pharma aerosols

PHARMACEUTICAL AEROSOLS: 

PHARMACEUTICAL AEROSOLS Presented By : Mr. Naresh Rajgor, Assistant Professor, M.P. Patel College of Pharmacy, Kapadwanj

PHARMACEUTICAL AEROSOLs : 

PHARMACEUTICAL AEROSOLs

DEFINITION “Aerosol is pressurized dosage form in which therapeutically active drug is dissolved or dispersed or suspended in compressed or liquefied gas to expel the content from the container in the form of spray.” OR “A system that depends on the power of compressed or liquefied gas to expel the contents from the container.” : 

DEFINITION “ Aerosol is pressurized dosage form in which therapeutically active drug is dissolved or dispersed or suspended in compressed or liquefied gas to expel the content from the container in the form of spray.” OR “A system that depends on the power of compressed or liquefied gas to expel the contents from the container.”

PowerPoint Presentation: 

Aerosol mainly used for the treatment of Asthma and COPD disease etc…. Aerosols are used for either topical , oral or nasal administration in the form fine particles or mist or fog. In mid 1950 the pharmaceutical aerosol introduced in market.

ss: 

ss

Components of aerosols: 

Components of aerosols Aerosol consist of 1. Product concentrate 2. Propellant 3. Container 4. Valve and actuator

1. PRODUCT CONCENTRATE: 

1. PRODUCT CONCENTRATE It consist of API, Additives like suspending agent, emulsifying agent , antioxidant, aqueous and non aqueous, co-solvent etc…

2. PROPELLANT : 

2. PROPELLANT It is responsible for developing the vapour pressure with in the container and also expel the product when the valve is opened and in the atomization or foam production of the product. It is classified in to mainly three types 1. Liquified gas system a) Flourinated hydrocarbon(FHC) b) Chloro fluro carbon (CFC) C) Hydrocarbons (HC) 2. Compressed gas system 3.Hydrofluoroalkanes

1. LIQUIFIED GAS SYSTEM : 

1. LIQUIFIED GAS SYSTEM These compounds are gases at room temperature and atmospheric pressure .However they can be liquefied easily by lowering the temperature (below the boiling point or by increasing pressure ). These compounds are chosen generally have B.Pt below 700F and vapour pressure between 14 and 85 psia at 700 F When it is placed into sealed container it immediately separates into a liquid and a vapour phase. Some o f the propellant molecule will leave from the liquid state to vapor state. The pressure at this point is called vapour pressure It is denoted by the symbol Psia (pounds per square inch absolute) As molecule enter the vapor state a pressure gradually develops no .of molecule in vapour state = vapor pressure

PowerPoint Presentation: 

PHYSIOCHEMICAL PROPERTIES OF PROPELLANTS are Vapor pressure Boiling points Liquid density

PowerPoint Presentation: 

Vapor pressure of mixture of propellants is calculated by Doltan’s law which states that total Pressure in any system is equal to the sum of individual or partial pressure of various compounds. Raoult’s low regards lowering of the vapor pressure of a liquid by the addition of another substance, states that the dispersion of the vapor pressure of solvent upon the addition of solute is proportion to the mole fraction of solute molecules in solution. The relationship can be shown mathematically

3. CONTAINER: 

3. CONTAINER

1. Tin plate containers: 

1. Tin plate containers It consist of a sheet of steel plate that has been electroplated on both sides with tin. The size of the container is indicated by a standard system and measured by height and weight. 2. Aluminum containers greater resistance to corrosion Light weight, not fragile Good for light sensitive drugs

PowerPoint Presentation: 

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.

4. Actuator and valve: 

4. Actuator and valve

PowerPoint Presentation: 

2. Stem: it is made of nylon /delrin/s.steel It contains one or more orifice (0.013 to 0.030) 3. Gasket : It is made of Neoprene rubber 4. Spring: It is used to hold the gasket in a place and when actuator is depressed it returns the valve in closed position It is made of stainless steel 5. Dip tube : It is made up of poly propylene material / poly ethylene Inside diameter (0.120 – 0.125) for tube and viscous product is 0.195

B. Metering Valve: 

B. Metering Valve Metering valves are applicable to the dispensing of potent medication. These operate on the principle of a chamber whose size determines the amount of medication dispensed. Approximately, 50 to 150 mg of liquid material can be dispensed at one time with use of such valves.

FORMULATION OF PHARMACEUTICAL AEROSOL: 

FORMULATION OF PHARMACEUTICAL AEROSOL

1. SOLUTION SYSTEM : 

1. SOLUTION SYSTEM This system referred to as a two phase system and consists of two phases: a vapor phase and a liquid phase. When the active ingredients are soluble in the propellant, no other solvent is required. Depending on the type of spray required, the propellants are used. Propellant 12 produce fine particle, but when the other type of propellant is added with this one, it reduces the vapour pressure and produce large particles.

PowerPoint Presentation: 

The amount of propellant used may vary from 5% to 95%. This system can be best explained by the following general formulations. Weight (%) Active ingredients to 10-15 Propellant 12/11 (50:50) to 100 Solution aerosols produce a fine to coarse spray, depending on the concentration of the other ingredients. Hydrocarbon propellants A-70 produces a drier particles, while A-17 and A-31 tend to produce a wetty spray.

2. WATER BASED SYSTEM: 

2. WATER BASED SYSTEM It is three phase system containing vapour phase, propellant , water. Some non- aqueous solvents replace with water so called as a water based system so called as a spray or foam system. Ethanol used as a co-solvent to solubilize the propellant in water. Surfactants (0.5-2%) have been used to a large extent to produce a satisfactory homogeneous dispersion. Propellant content varies from 25 -60%.

PowerPoint Presentation: 

A recent development that is useful for pharmaceutical aerosols is the Aquasol valve. This new Aquasol system allows for the dispensing of a fine mist or spray of active ingredient and dissolved water, which is not possible with three phase system. Since only water and active ingredient are dispensed.(propellant is in vapor phase and have a little quantity.) Depending on the configuration of the valve and actuator, either a fine dry spray or a coarse wet spray can be obtained.

3. SUSPENSION SYSTEM: 

3. SUSPENSION SYSTEM Various methods have been used to overcome the difficulties encountered that are due to the use of co-solvent. It is prepared by dispersion active ingredients in mixture propellant and by using suspending agent. The system have been developed primarily for the use with oral inhalation aerosols. Ex: Weight (%) Epinephrine bitartrate 0.50 Sorbitan trioleate 0.50 Propellant 114 49.50 Propellant 12 49.50

PowerPoint Presentation: 

The epinephrine bitartrate has a minimum solubility in the propellant system, but is sufficiently soluble in the fluids in the lungs to exert a therapeutic activity. The physical stability of an aerosol dispersion can be increased by control of moisture content. Use of derivatives of active ingredient having minimum solubility in propellant. Reduction of initial particle size to less than 5 micron. Use of dispersing agents. In this system, there are chances of agglomeration. Various agents like isopropyl myristate and mineral oils are used to reduce agglomeration.

4. FOAM SYSTEM: 

4. FOAM SYSTEM They contain Dispersion of API, Vehicle, surfactant and propellant. Liquefied propellant used as internal phase. a. Aqueous stable foam : Ingredients( antiseptic ) oil waxes O/W surfactant Water Hydrocarbon propellant

PowerPoint Presentation: 

b. Non aqueous stable foam Non-aqueous stable foams may be formulated through the use of glycols (PEG). Emulsifying agent used this type PEG Esters (PEG monostearate). Ingredients Glycol 91-92.5 % Emulsifying agent 4 % Hydrocarbon propellant 3.5-5.0 %.

c. Quick breaking foam: 

c. Quick breaking foam In this system, the propellant is in the external phase. When dispensed, the product is emitted as a foam, which then collapses into a liquid. This type of system is especially applicable to topical medication, which can be applied to limited or to large areas without the use of mechanical force to dispense the active ingredients. Ex: Ethyl alcohol 46-66 % Surfactant 0.5-5 % Water 28-42% Hydrocarbon propellant 3-15%

d. Thermal Foams: 

d. Thermal Foams These foams were developed several years ago and were used to produce a warm foam for shaving. They were not readily accepted by costumer. The same technology were used for hair color and dyes, but unfortunately they were subject to some problem.

5. INTRANASAL AEROSOLS: 

5. INTRANASAL AEROSOLS Drug delivery through intra nasal has long been used as most effective way for administration of drugs. Until recently, the modes of administering intranasal preparations have been limited to nasal drops, non pressurized nasal sprays, inhalants, intra nasal gels, creams and ointments. A new alternative to this preparation is the pressurized meter nasal aerosols.

PowerPoint Presentation: 

The advantages through the intranasal ways are measured dose of drug, depth of penetration into the nasal passageway, reduce droplet size, lower dose than other route etc. Ex: Active ingredient 1.0 % Dispensing agents, additives 1.0 % Propellant (12/11) 98%

Name of the available products.: 

Name of the available products. Sr. No Trade Name Dosage Form Active Ingredient Indication 1 Decadron Turbinaire Pressurized aerosol suspension Dexamethasone sodium phosphate Allergic or inflammatory nasal condition 2. Beconase or Vancenese Pressurized aerosol suspension Beclomethasone dipropionate Seasonal and perennial rhinitis.

TYPES OF AEROSOLS DELIVERY: 

TYPES OF AEROSOLS DELIVERY Nebulizers Used to administer medication to people in the form of a mist inhaled into the lungs. Meter dose Inhaler (MDI) It pressurized, hand-held devices that use propellants to deliver doses of medication to the lungs of a patient Propellant driven aqueous pump sprays Dry powder inhaler (DPI) Delivers medication to the lungs in the form of a dry powder.

PowerPoint Presentation: 

It is a device used to converting a liquid drug (Solution /suspension) into a fine mist which can then be inhaled easily Two types: • Jet Nebuliser( air jet /air blast) • Ultrasonic Nebuliser

PowerPoint Presentation: 

It is powered by high pressure air Nebulizer commonly used in hospital and home for drug administration have small medication reservoirs(<10ml)

METERED DOSE INHALER : 

METERED DOSE INHALER Metered-dose inhalers (MDIs), introduced in the mid 1950. In MDIs, drug is either dissolved or suspended in a liquid propellant mixture together with other excipients, including surfactants and presented in a pressurized canister fitted with a metering valve . A Predetermined dose is release when up on actuation.

PowerPoint Presentation: 

When released from the canister the formulation undergoes volume expansion in the passage within the valve and forms mixture of gas. The high speed of gas flow break the liquid into fine droplets MDI are Generally Packed In aluminum steel canister with a capacity of 20 -30 ml. Aluminium is inert material . So either coated with epoxy material. CFC used as a propellant in MDI Preparation along with surfactant and lubricant. eg. CFC -11, CFC -12, CFC-14 Alternative for propellant CFC – HFA-134,127

DRY POWDER INHALER(DPI): 

DRY POWDER INHALER(DPI) In DPI the drug is inhaled as a cloud of fine particle . The drug is either preloaded in the inhaled device or filled in hard gelatin capsule . DPI are propellant free. No additive except carrier like lactose . It can deliver large dose than MDI

MANUFACTURING OF PHARMACEUTICAL AEROSOL: 

MANUFACTURING OF PHARMACEUTICAL AEROSOL Apparatus COLD FILLING PROCESS PRESSURE FILLING PROCESS COMPRESSED GAS FILLING PROCESS

Preparation of product concentrate: 

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.

COLD FILLING APPARATUS: 

COLD FILLING APPARATUS

PowerPoint Presentation: 

The cold filling aerosol line consists of: 1.Un-scrambler 2.Air-cleaner 3.Concentrate filler (capable of being chilled) 4.Propellant filler 5.Valve placer 6.Vaccum purger 7.Valve crimper 8.Heated water-bath 9.Labeler 10.Coder and packaging table

PowerPoint Presentation: 

The principle of cold filling method requires the chilling of all components including concentrate and propellant to a temperature of 30 to -40 º F. This temperature is necessary to liquefy the propellant gas . The cooling system may be a mixture of dry ice and acetone or refrigeration system. First, the product concentrate is chilled and filled into already chilled container followed by the chilled liquefied propellant. The heavy vapour of the cold liquid propellant generally displace the air in the container

PowerPoint Presentation: 

Single head or multiple head rotary unit capable of vacuum crimping up to 120 can / min are available. The rotary unit requires air pressure (90 to 120 lbs / inch) and vacuum. A valve is placed either manually or automatically depending on the production rate required. The valve is crimped in place by using valve crimper. Advantages Easy process Disadvantages Chilling of the product, container and propellant is required. Aqueous products, emulsions and those products adversely affected by cold temperature cannot be filled by this method.

TESTING OF FILLED CONTAINER : 

TESTING OF FILLED CONTAINER The container passes through a heated water bath in which the contents of the container are heated to 130ºF to test for leaks and strength of the container. The container is air dried, spray – tested, capped and labeled.