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AEROSOL

SUBMITTED BY

V.SUHASINI

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Delivery of drug by the pulmonary route

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INTRODUCTION Background & historical perspective Physicochemical factors governing lung deposition

Physiological and anatomical features governing lung deposition

Mechanism of drug clearance and pharmacokinetics of disposition

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Inhaled therapies have existed for at least 5000 year

Modern drug therapy can be traced to the propellant driven metered dose inhaler (pMDI) of the 1950

1990 actively alternative methods of delivering macromolecular drug

Which were difficult to deliver in therapeutic doses by the oral or parental route

Background & Historical perspective

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The physicochemical properties of the droplet or particles being delivered the mechanical aspect of aerosol dispersion

Aerosol are aerodynamic properties Size of particle Visual examination Surface area measurement Equivalent volume diameter Shape and density is the important role

Physicochemical factors governing lung deposition

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Thermal settling velocity measure this formula

Pharmaceutical aerosol high level of rotational symmetry and spherical behavior

Aerosol are hydroscopic nature Rise to a kinetic reaction change in particle

size so transit though the high humidity environment of the lungs ( 99.5% RF at 370C )

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Physiological and anatomical features governing lung deposition

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Estimate of the length, cross sectional, linear velocity of airway indicating the lungs

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Respiratory rates volumes in laboratory animals

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Respiratory rates volumes for healthy young men

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The mechanism of drug clearance from the airway must be considered

Mainly involved mucociliary transport , absorption and cell mediated translocation

The nature of the mechanism involved and the interaction with the aerosol particle complicate the pharmacokinetic of drug clearance from the lungs

The site of deposition in the lungs the nasal, oropharyngeal, tracheobronchial and pulmonary region

Mechanism of drug clearance and pharmacokinetics of disposition

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In this topic discussed about droplet formation may be characterized in term of the nature of the propulsive force and liquid being dispersed

Different type of inhalersA. Propellant driven metered dose inhalers B. Dry powder C. Nebulizers

Categories of aerosol delivery device

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Several key componentsa) Propellants b) Drugsc) Co solventsd) Surfactants Propellants are CFCs

(chlorofluorocarbons), hydrofluoroalkanes and alkenes The vapor pressure and density of

propellants mainly involved in formulation

Propellant driven metered inhalers

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The vapor pressure is the force of emission of the droplet from the metering valve of the inhaler

A co solvent - ethanol surfactants are sorbitan , trioleate , oleic

acid

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Valve and actuator Majority of product marketed by plastic

coated glass or aluminum container The performance should be evaluated in

terms of drug and component physical and chemical compatibilities

Temperature , humidity and stability of the product should be considered

Container and components

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Marketed product of inhaler

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The forces of interaction between particles present barrier to their flow and dispersion

The major forces of interaction are 1. Vander waals force 2. Electrostatic 3. Capillary force The dry powder is delivered for local and

systemic effect via to the pulmonary route The dry powder for inhaler are formulated

loose agglomerates Size range less than 5μg

Dry powder inhalers

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Dry powder inhaler are rapid action Portable ( essay to handle) Good bioavailability

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Dry powder inhaler available in 1. tablet 2. Capsule 3. Reservoir system

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Marketed product of dry powder inhaler

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Nebulizer formation conforms to sterile product preparation

Sufficient used antimicrobial agent in the formulation , notably benzalkonium chloride

The solubility of the drug important the performance of the solution a selected nebulizer

Component include an energy source (gas , electrical ) a site of energy input to solution(capillary tubes )

NEBULIZER

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Mechanism of delivery device is 1. air blast 2. Air jet 3. Ultra sonic system

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Marketed product used in nebulizer

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Emitted dose The therapeutic effect of aerosol is dependent

upon their delivery to lungs Two unit dose sampler are popular These airborne particulate are sample at a fixed flow rate of 60 L/ min

Characterization of pharmaceutical aerosol

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In vitro characterization General sizing methods In vivo characterization

Impaction is the method of choice for evaluating particle or droplet size delivery from pharmaceutical aerosol system

Stoke volume determine aerodynamic diameter of particles being evaluated

Particle size characterization

In vitro characterization

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Reynold’s number for flow greater than 500 but less than 3000

The linear velocity can be derived from the ratio of the volumetric flow

Method is used to prepare of mono disperse aerosols

I. vibrating orifice aerosol generator II. spinning disc aerosol generator

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It highly accurate sources of monodisperse particle range from 1-200µm

Produces solid or liquid check the droplet uniformity by using a gentle flow of air. Measure size , shape , density and surface area

vibrating orifice aerosol generator 3450

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Measure uniformity To measure particle size of aerosol This method are suggested to for preparing

insoluble particle in 2- 10µm This instrument has proven useful in studies involving the transport and deposition of particle (Ex) the measure the particle deposition In elbow formed in Aluminium tube

spinning disc aerosol generator

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It is a 8- stage , 8- orifice sampler used in environment working areas to measure the size distribution and mass concentration levels of solid particles and liquid aerosols

Andersen 8-stage nonviable inertial sampler

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Which can be used for determine the particle size (aerodynamic size distribution )

4-stage liquid impinger

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Number of alterative sizing methods are available

General sizing method

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In-vivo characterization The Dry Powder Insufflator™ – Model

DP-4M is the world’s only commercially available device that is pulmonary administration of dry powders to mice.

It can be used to administer a wide range of pharmaceutical, biologic, radio-opaque and toxicological powder formulations – from nanoparticles to macro porous particles

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 Dry Powder Insufflator™ – Model DP-4M 

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pMDI asthma therapy was introduced a new product have been developed

The major therapeutic categories are β2 adrenergic agonist , anticholinergics , glucocorticosteroids, and anti inflammatory agents used

Parasympathetic and sympathetic nervous system induced brochodilatation

Efficacy

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Drug delivery to the respiratory tract has been characterized by a increase in knowledge of drug droplet or particle manufacturing , behavior ,aerosol dispersion , lung deposition , clearance

The number of disease for which aerosol therapy may be applicable has increase dramatically

Conclusion

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Modern pharmaceutics fourth edition , revised and expanded , edited by Gilbert S. Banker , Christopher T. Rhodes

printed and bound by Replika press pvt. Ltd. india (pg no) 479-496

Referance

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