Overview of pulmonary drug delivery system

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Pulmonary drug delivery system includes the delivery of the drugs through lungs. This system is widely used presently for delivery of peptides and proteins. As the surface area of lungs is large it enhances the absorption. However the concentration of drug deposited does not reach the therapeutic value.
The present presentation includes
> Introduction
> Historical review
> Advantages and disadvantages
> present scenario
> anatomy of respiratory tract
> mechanism of drug absorption
> particle deposition and the factors influencing
> devices for delivering the drugs
> routes of administration
> drug carriers

Key words: particle deposition, drug carriers, drug absorption, liposomes,nanoparticles, surfactants

Profile page link of the author: http://www.pharmainfo.net/hemasree

Profile page link of the guide: http://www.pharmainfo.net/akiladinesh

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Comments

Abhishek Rathi's picture

Dear, Good efforts, As you mentioned in Slide No. 46, that it will be a cost effective method, but if you see the overall cost of the delivery system, it will be comparatively higher than other route. Is it really cost-effective & how? Regards

Abhishek Rathi

G N S HEMA SREE's picture

These days there is high prevalence of diseases like asthma and COPD in soceity, and the studies of using inhaled drugs in these cases have shown a cost effective in terms of direct health care costs (hospitalization,medication)and mainly in DPI reference: Drug Delivery to Lungs by Hans Bisgaurd, chiris O callaghan , Gerald C smaldone page no: 162

G.N.S.Hemasree

Abhishek Rathi's picture

Dear G.N.S. Hema sree, Thanks for the answer. Overall cost will be effective no doubt as you mentioned, but comparatively drug therapy will be higher, thats why I raised that query as we're dealing with formulation aspects. Your answer is satisfactory. Thanks & Regards

Abhishek Rathi

SS Md Shafi's picture

WHAT IS THE ROLE OF BROWNIAN MOTION IN PDDS..??

shafi ..

G N S HEMA SREE's picture

1.Collision and bombardment of small particles by molecules in the respiratory tract produce Brownian motion. As a result the particles move from high to low concentrations causes them to move from the aerosol cloud to the airways walls. The rate of diffusion is inversely proportional to the particle size. so smaller particles gets easily deposited and loss of medication can be minimized REF:" PHARMACEUTICS-THE SCIENCE AND DOSAGE FORM DESIGN' by Aulton

G.N.S.Hemasree

G.Sailesh's picture

1) What is aerodynamic diameter, aerodynamic filter of lungs and their significance? 2) What are the carriers used in DPI and their significance? 3) Can the liposomes administered by pulmonary route and what is the advantage in doing so? Give me an example 4) What is the use of surfactants in pulmonary drug delivery
G N S HEMA SREE's picture

mostly lactose monohydrate is used but it reacts with some drugs like formeterol,budesonide,peptides. So, for that reason other carriers like manitol,glucose,sorbitol,xylitol are used among these manitol shows better drug deposition. SIGNIFICANCE-high dispersibility,actuation of dose is acheived REF-1)artile ALTERNATIVE SUGARS AS POTENTIAL CARRIERS FOR DPI-SCIENCEDIRECT 2)article POWDER PROPERTIES AND THEIR INFLUENCE ON DPI OF ANTI-TUBERCULAR DRUG LIPOSOMES-especially used in jet nubulizers.Drugs encapsulated in liposomes are protected from premature degradation by proteolytic enzymes. SIGNIFICANCE-aqueous compatibility,sustained release,facilitates intracellular delivery to alveolar macrophages,prevents local irritation,minimizes clearance. Eg:cyclosporin A REF- 1)"nano particles as pulmonary drug delivery system to treat and to diagnose respiratory and non-respiratory diseases" article 2)article "recent advances in novel drug delivery system" www.azonano.com

G.N.S.Hemasree

G N S HEMA SREE's picture

surfactants enhances pulmonary absorption of drugs like insulin. A hydrophilic shell protects the content from reticuloendothelial system where they get eliminated from blood stream. These also exhibit low toxicity as they donot cause severe mucous damage REF- article- "nanocarriers as pulmonary drug delivery system to treat and to diagnose respiratory and non-respiratory diseases"-www.ncbi.nlm.nih.gov

G.N.S.Hemasree

G N S HEMA SREE's picture

as i have stated in slide no 24 the aerodynamic size refelcts the deposition locality of drugs in lungs which is very important in delivering drug and it is relates particle diameter and density of particles. Coming to aerodynamic filters, these are a kind of physical defenses shown by lungs generally these filters the particles present in inhaled air also filters the drugs or medication. So prior formulating the drug one has to concentrate on aerodynamic size of the particle in order to passthrough the aerodynamic filters and acheive the target place REF: "oxford textbook of medication" volume:3 by David.A.Warell

G.N.S.Hemasree

Harsh bansal's picture

in slide no 19 u said their is no effect on gravitational sedimentation is in depend on flow of air but i think sedimentation is reciprocal to flow rate what u think? because if particle size is

harsh bansal

G N S HEMA SREE's picture

in this point i too doesnot have much idea but it is stated in that way in the book "drug delivery to lung" by chris o callaghan. please go through it you can get

G.N.S.Hemasree

Harsh bansal's picture

you said if particle is

harsh bansal

G N S HEMA SREE's picture

particles of size less than 2microns are easily deposited in alveoli and also rapidly cleared by air, so the best range is 3-5 microns and as the diameter of blood capillaries is 4microns so partilces of size less than 4microns enters the systemic circulation and 3-5 microns is best range for alvoeli deposition. REFERENCE-" PHARCEUTICS-THE SCIENCE AND DOSAGE FORM DESIGN" BYE M.E.Aulton

G.N.S.Hemasree

G N S HEMA SREE's picture

as i have stated in slide no 24 the aerodynamic size refelcts the deposition locality of drugs in lungs which is very important in delivering drug and it is relates particle diameter and density of particles. Coming to aerodynamic filters, these are a kind of physical defenses shown by lungs generally these filters the particles present in inhaled air also filters the drugs or medication. So prior formulating the drug one has to concentrate on aerodynamic size of the particle in order to passthrough the aerodynamic filters and acheive the target place RERF: "oxford textbook of medication" volume:3 by David.A.Warell

G.N.S.Hemasree

Pooja Chowdary's picture

Delivery of insulin by this system is cost affordable?

pooja

G N S HEMA SREE's picture

delivery of insulin by pulmonary route mainly by pMDI is not cost effective however steps are in progress to make cost affordable REFERENCE-"Innovations and perspectives of metered dose inhalers in pulmonary drug delivery" article

G.N.S.Hemasree

Sandeep Reddy's picture

hi hema ur presentation is really good 1)how this system is advatageous overthe controlled drug delivary system? 2)weather this system is use ful in the treatment of ANS and CNS disease?
G N S HEMA SREE's picture

1.advantages over other systems:a)very rapid onset of action similar to the i.v. route and quicker than can be achieved with either oral delivery or subcutaneous injections.b)avoid gastrointestinal tract problems such as poor solubility, low bioavailability, GI irritation, unwanted metabolites, food effects and dosing variability.c)enable effective drug targeting to lungs for relatively common respiratory tract diseases such as asthma, emphysema, bronchiectasis and chronic bronchitis. 2. as in slide no 49 ANS drugs like salbutamol for asthma ans COPD, and CNS Drugs like benzodiazepeines for treatment of anxiety and sedation can be delivered REFERENCE-"ENCYCLOPEDIA OF PHARMCEUTICAL TECHNOLOGY" VOLUME-3

G.N.S.Hemasree

Sirisha Pingali's picture

dear hema.. very well depicted presentation. The history part you dealt was very informative. Coming to the query, maximum therapeutic effect is not seen in pdds due to drug wastage. How can we minimize this?? Can spacers avoid this problem?

Sirisha Pingali

http://www.pharmainfo.net/sirisha

Viswanadha Institute of Pharmaceutical Sciences.

www.vnips.edu.in

G N S HEMA SREE's picture

use of breath enhanced nebulizers and dosimetric nebulizers,add on devices like spacers and holding chambers can reduce the wastage to certain extent. of course spacers reduces the drug wastage these are the extension tubes the increases the distance between the orifice and patient's oropharynx so that particles are allowed for deceleration and they also reduces the amount of coordination required on part of patients REF-"Gibaldi's drug delivery systems in pharmaceutical care" By Milo Gibaldi

G.N.S.Hemasree

Pooja Chowdary's picture

what type of surfactants are used in pulmonary drug delivery?

pooja

G N S HEMA SREE's picture

as in slide no 44 the surfactants used commonly are span85, oleic acid, lecithins.if you didnot get your doubt cleared please go through following book REF-"Controlled and Novel drug delivery" by N.K.Jain

G.N.S.Hemasree

Pooja Chowdary's picture

Are there any novel delivery systems being developed to overcome these limitations?

pooja

G N S HEMA SREE's picture

there are several other delivery systems which deliver the insulin in order to overcome these effect one can use other delivery systems-transdermal,transmucosal, smart hydrogels, nasal delivery, oral delivery, and treatment of diabetes with synthetic beta cells, REF- article "Insulin Delivery Systems for Controlling Diabetes"

G.N.S.Hemasree

Pooja Chowdary's picture

1)Pulmonary drug delivery in case of drugs like insulin though very effective possesses toxic effects such as bleeding and bronchial asthma ? 2)Can you suggest some measures to prevent or reduce these instances? thank you.....

pooja

G N S HEMA SREE's picture

insulin contained in CAP-PEG particles delivered by intratracheal instillation or spray instillation appeared to have a longer half-life and possess less toxicity than normal insulin solution REF- article "Evaluation of Novel Particles as Pulmonary Delivery Systems for Insulin in Rats" in "the aaps journal"

G.N.S.Hemasree

Harsh bansal's picture

hello hemasree i want to know that their is any change in therapeutic effect of of drug during cough?

harsh bansal

G N S HEMA SREE's picture

of course there is lot of change in therapeutic effect of drug during cough during cough particles get aggregated in throat and mouth resulting in aglomeration there by decreasing the bioavailability of drug. To decrease this recently large and porous particles are developed to prevent the aggregation and also to acheive the sustained formulations REF-article "Recent advances in pulmonary drug delivery using large, porous inhaled particles"

G.N.S.Hemasree

Arun Kumar Palle's picture

IS it the drug release in systemic manner or drug dumping achieved by this process?
G N S HEMA SREE's picture

the drug release process in pulmonary drug delivery is in systemic manner as the particles get agglomerated/aggregated easily dosage forms are formulated in such a way that release of drug is in systemic manner instead of drug dumping and there are no reports of drug dumping in case of pulmonary drug delivery REF-"Pharmaceutical Technologies for Enhancing Oral Bioavailability of Poorly Soluble Drugs" article

G.N.S.Hemasree

Arun Kumar Palle's picture

What is the effect on O2 or CO2 sensitive drugs due to this system?
G N S HEMA SREE's picture

O2 sensitve drugs are specially formulated using anti-oxidants and are encapsulated in nano carriers O2 and CO2 drugs are preferably not used in this delivery system as they get deteriorrated and converts into toxic substances REFERENCE-"Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases" by Malgorzata Smola,1,2 Thierry Vandamme,1 and Adam Sokolowski2

G.N.S.Hemasree

Arun Kumar Palle's picture

The use of this system has an direct effect in damaging the alveoli? then??????????????
G N S HEMA SREE's picture

this is one of the disadvantage in the pulomonary drug delivery to overcome this drug encapsulation in vectors have shown a beneficial effect. Mainly encapsulation of drug in 9NC-liposomes have shown a minimal damage of alveoli REF-"Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases"

G.N.S.Hemasree

Arun Kumar Palle's picture

Is this system useful when the patient is on ventilation? What is the effect on rate of absorption during difference in rate of respiration? Then prolonged exposure to the mucous secretions also decreases drug absorption or not?
G N S HEMA SREE's picture

This system is useful even during mechanical evntilation but some parameters are to be altered. Nebulizers highly influences the efficiency of aerosol generation and aerosol drug delivery during mechanical ventilation Factors such as residual drug volume, particle size, method of generation differentiate aerosol delivery efficiency. Ventilator settings such as ventilation mode, peak inspiratory flow, flow pattern, inspiratory-expiratory ratio affect aerosol delivery and deposition during mechanical ventilation. increase in rate of respiration dilutes the aerosol and increases the wash-out of aerosol into the expiratory limb between breaths. Prolonged exposure to mucous secretions diverts the delivery route of drug. REF-" Article: Influence of nebulizer type, position, and bias flow on aerosol drug delivery in simulated pediatric and adult lung models during mechanical ventilation."

G.N.S.Hemasree

Pooja Chowdary's picture

What is the current scenario of pulmonary drug delivery system? exlain briefly

pooja

G N S HEMA SREE's picture

Researchers at various academic institutions are working on a novel concept to deliver drugs to diseased lungs by using perfluorocarbon liquid which dispels the edematous fluid by drug dissolved perfluorocarbon liquid and eventually spread evenly throughout the airspace of lungs. This would result in distribution of drug throughout the lung and will provide higher local tissue concentrations than with aerosol-borne drug particles. Various therapeutic agents (adenosine, adenosine triphosphate, and nitric oxide) are currently under investigation to be delivered by this technique. Another technique is under development to use a respiratory spray to treat lesions appeared in the mucous membranes of smoker's lungs. Retinoids are effective against lung cancer but in pill form retinoids produce harsh side effects so. A novel dosage form is sought to administer retinoids locally than in the pill that acts throughout the body. It may be more effective since it allows up to 100 times more active substance to be delivered to the diseased lungs. Aradigm has developed AERx pulmonary technology, which would help in delivering morphine and insulin into the lungs. Alkermes has designed an inhalation technology (AIR), which would enable us to deliver efficient dry powder of small molecule, peptide and protein drug particles to the deep lungs. Nektar Therapeutic in conjunction with Pfizer began dosing first diabetic patients for the phase III clinical trial for inhaleable insulin Exubera(r). They are also developing several other active drug molecules to be delivered by using its proprietary delivery technology. several peptide and protein drugs are under are investigated for potential systemic absorption through pulmonary system, and that includes insulin, calcitonin, luteinizing-hormone-releasing hormone (LHRH) analogs, granulocyte colony-stimulating factor (rhG-CSF), and human growth hormone (hGH). REF-"PULMONARY DRUG DELIVERY" A Review by Prof. Naushad Khan Ghilzai, Midwestern University, IL

G.N.S.Hemasree

Pooja Chowdary's picture

what are the diseases that are currently being targetted by pulmonary drug delivery?

pooja

G N S HEMA SREE's picture

both systemic and respiratory tract diseases are cured using this delivery system due to its efficeint delivery of the dose diseases like asthma, chronic obstructive lung disorder,cystis fibrosis emphysema are mainly cured and systemic delivery of insulin, morphine,vaccines,antibiotics was acheived REF-" encyclopedia of pharmceutical technology" volume-3

G.N.S.Hemasree

Anil kumar appapurapu's picture

theory based questions 1. what are the defects of glass -spray type nebulizers? 2. Can you give the formula for calculation of aerodynamic diameter

anilkumar

G N S HEMA SREE's picture

1. defects of glass-spray type nebulizer: a) with is type necrotic effect is common b)with the prolonged use malignant change and trauma is rarely seen 2.aerodynamic diameter=geometric diameter*sq.root of particle density REFERENCE-"Radiology",Volume 52 by Radiological Society of North America

G.N.S.Hemasree

Anil kumar appapurapu's picture

1. what is the differences between a. Nominal dose b. Meter dose c. Delivered dose d. Fine particle dose 2. what happens to diffusional displacement if the particle size is increased? thank you

anilkumar

G N S HEMA SREE's picture

1. fine particle dose refers to the fraction of the inhaler output that has an aerodynamic diameter less than about 6mm nominal dose refers to particles of size less than 4.7 mm normal dose and meter dose differs in terms of dose of drug emitted from the inhaler REF-"Pharmaceutical inhalation aerosol technology" By Anthony J. Hickey 2.diffusional transport increases with time and with decreasing particle diameter. It is independent of the particle density.only ultrafine particles (particles smaller than 0.1 mm in diameter) are deposited solely due to diffusion. As the particle size increases the deposition mechanism and there are chances that the particles doesnot reach the alvoeli and gets deposited in upper airways REF- "DRUG DELIVERY TO LUNG" by hans bisgaurd, chris o callaghan

G.N.S.Hemasree

Anil kumar appapurapu's picture

1. explain the significance of Brownian motion in PDDS? 2. which mechanism of release will be for the particles of >0.5 mcm and

anilkumar

G N S HEMA SREE's picture

1.Collision and bombardment of small particles by molecules in the respiratory tract produce Brownian motion. As a result the particles move from high to low concentrations causes them to move from the aerosol cloud to the airways walls. The rate of diffusion is inversely proportional to the particle size. so smaller particles gets easily deposited and loss of medication can be minimized 2.for the particles of size >0.5 &

G.N.S.Hemasree

Harsh bansal's picture

hello hemasree its last day today... its very nice to meet u through this competition your presentation is nice all the best for your future thank you harshbansal23@rocketmail.com

harsh bansal

Pooja Chowdary's picture

ALL THE BEST...

pooja

Abhishek Rathi's picture

Dear Author, All the best. Its been a very nice experience. It was a really awesome and knowledgeable. Thanks & Regards

Abhishek Rathi

Sandeep Reddy's picture

all the best ....................................................and i wish a good luck

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