: (1)
HFC's though ideal cannot be used because of the environmental pollution.
e.g. propellant 12, propellant 114 etc.
There are some other choices like fluorocarbons , hydrocarbons and compressed gases.
The containers are generally made up of glass or metal. But brittleness restricts the use of glass. If the pressure is less than 25psig and propellant content is less than 15% then glass can be used. Glass should be coated with plastic coating in two layers if pressure is less than or equal to 33psig.
Epoxy and vinyl resins can be used as linings. Vinyl resins can form strong lining but it will get damaged by steam. But epoxy resins can be used as they are resistant to steam. A vinyl coating on which the epoxy coating is most suitable for products having less pH.
MANUFACTURING PROCEDURE:(1)
It includes two steps.
1. Concentrate preparation
2. Propellant is mixed
With help of the procedures that are previously accepted, the product is manufactured and then tested.
The filling of aerosols in to the containers can be done by two methods namely
1. Cold filling method
2. Pressure filling method
Cold filling method:
Aerosols consists of the gas that may be compressed or liquefied and it has capability to bring out the drug and other ingredients out of the container.(1)
Why aerosols...??
Aerosols have a number of advantages,which includes:(1)
1.Product can be maintained free of contamination. Substances that get spoiled by oxygen or moisture can be maintained.
2. Wherever the medicament is needed,there the product can be delivered in the required form like foam,spray etc…
3. If the drug is applied topically,it causes irritation. This can be avoided with the use of aerosols.
Components:-(1)
The components of the aerosols include
1. Propellant
2. Container
3. Valve and actuator
4. Product concentrate.
Formulation:-(1)
It essentially consists of two main components,
1. Product concentrate
2. Propellant
Product concentrate includes drug,surfactants,solvents,anti-oxidants,etc.
Propellant includes one propellant or a mixture of propellants. Mixture of propellants are used to get the desired vapour pressure.
Based on the type,different forms of pharmaceutical aerosol can be delivered.
Types of system:(1)
Solution system:
It consists of the vapour and the liquid. It is also called two-phase system. No other solvent is required if the drug is soluble in the propellant. Based on the type of spray required, either propellant 12 is added or other propellants are also added. When less volatile substances are added to the system,three phase system is produced based on the amount of water present. Dried particle is obtained on the use of A-70 and wetten particles on use of A-17 and A-31.
Water based system:
If only water or large amount of water is present to solubilize the contents then it is called water based system. If spray form is required, then active ingredient is dispersed and other solvents should be present in the form of emulsion and propellant will be external phase. As the water is not miscible in propellant,generally three phase system results. To increase the solubility of propellants in water,ethyl alcohol can be added to the system.
To produce a uniform dispersion,surfactants can be used and those surfactants which are soluble to large extent in non polar solvents and soluble to smaller extent in water are more preferred. Ester formed between glycol ,glycerol and polyhydroxylic acid like oleic,palmitic stearic acids can be used as surfactants. The surfactants composition ranges between 0.5 to 2.0 and propellant composition ranges from 25 to 60%
The recent advancement is the aquasol valve . in aquasol dispenser system, the drug is dissolved in the water or the mixture of water and alcohol. Then the propellant layer is present on the top water layer. The solubility of the propellant increases as the amount of alcohol increases and will become completely soluble if only alcohol is present.
In aquasol,the vapourized propellant and product via different ducts reaches the actuator. Here the randomization takes place which gives an uniform spray.
Fig 1 aquasol (2)
Water based systems produces the dried spray.
Suspension or dispersion systems:
There comes a number of problems by the use of cosolvent. To overcome this,suspension system is developed. In this system,in the propellant or the blend of propellants,the drug particles are suspended. Surfactants are added to reduce the settling rate.
To increase the physical stability
1. Moisture content must be monitored
2. The particles should have less solubility.
3. Add suspending agents.
4. By decreasing the density difference.
5. The particle size should be maintained less than 5microns.
Agglomerates will be formed in case of certain substances, if the number of agglomerates increases then caking results. As the temperature increases this condition will be increase. At extreme conditions, the particles will get attached to the walls. More the moisture content, more will be the agglomeration.
Foam system: Here the propellant which is present in the liquid acts as internal phase.here the ingredients include aqueous or nonaqueous vehicle, propellant and surfactant.
Aqueous stable foams: This consists of propellant in the range of 8 to 10% v/v. As the concentration of A-70, A-46 propellant increases, it results in drier spray. And wetter spray is produced as the concentration of propellant decreases. This is generally used for steroid antibiotics.
Nonaqueous stable foams: Glycols are used in the formulation of these foams and their esters are used as emulsifying agents.
Quick breaking foams: here the external phase is propellant. The product will come out as foam which soon merges to form liquid. This type of system can be applied to small area or larger surface. Cationic or anionic or non-ionic surfactants are used in the formulation.
Thermal foams are not used much these days. These are used when the warmness is required.
Intranasal aerosols:
The design of the adaptor varies from the inhlationaerosols. The adaptors will be of less height and narrow, which results in the production of less number of smaller particles.
It has number of advantages like contamination free, very less quantity of drug moves into the lungs, the mucosal irritation will be reduced.
Propellants: (1)
HFC's though ideal cannot be used because of the environmental pollution.
e.g. propellant 12, propellant 114 etc.
There are some other choices like fluorocarbons , hydrocarbons and compressed gases.
- Water based aerosols and foam systems utilize hydrocarbons.
- Compressed gases can be used for topical preparations as they do not cause chilling effect.
- Now hydrocarbon propellant can be used for aqueous and solvent based aerosols. In the formulation of all types of topical aerosols, hydrocarbons can be used.
- The use of nitrogen, carbondioxide is restricted.
The containers are generally made up of glass or metal. But brittleness restricts the use of glass. If the pressure is less than 25psig and propellant content is less than 15% then glass can be used. Glass should be coated with plastic coating in two layers if pressure is less than or equal to 33psig.
Epoxy and vinyl resins can be used as linings. Vinyl resins can form strong lining but it will get damaged by steam. But epoxy resins can be used as they are resistant to steam. A vinyl coating on which the epoxy coating is most suitable for products having less pH.
MANUFACTURING PROCEDURE:(1)
It includes two steps.
1. Concentrate preparation
2. Propellant is mixed
With help of the procedures that are previously accepted, the product is manufactured and then tested.
The filling of aerosols in to the containers can be done by two methods namely
1. Cold filling method
2. Pressure filling method
Cold filling method:
There is another choice for this method…
In another method both the propellant and the product I cooled
to -40 F in the pressurized container and mixed well. Then it will be added to
the container. Now heat the container to
130F to check the leaks.
to -40 F in the pressurized container and mixed well. Then it will be added to
the container. Now heat the container to
130F to check the leaks.
Coming to pressure filling, which is more prominent than
cold filling method as most of the formulations cannot be cooled to very low
temperatures
cold filling method as most of the formulations cannot be cooled to very low
temperatures
Pressure filling method is as follows
Reference
- The
theory and practice of Industrial Pharmacy by Leon Lachman, Herbert A. Liberman,
Joseph L. Kaing, and Joseph L. Kaing, Third edition, Varghese Publishing House,
page no 589 to 613 - http://books.google.co.in/booksid=agEAAAAAMBAJ&pg=PA54&lpg=PA54&dq=aquasol+valve+from+popular+science&source=bl&ots=hkK_5ID__W&sig=jRHVore-63lW2vhl_278ggOtPlc&hl=en&ei=AqITdnDJomHrAf7uJnHDg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBYQ6AEwAA#v =onepage&q&f=false( accessed on march 20 th 9:53pm)
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