2. Pulmonary drug delivery is a developing technology in which medication is
inhaled through the lungs and enters the bloodstream through the alveolar
epithelium. Pulmonary drug delivery provides a non-invasive, alternative method to
subcutaneous injection, and also intravenous injection.
Pulmonary route have been used to treat various respiratory
diseases for centuries. Ancient inhalation therapies included the use
of leaves from plants, vapors from aromatic plants, balsams, and
myhrr.
3. Pulmonary route possesses many advantages over other routes of
administration for the treatment of specific disease states,
particularly lung associated large protein molecules which degrade
in the gastrointestinal conditions and are eliminated by the first pass
metabolism in the liver can be delivered via the pulmonary route if
deposited in the respiratory zone of the lungs.
Devices used to deliver drug by pulmonary route area based on one of three
platforms pressurized metered dose inhaler, nebulizer and dry
powder .
4. • Contain a safe and efficacious drug.
• Contain minimal quantities of inert excipients
• Low velocity after generation.
• Highly concentration and rate of generation.
• Monodisperse , small particle size.
• Highly reproducible characteristics.
Ideal characteristics of Pulmonary Drug Delivery System
5. Aerosol is defined as a suspension system of solid or liquid
particles in a gas. An aerosol includes both the particles and
the suspending gas, which is usually air.
Aerosols are meant for topical, systemic , and oral
administration, these are also known as pressurized
packages.
The power propellants helps in expelling the contents from
the container.
6. ADVANTAGES OF AEROSOLS:-
1) Avoid first pass metabolism.
2) Deliver uniform dosage form.
3) Targeted drug delivery system.
4) Due to presence of propellant its produce cooling effect in site of action.
5) It is used for medicament that are sensitive for oxygen, moisture, light or heat
sensitive drug.
6) It is easy to use.
7. DISADVANTAGES OF AEROSOLS:-
1) It is difficult to prepare aerosols dosage form of insoluble drug.
2) If long term used of propellant it is produced toxic effect.
3) It is expensive dosage form.
4) Some time it contaminate drugs by its trace metal that presence in container.
5) Allergic in some cases.
6) Explosive.
8. .
TYPES OF AEROSOLS:-
a) Space Spray – This types of aerosols producing dispersion of particles which
remain in the air for prolonged periods. The particles of spray are usually less then
50 µm in size.
b) Surface coating spray - Such aerosols used for producing a film on the surface
treated this type of aerosols is relatively coarse. The particles range in size from
50 to 200 µm.
c) Foams- They are formed when expansion of propellant within an emulsion results
in production of small bubbles.
10. .
• It is responsible for developing proper pressure inside the container.
• When the valve is open they are release proper medicament
• It is regarded as the heart of aerosol package.
• .
12. .
A. Liquefied gas propellant :-
These are exits as liquids under pressure but when valve is opened they convert into gas. It
is divided into two sub types-
1)Chlorofluorohydrocarbon - It is mainly used for oral and inhalation preparation.
Examples are trichloromonofluoromethane (Propellant 11), dichlorodifluoromethane
(propellant 12) , dichlorotetrafluoromethane (propellant 114).
Advantages-
1.Chemical inertness. 3.Non flammibility.
2.Lack of explosiveness.
13. .
Disdvantages-
1.High cost..
2.It depletes the ozone layer.
2)Hydrocarbons - It can be used for water aerosols and topical use. Example propane
(propellant A-108), Butane(propellant A-17).
Advantages-
1. Inexpensive.
2. Excellent solvent.
14. .
Disadvantages-
1. Inflammable.
2. Unknown toxicity may be produced.
B. COMPRESSED GAS :-
Propellants can occupy the head space above the liquid. Example is carbon dioxide,
nitrous oxide and nitrogen.
When two propellants are mixture is vapor pressure is determined by Daltons law.
When propellants and other components are mix together its vapor pressure is
determined by Raoult’s law.
15. .
• Aerosol container are generally made up of glass, metal, and plastic.
• Aerosols container withstand with high pressure as high as 140-180 psig at 130 F.
• It is classified into three types -
16. .
Glass Container:- This type of container are used when low pressure and low amount
of propellant are used. In this type of container no corrosion problem are seen. This
type of container are used in Topical & MDIs aerosols.
It is also sub divided into two types-
Plastic container :- It is highly permeable to vapor so may be chance of oxidative
degradation in formulation.
17. .
Metal container :-This type of container are subdivided into three types-
1) Tin plated steel :-
• Tin are coated by electrolytic process.
• Three pieces of sheet.
• Joined by soldering.
18. .
• Use of vinyl or epoxy coating to prevent of reaction due to soldering.
• Use for topical aerosols.
Stainless steel –
• No coating required.
• Vinyl resins are not used in inside coating because of heat sterilized so epoxy is
widely used.
• Highly inactive.
• It is used for mainly inhalation aerosols.
• It is very costly it is only its dis advantage.
19. .
Aluminium-
• It is very light weight.
• The combination of Ethanol and propellant 11 in an aluminium container produces
hydrogen, acetyl chloride , aluminium chloride, propellant 21 and other corrosive
products.
• It is used both types of Aerosols MDIs & Topical aerosols.
20. .
Glass containers-
• These containers are preferred because of its Aesthetic value and absence of
incompatibilitIes.
• These containers are limited to the products having a lower pressure (33psig) and lower
% of the propellant.
• Used for topical and MDI Aerosols.
TYPES-
21. .
• 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-
22. .
• Dispersing of potent medication at proper dispersion/spray approximately 50 to
150mg + 10% of liquid materials at one time use of same valve.
VALVE COMPONENTS:-
23. .
These are specially designed buttons which helps in delivering the drug in desired form
i.e., spray , wet stream , foam or solid stream.
TYPES-
24. .
Spray actuators:-
It can be used for topical preparation, such as antiseptics, local anesthetics and spray on
bandages etc.
It allows the stream of product concentrate and propellant to pass through various
openings and dispense as spray.
Foam actuators:-
It consist of large orifice which ranges from 0.070-0.125 inch.
Solid stream actuators:-
These actuators are required for dispensing semi-solid products such as ointments.
25. .
Special actuators:-
These are used for a specific purpose.
it delivers the medicament to the appropriate site of action such as throat , nose ,
dental and eyes ,etc.
27. PRESSURE FILLING APPARATUS:-
It consists of a pressure burette capable of metering small volumes of liquified 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.
28. PRESSURE FILLING APPARATUS:-
The propellant stops flowing when the pressure of burette and container becomes
equal.
It 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 us of piston arrangement and is capable of
maintaining positive pressure.
29. COLD FILLING APPARATUS:-
It consist of an insulated box fitted with copper through and the tubing are coiled to
increase the area exposed to cooling.
The insulated box should be fitted with dry ice or acetone prior to use.
The apparatus can be operated with or without metered valves.
Hydrocarbon propellant can not be fitted into aerosol containers using this
apparatus because large amount of propellant escapes put and vaporizes.
This may lead to formation of an explosive mixture.
FC vapors do not form any explosive or flammable mixtures.
30. COMPRESSED GAS FILLING APPARATUS:-
CG have high pressure reducing valve is required.
The apparatus consists of delivery gauge.
A flow indicator is also present is specialized equipments.
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.
31. CONTAINERS:
i. Containers are examined for defects in lining.
ii. Quality control aspects includes degree of conductivity of electric current
as measure of exposed metals.
iii. Glass containers examined for flaws.
WEIGHT CHECKING:
i. It is done by periodically adding to the filling line tared empty aerosol
containers, which after filling with concentrate are removed & weighed.
ii. Same procedure is used for checking weight of propellants being added.
32. LEAK TESTING:
i. It is a means of checking crimping of the valve and detect the defective
containers due to leakage.
ii. It is done by measuring the crimp’s dimension & comparing.
iii. Final testing of valve closure is done by passing the filled containers
through water bath.
SPRAY TESTING:
i. Most pharmaceutical aerosols are 100% spray tested.
ii. This serves to clear the dip tube or pure propellant and pure concentrate.
33. III. To check for defects in valves and spray pattern.
FLASH POINT:
Apparatus - Tag Open Cup Apparatus
Product is chilled to – 25 F and test liquid temperature is allowed to increase
slowly and the temperature at which vapors ignite is called as “Flash Point”
34. FLAME PROJECTION:
Product is sprayed for 4 sec into a flame and the flame is extended, exact length
is measured with a ruler.
VAPOR PRESSURE:
Pressure Gauge
Can puncturing device.
DENSITY:
Hydrometer.
pycnometer.
35. MOISTURE:
Karl fisher method
Gas chromatography.
IDENTIFIVCATION OF PROPELLANTS:
Gas chromatography
IR spectroscopy.
NET CONTENTS:
Tared cans that have been placed into the filling lines are reweighed and the difference in
weight is equal to the net contents.
In destructive method, weighing a full container & then dispersing as much as possible.
The contents are then weighed which gives net content.
