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PULMONARY DRUG DELIVERY SYSTEM

PRESENTED BY:NIKHIL K. SHETE2nd SEM M- PHARM.

DEPARTMENT OF PHARMACEUTICS RCPIPER, SHIRPUR 2015-16

Introduction Objective Anatomy & physiology of lungs Factors affecting on pulmonary drug delivery system Mechanism of pulmonary absorption Advantages & disadvantages Current technologies Drugs given by pulmonary route: Conclusion References

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CONTENTS:

Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.

Delivery of drugs directly to their site of action reduces the dose needed to produce a pharmacological effect.

As the lung is able to absorb both water and oil into the tissue, this is not a restriction of pulmonary delivery

Carriers like micro particles, nanoparticles, liposomes can be used in lung targeting

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INTRODUCTION

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ANATOMY & PHYSIOLOGY OF LUNG

shortest average pathlength will show greatest peripheral deposition.

In nose breathing particles are deposited in the nose and pharynx, Hence for pulmonary drug delivery, the aerosols are inhaled via the mouth.

Increasing the inspiratory flow rate (IFR) will enhance deposition

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PHYSIOLOGICAL FACTORS PARTICLE DEPOSITION IN THE AIRWAYS

Lung morphology

Oral vs. nasal breathing

Inspiratory flow rate

volume of air inhaled in one breath, the “Tidal volume”.

Increasing the time between the end of inspiration and the start of exhalation increases the time for sedimentation to occur.

Bronchial obstruction result in localized deposition in the larger airways of the TB region.

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Tidal volume

Breath holding

Disease states

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Pharmaceutical factors affecting aerosol deposition

Size and Density

Less than 5 µm sutable & densities of 0.4 g cm−3 are efficiently deposited in the lungs.

Shape

•Particles which are non-spherical will have at least one physical dimension which is greater than the aerodynamic diameter.Particle shape should be uniform.

Density

Large porous particles with physical diameters of 20 μm and

Physical Stability

DPIs may be hygroscopic and,99.5% RH 37 0C greater chance of being prematurely deposited.

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The fate of particles in the airways

Mucus barrier

The first barrier• The thickness of the mucus layer;• Mucus viscosity• Molecular size of the drug—for THE binding molecules to mucus glycoproteins via electrostatic interactions increase contact time

Alveolar clearance

The uptake of particles by alveolar macrophages is a fairly rapid process clearance

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Mucociliary clearance

The mucus not exist as a stagnant layer but is constantly being propelled along the TB airways by the rhythmic beating of cilia on epithelial cells,Drug entrapped in the mucus will be removed from the TB region via mucociliary clearance within a few hours after being deposited.

Fig. Process of mucocillary clearance

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Factors affecting the absorption and metabolism of drugs in the airways

Area & Absorption barrier thickness

The surface area of the airways is approximately 140 m2, greater surface area the absorption of the drug.

Blood supply

•The lung receives 100% of the cardiac output via a network of fine capillaries. •This rich blood supply which promotes rapid gaseous exchange is also beneficial for systemic drug delivery.

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Mechanism of Pulmonary drug absorption

Drug

Transcellular Transport

Lipophilic Drug Absorbed

Paracellular Transport

Hydrophilic Drug Absorbed

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ADVANTAGES

• low dose need due to targeted action because of that reduced systemic side-effects

• Rapid onset of action;

• Avoidance of gastrointestinal upset;

• Avoidance of intestinal and hepatic first-pass metabolism.

• Nasal drug delivery is attractive not because it is BETTER than injectable•It used when a drug is poorly absorbed orally e.g. Na cromoglicate.

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DISADVANTAGES

• Various factors affect the reproducibility of drug delivery to the lungs, including physiological and pharmaceutical (device, formulation) variables.

• limited absorbtion due to physical barrier of the mucus layer and the interactions of drugs with mucus.

• Mucociliary clearance reduces the retention time of drugs within the lungs.

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CURRENT TECHNOLOGIES FOR PULMONARY DRUG DELIVERY

Currently there are three principal categories of aerosol generator employed in inhalation therapy:

• Nebulizer;• Pressurized metered-dose inhaler (pmdi);• Dry powder inhaler (DPI).

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Air-jet nebulizers

Nebulizer Defination ---

Drug solution is drawn from the reservoir up the capillary as a result of the region of negative pressure created by the compressedair passing over the open end of the capillary (Venturi effect).

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Ultrasonic nebulizers

These nebulizers rely on a transducer made from a piezo-electric crystal which produces high frequency sound waves in the liquid.The waves give rise to vertical capillaries of liquid (“fountains”) which, when the amplitude of the energy applied is sufficient, break up to provide an aerosol.

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Pressurized metered-dose inhaler (pmdi)

1. Container

2. Metering valve

3. An elastomer seal

4. The actuator

5. propellant

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Dry powder inhalers (DPIs)

For successful delivery of drug particles into the lung requires that particle size should be controlled to <5 μm

The problems associated with particle size is to use a carrier particle such as lactose. (usually 20–100 μm)

Spinhaler

For Asthma: B-adrenergic agents eg.salbutamol,terbutaline Anticholinergics eg. Ipratropium Br Pulmonary Infections:(Pulmonary aspargillosis) Antibiotics eg. Erythromycin & amphotericine-BCardiovascular agents: Nifedipine,NitroglycerineAntiviral agents: Rebavirin,zenamivir

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DRUGS GIVEN BY PULMONARY ROUTE:

PDDS used becouse of limition associsted with the conventional treatment of verious chronic disease

In this DDS directly act to lung and get systemic and local effect

Modification in PDDS keep going on to modify release profile to over come limitation associate Physicochemical barrier

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CONCLUSION

1. Karhale Ashish A., Chaudhari Hiralal S., Ughade Prajkta L., Baviskar Dheeraj T., Jain Dinesh K. “Pulmonary Drug Delivery System” International Journal of PharmTech Research, Vol.4, No.1, Jan-Mar 2012

2. Chaturvedi N.P.*, Solanki h. “Pulmonary drug delivery system: review”, international journal of applied pharmaceutics Vol 5, Issue 3, 2013

3. ND Shah, VV Shah and ND Chivate, “Pulmonary Drug Delivery: A Promising Approach”, Journal of Applied Pharmaceutical Science 02 (06); 2012

4. Hillery m.,Lloyd w.,2005, ‘Advanced Drug Delivery and Targeting: An Introduction’Drug Delivery & Targeting, 3rd Edition, Taylor & Francis Inc,29 West 35th Street, New York,Page no:244-273

5. Banker s. g.,Rhodes t. c.,2002, ‘Target Oriented Drug Delivery System’Modern Pharmaceutics,4th Edition,United States Of America,Page no:431-480

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REFERENCES

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