PHARMACEUTICAL AEROSOL

K.Senthil kumar M.Pharm Asst.Prof QIS college of Pharmacy,Ongole .Andhra pradesh

INTRODUCTIONAerosol is pressurized dosage form in which therapeutically active drug is dissolved or dispersed or suspended in compressed or liquified gas to expel the content from the conatiner in the form of spray

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.

DRUGS USE IN AEROSOLS

ADVANTAGESIt produce Rapid action. It is suitable for when the degrade in GI tract. It Directly applied to the affected area. It Prevents to Oxidation of drugs It can avoid the hepatic metabolism of drugs. It can be maintain sterility& easy to portable It produce local & systemic effect( due to large surface area of lung and blood capillary )

DISADVANTAGESLimited safety hazard (Flammable Nature) It is a Costly Preparation It is a chance for continuous deposition of particle in upper respiratory tract The propellant may cause chillness to the skin

TYPES OF AEROSOL SPRAYThere are three types of aerosol spray. 1. Space sprays 2. Surface coating spray 3. Foam spray

SPACE SPRAYThese products are delivered as a fine mist is called space spray .It contains 85% propellant and it is pressurized at 700F with 30-40 psig. It contains not more than 50 m of particle. So it can be retain in air. eg. Room sprays

SURFACE & FOAM SPRAYAerosols intended for carrying active ingredients to surface are termed as surface sprays or surface coating spray. It contains 30 70% propellant operate between 2255 psig at 700F. Eg. Topical Aerosol Foam aerosols(emulsion ) usually operate between 35 and 55 psig at 21c and contains only 6-10% propellant.

PHYSIOLOGY OF RESPIRATORY TRACT

The main function of respiratory tract is transfer of O2 from inspired air to blood and removal of Co2 from the blood. Respiratory tract divided in to two parts 1.Upper respiratory tract { Nose ,throat , pharynx and larynx } 2. Lower respiratory tract {Trachea, bronchi, bronchioles ,and alveoli }

DIAGRAM OF HUMAN AIRWAYS

PARTICLE DEPOSITION IN RPTIf Particles size >100 m in diameter may deposit in the oropharyngeal cavity. If Particles between 10 to 60m will be deposited on the epithelium of the bronchial tract. If Particles Size is < 2 m in diameter can reach the alveoli.

AEROSOL CONTAINER

MECHANISM OF PARTICLE DEPOSITION IN RPTThere are four mechanisms to operate aerosols 1. Interfacial interception 2. Brownian diffusion 3. Gravitational sedimentation 4. Electrostatic precipitation

INERTIAL IMPACTIONInertial impaction occurs because a particle traveling in an air stream has its own momentum (the product of its mass and velocity) As the direction of the airflow changes due to a bend or obstacle, the particle will continue in its original direction for a certain distance because of its inertia. Impaction of particles entering the mouth with a high velocity occurs either at the back of the mouth or at the bend where the pharynx leads to the trachea. Only a small fraction of particles greater than 15 m will reach the trachea following mouth breathing.

CONTINDeposition by impaction will also occur as the trachea splits into the left and right bronchus.

GRAVITATIONAL SEDIMENTATION(GS)GS is the downward movement of particle under the action of gravity .

CONTIN.If particle size is less than 5m deposition in bronchioles and alveoli. Particles settle by gravitation onto the airway walls.

It was explained by stokes Law V= 2r2 (d1-d2)g 9

BROWNIAN DIFFUSIONCollison and bombardment of small particle by the molecule in the respiratory tract to produce Brownian motion.

CONTIN..Brownian motion or diffusion is a mechanism which significantly affects only particles less than 0.5 m in diameter

These particles are subjected to bombardment by surrounding gas molecules causing random movement of the particles. In this situation, the diffusivity of a particle is inversely proportional to its diameter.

INTERCEPTIONIf the particles contact the airway surface because of their larger dimension of particle

ELECTROSTATIC PRECIPITATIONThe charge on the surface of the particle may affect the resultant deposition i.e. Surface of charged particle( + ve ) interact with a site within the respiratory tract that posses on opposite charge (-ve). Unipolar charged aerosols with high number concentrations repel each other and drive particles towards the walls.

BREATHING PATTERNBreathing pattern ,lung physiology will affect the deposition of particle.

Breath holding after inhalation enhances the deposition of particle by sedimentation and diffusion.

COMPONENT OF AEROSOLAerosol consist of 1. Product concentrate 2. Propellant Product concentrate consist of API, Additives like suspending agent , emulsifying agent , antioxidant, aqeous and non aqueous ,cosolvent etc

PROPELLANTIt 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 two types 1. Liquified gas system a) Flourinated hydrocarbon(FHC) b) Chloro fluro carbon (CFC) C) Hydrocarbons (HC) 2. Compressed gas system 3.Hydrofluoroalkanes

LIQUIFIED GAS SYSTEMThese compounds are gases at room temperature and atmospheric pressure .However they can be liquified 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 separartes into a liquid and a vapour phase

CONTIN..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 As molecule enter the vapor state a pressure gradually develops no .of molecule in v.state = vapor pressure

FLUORINATED HYDROCARBONSIt is Used for oral and inhalation aerosol preparation. Chemical NameTrichloromonoflouromethane Dichlorodifluoromethane Dichlorotetrafluroethane Chloropentaflouroethane Monochlorodifluroethane Difluroethane Octaflurocyclobutane

Chemical FormulaCCl3F CCl2F2 CClF2CClF2 CClF2CF3 CH3CClF2 CH3CHF2 CF2CF2CF2CFM2 12

Numerical Designation11 12 114 115 142b 152 b C318

CONTINPsia means = pounds per square inch absolute The term psig ( pounds per square inch inch gauge) 0 Psig = 14.7 Psia Eg. Flourinated hydro carbon

CHLORO FLURO CARBON( CFC)AdvantagesLow inhalation toxicity High chemical stability High purity CFC-11 is a good solvent

DisadvantagesDestructive to atmospheric Ozone Contribute to greenhouse effect High cost

eg.

1.Hydrochlorocarbon 2.Hydroflurocarbon 3. Hydrochloro flurocarbon

HYDROCARBONSChemical NameButane Isobutane Propane

Numerical DesignationA-17 A-31 A-108

It is mainly used for for the preparation of topical preparation

CONTIN..Chemically stable No hydrolysis Inflammable Low toxicity They are lighter than water

COMPRESSED GAS SYSTEMAdvantagesLow inhalation toxicity High chemical stability High purity Inexpensive No environmental problems

DisadvantagesRequire use of a nonvolatile co-solvent Produce course droplet sprays Pressure falls during useEg.. Co2 , No,N2

HYDROFLUOROALKANESAdvantagesLow inhalation toxicity High chemical stability High purity Not ozone depleting

DisadvantagesPoor solvents Minor greenhouse effectHigh cost e.g. 1,1,1,2,3,3,3 Heptafluoropropane (HFA-227), 1,1,1,2 Tetrafluoroethane (HFA-134a)

PHYSIOCHEMICAL PROPERTIES OF PROPELLANTS

Vapor pressure Boiling points Liquid density

Vapor pressure of mixture of propellants is calculated by Doltans law which states that total Pressure in any system is equal to the sum of individual or partial pressure of various compounds

Raoults 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 : na pa = ------------ pAo =NApAo ----------(1) na + nb

AEROSOL CONTAINERThey must be stand at pressure as high as 140 to 180 psig (pounds per sq. inch gauge) at 1300 F. A. Metals 1. Tinplated steel (a) Side-seam (three pieces) (b) Two-piece or drawn (c) Tin free steel 2. Aluminium (a) Two-piece (b) One-piece (extruded or drawn) 3. Stainless steel B. Glass 1. Uncoated glass 2. Plastic coated glass

AEROSOL CONTAINERSContainers must withstand pressure as high as 140 to 180 psig 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 Light weight, not fragile Good for light sensitive drugs

Stainless steel containerLimited for smaller size Extremely strong and resistant to most materials Pressure stand

4. Glass containersAvailable 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 AEROSOLSActuator Ferrule or mount cap Valve body or housing Stem Gasket Spring Dip tube

TYPES OF ACTUATORActuators: 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 Foam Actuators Solid Stream Actuators Special Actuators

CONTIN..Spray actuatorThe stream of product concentrate and propellant are dispensed in the form of small particle through orifices 0.016- 0.040inch.

Large orifice are used when high pressure of propellant 12 Foam Actuator: They contain large orifice diameter 0.070-0.125 inch Semisolid stream actuator: It is used for dispensing semisolid dosage form Special actuator: They are specially designed to deliver the medicament on the specific sites like nose , throat

TYPES OF AEROSOL VALVES1.Continuous spray valveMounting Cup / Ferrule Valve body or Housing Stem valve Gasket Spring Dip Tube

2. Metering valve

VALVERegulate 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

continuous spray valve

FERRULE/ mounting cupIt is used to attach the valve in proper position in container.it is necessary coated with epoxy resin.

Valve body / housing : It is made of nylon/delrin and contains at the opening point of diptube(0.013 to 0.080 inch) It prevents clogging of p.size,reduce chilling effect of the skin

Stem:it is made of nylon /delrin/s.steel It contains one or more orifice (0.013 to 0.030) Gasket : It is made of Buna N, Neoprene rubber 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 Dip tube : It is made up of poly propylene material / poly ethylene Inside diameter (0.120 0.125) for c.tube ( 0.050 inch and Viscous product 0.195)

TYPES OF AEROSOL SYSTEMThere are five types of aerosol systemSolution system / Two phase system Water based system / Three phase system Suspension or Dispersion system Foam systemAqueous stable foam Non-Aqueous stable foam Quick Breaking Foam Thermal foam

Intranasal foam

SOLUTION SYSTEMwhich consists of two phases: a vapor phase and a liquid phase Propellant has high pressure hence propellant 114 is added to reduce its vapour pressure .

WATER BASED SYSTEMIt is three phase system containing vapour phase, propellant , water. Ethanol used as a cosolvent to solubilize the propellant in water Propellant content varies from 25 -60%

SUSPENSION SYSTEMIt is prepared by dispersion active ingredients in mixture propellant and by using suspending agent The physical stability of suspension can be increased by use 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 SYSTEMThey contain Dispersion of AI,A.Vehicle, surfactant and propellant Liquified propellant used as internal phase Aqueous stable foam : A. Ingredients( antiseptic ) oil waxes O/W surfactant Water Hydrocarbon Non aqueous stable foam : These are prepared by using Glycols Emulsifying agent used this type PEG Esters Quick breaking foam : the product is dispensed a s a foam which then collapsed in to liquid Useful foor topical medication

TYPES OF AEROSOLS DELIVERYNebulizers 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.

NEBULISERIt 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 Drugs are not conveniently prepared by MDI/ DPI

NEBULIZERS

JET NEBULIZERSIt is powered by high pressure airNebuliser commonly used in hospital and home for drug administration have small medication reservoirs(