Selection of Containers & Formulation Aspects of AEROSOLS Formulation

Guide : K.Rajitha By - Mohammed Zeeshan Saleem M.pharmacy Dept. of PHARMACEUTICS ( Hltkt.no : 12FP1S0323 )

Contents :

1. Definition

2. Classification

3. Components of aerosol system 4. Containers 5. Formulation

6. Quality control & Evaluation.

Definition :

• An Pharmaceutical aerosol is defined as

“pressurized containers, in which solid particles or liquid droplets constitute the disperse phase and gas in the continuous phase”.

• System that depends on the power of compressed or liquefied gas to expel the content from container.

Classification :1) Based on form : Solution, Suspension, Emulsion

2) Based on phases : Two phase - vapour + liquid Three phase - vapour + aq

(water)+ propellant

3) Based on product delivered : Spray (particle size 50microns in diameter), Foam, &

Semi solid (200microns in diameter.)

4) Based on application : Topical, Inhalation, Intranasal

Components of aerosol packagePropellants

Container

Valve Actuator

propellants :

These are compressed gases at 70 to 80 p.s.i.g They expel the contents of the container through valves by

applying force. They help in maintaining proper pressure in the container & are

they are considered as important elements in the formulation. Propellants used may be in the form of –

Liquefied gases &

Compressed gases

Liquefied Gases : • They are widely used in the formulation of aerosols

because they are capable of dispensing active ingredients in the form of fine mist.

• Liquefied propellants are actually gases which exists as liquid under pressure.

• Whenever the product is dispensed from the container, a part of liquid occupies the head space.

In this way the head space is always occupied by gas which maintains the constant pressure and performance of spray is also maintained.

Liquefied gases are of 3 types:

a) Chlorofluorocarbons. b) Hydro fluorocarbons. c) Hydrocarbons.

a)Chlorofluorocarbons : 3 types –

i) Trichloromonofluoromethane (propellant 11)

ii) Dichlorodifluoromethane. iii) Dichorotetrafluroethane.

b) Hydroflurocarbons : • Due to several dis-advantages with CFCs, they

have been replaced by Hydro fluorocarbons (HFCs)

• Several propellants like Tetrafluoroethane ( 134a ) & Heptafluoropropane ( 227 ) have been developed which are the substitutes of propellant 12

• These propellants have same properties as that of propellant 12, except solubility characteristics.

c) Hydrocarbons : They are used to formulate Topical aerosols, due to

following reasons –

• They donot undergo hydrolysis, & hence they are used in formulation of water based aerosols.

• As they are immiscible with water they are used in formulation of 3 phase aerosol system.

• They are used in MDIs & topical administration.

• They have wide range of solubility, chemically stable & low order of toxicity.

Physical properties :• Propellants (such as 11, 12, 114) are non-polar

compounds.• They are miscible with non-polar solvents at desired

temp & have ability to dissolve many substances.• They are immiscible with water, and hence to make

miscible with water, co-solvents such as ethanol can be added.

Chemical properties :• They are Chemically inhert, non-inflammable, non-

toxic• Propellant 11 undergoes hydrolysis, giving HCL,

hence it is not preferred in the formulation of Aq.aerosol product.

Compressed gases : These are of 2 types : a) Soluble C.gases ( CO2, N2O ) b) Insoluble gases ( Air, Nitrogen, Argon )• Propellants like O2 & CO2 are used as compressed

gases & helps in dispensing the product in the form of mist, foam or semi solid• In the c.gas spray system, the liquid product is poured

is poured into container & is sealed• The c.gas propellant is then filled under high pressure

into the container through the valve.• Due to the high pressure, the liq.product is forcefully

pushed down by the gas propellant.

• The C.gas propellant occupies only the head space,Present above the liq.product in the container

• When the valve of aerosol can is opened the liq.product,is pushed out through the nozzle.

• After the expulsion of the liq.product the amount of gas in the head space of the can still remains same, occupies more space thus reducing the pressure in the container.• The container is not completely filled with

liq.product, so as to provide enough head space for the gas propellant, thereby avoiding any possible risk of bursting of container.

Filling Machines :

CONTAINERS :

• Various types of materials are used in the manufacture of aerosol containers.

• The containers used in the formulation of aerosols should with stand high pressure i.e.,140 to 180 psig and temperature of about 54.44 c.

Types of materials used :

1. Metal

2. Glass

1)Metal : Two types of metal containers are used -

a) Tin plated steel &

b) Aluminum

2) Glass : Two types of glass containers are used - a) Plastic coated glass &

b) Uncoated glass.

Valves and Actuators :• The modern day aerosol valves are multifunctional i.e.

basic part of Aerosol containers as they deliver product in desired form, from the container & help’s in preventing the loss of product when the container is not in use.

Components of Continuous spray valves -

a) Mounting cup

b) Valve body

c) Stem

d) Gasket

e) Spring

F ) Dip tube

Metered valve aerosols :

Some metering type of valves have been designed which permit only a specified amount of product to come out .

Such valves actually consist of two valve's chambers both of which are connected to actuator.

Valve contain extremely small opening ( 0.018 to 0.030 inch )

Formulation of Aerosol’s :• Formulation of Aerosols involves two components

namely – a) Product concentrate b) PropellantsVarious type of systems are –1) Solution system / Two phase system2) Water based system / Three phase system3) Suspension / Dispersion system4) Foam system - a) Aq. Stable foams b) Non-aq.stable foams c) Quick breaking foams

1) Solution system :

Propellant 12 is used generally in formulation of this system, because it helps in producing very fine particles.

As A. ingredients are dissolved in propellants, solvents are not required.

The amount of propellant used in the system ranges from 5% (used in production of foams) to 95% (used in production of inhalation products)

2) Water based system : • Water is used to replace non-aq.solvents & ethanol

is used as a co-solvent to solubilize the propellant in water & also helps in producing small particles.

• This system also utilizes Surfactants (0.5 – 2.0%) to large extents, which helps in formation of homogenous dispersion.

Ex : Oleic, Stearic, Palmitic & Lauric acids

3) Suspension / Dispersion system :

• It consists of A. ingredients dispersed in propellant & this system is used for oral inhalation purposes.

• Surfactants / suspending agents are also utilized to decrease the rate of settling of dispersed a.ingredients.

• After the formation of suspension system, some particles show a tendency to aggregate due to solubility, moisture or particle size growth.

• When large agglomerates are formed then it leads to caking, & at higher temp. there is an increase in the rate of Agglomeration, which leads to flocculation.

• These particles stick to the wall of the container, leading to valve clogging resulting improper dosage & the particles also damage the metal container.

• Agglomeration is avoided by controlling the moisture content & in order to reduce agglomeration, surfactants & lubricants are also added.

Example of lubricants : Isopropyl myristate & Mineral oil.

4) Foam systems :

• This system consists of A.ingredient, aq & non-aq vehicle, surfactant & propellant.• These systems are dispensed in the form of

quick-breaking foams or stable foams.• This type of system is preferred for those

ingredients, which cause irritation as well as when aerosol is to be applied into limited area.

Various type of foam systems are : a) Aq.stable foams ; b) Non aq.stable foams c) Quick breaking foams ; d) Thermal foams

Quality Control :

QUALITY CONTROL TESTS Includes - 1. Containers. 2. Propellants. 3. Valves, Actuator, Dip Tubes. 4. Weight Checking. 5. Leak Testing. 6. Spray Testing.

Tests for Valves, Actuators & Dip tubes :

25 valves are selected which are placed on suitable containers, containing Test sol. (i.e., Test sol. 1, 2, 3)

To this container a button type actuator (0.020 inch of orifice) is attached.

The product in the container is allowed to attain a temp. of 24-26 degree centigrade, & weight is checked.

A single delivery is completely dispensed by pushing the valve at least for 2sec & the procedure is repeated for 10times & after dispensing a single delivery, the container is weighed.

Evaluation Tests :

A. Flammability & Combustibility :

1. Flash point 2. Flash Projection

B. Physicochemical Characteristics :

1. Moisture content 2. Identification of Propellants

C. Biological testing : 1. Therapeutic activity 2. Toxicity studies

Advantages :

A dose can be removed with out contamination of materials.

Stability is enhanced for those substances adversely affected by oxygen and or moisture.

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.

Ease of convenience of application.

Conclusion :

Aerosols are capable of dispensing the product in various forms, by which max. Therapeutic action can be achieved.

MDIs are capable of delivering the req.amount of drug to deep of the lungs.

With the help of Metered valve aerosols, specified amount of product can be dispensed.

With the help of Special type Actuators we can deliver the drug to specified sites.

References :

The Theory & Practice Of Industrial Pharmacy” by Leon Lachman, H.A.Liberman, Joseph Kanig, 3 rd Edition, Varghese Pub., page no. 613-618.

Remington’s “The Science & Practice Of Pharmacy” 3 rd Edition, Volume-I, page no.1014-1015.

 

Thank-u