Innovation in aerosolsPrepared by ; Jenisha Timbadiya(25)Topic: Dry powder inhalerAtmiya institute of pharmacy

Dry powder drug delivery• There are many route of administration but oral is

more preferrable ‘cause it’s non-invasive, convenient & painless so orally inhaled therapy have been developed.

• Instead of giving dry powder doses like tablets & capsules orally, inhalation of those dry powder doses is more better as it not required diffusion, absorption, metabolism it will directly absorbed in blood through lung tissue.

• Many advantages of drug delivery by inhalation like large surface area of lung provides efficient drug absorption

• Inhalation of dry powder is simple & convenient & gives quick action of drug can be obtained

Dry powder inhaler: introduction

• DPIs are devices through which a dry powder formulation of an active drug is delivered for local or systemic effect via the pulmonary route

• DPIs are used to treat respiratory diseases such as asthma, COPD, bronchitis etc.

• For inhalation dry powder particles must be sized less than 5µm whereas for systemic effects particle size of less than 2µm is needed for drug deposition in the small peripheral airways.

HISTORY In 1956 MDI was invented for

asthma Inhalation of medication since

1950s In 1967 DPI started to use In 1988 in DPI multidose device

TURBUHALER was introduced

An ideal DPIEffective dosing• Targeted & optimized delivery • Operable at low inhalation flow rates• Uniform doseEffective device• In process controls for quality• Good enviornmental production • Compact, portable, cheap & reusableEasy to use

Factors to be considered to improve dry powder drug delivery through inhalation:

• Powder production/powder properties • Powder formulation• Dry powder inhaler device.

Powder properties:• Particle size:

generally 2-5µmfor alveoli penetration max size 3 micron & not less than 1

micron for free flowOver micronised powder creates problems like improper

powder flow & forms deagegated cloud • pH• Surface rotation• Surface morphology & surface energy is important

for free flowing & formation of segregation cloud• Crystallinity & polymorphism• Moisture content & hygroscopicity• Polydispersity• Surface area

Formulation of powder drug for DPI

a) Active p’ceutical ingredient

• Therapeutic protein, insulin, drugs to treat bone disorders, vaccines

• Drugs for asthma & chronic obstructive pulmonary disease like β2 adrenergic agonists, corticosteroids, cromones & anticholinergic)

• API of micron size formulated with or without carrier

b)excepient• To improve flow

properties & to prevent agglomeration

• Ex. Lactose, glucose, mannitol

Currently, lactose is the only excipient used in DPIs.

Lactose is highly crystalline & has the smooth surfaces & satisfactory flow properties desirable for a DPI carrier particle.

One drawback of lactose is that it is a reducing sugar, which makes it incompatible with drugs that have primary amine moieties.

Excipients are not always required, the Pulmicort , Astrazeneca (Budesonide) Turbuhaler is an example of an excipient free formulation.

Why lactose is used???

Principle of operation

When patient activates the DPI & inhales

Airflow through the device creates shear & turbulence

Air introduced into the powderbed & static powder blend is fluidized then enters the patient’s airway

The drug particles separate from the carrier particles & are carried deep into lungs to excert effects

While the larger carrier particles impact in oropharynx & are cleared

Fate of inhaled drug:1)Deposition in respiratory tract2)Clearance mechanism:DissolutionMucocillary

clearance(MCC)Macrophage

uptakeTranslocation

DPI device• DPI design must be coordinated with

the formulation of drug• Performance of drug & reachness of

drug to lungs not only depends on powder formulation but also on the inhaler device.• Mouthpiece is critical parameter.

Classification of DPI deviceSpinhaler

Rotahaler

Handihaler

Aerolizer

Single-

unit

dose device

Turbuhaler

Twisthaler

Easyhaler

Clickhaler

Accuhaler/Diskus

Multi

dose

reservoir devices

Aerohaler

Diskhaler/Rotadisk

Multi unit

dose devices

1)Single unit dose systems:Unit dose systems package drug powders into individual use package that contain a known qty of drugex. Spinhaler, rotahaler, Handihaler, Aerolizer

a)Spinhaler: In it capsule is

placed into a holder located on top of a propeller.

The walls of capsule are pierced by two spears when the patient primes the device by sliding a cam. spinhalerTM

Spinhaler

b)Rotahaler:• Insert capsule into

rotahaler• Twist it to break the

capsule• Inhale deeply • Several breath may

be required. • No coordination of

aerosol required• After use,empty

gelatin capsule removed & replaced by another capsule

c)Handihaler

d)Aerolizer

2)Multi dose reservoir devices• Reservoir systems offer the advantage of

variable dosing, generate less waste, are less expensive to manufacture & are simpler to use than unit dose systems.

• Maintaining a highly flowable drug powder in this system leads to greater drug formulation challenges.

• This contain a bulk supply of drug from which individual doses are released with each acutation.

• The first such inhaler to be develop was Turbuhaler.

• Other ex. Twisthaler, Easyhaler, Clickhaler, Accuhaler.

1)loading dose:• While loading, it must be in

upright position.• Twist the bottom colored grip

fully to the right side, twist it back again to left.• There will be sound of click.2)inhaling the dose:• Keep it in horizontal position.• Inhale for 10 sec.• There is window for dose

indicator onto device.

a)Turbuhaler

b)Twisthaler

c)Accuhaler/ Diskus

3)Multi-unit dose devices• Multi unit dose DPIs utilizes

individually prepared & sealed doses of drug.• The first develop was aerohaler which

contained six unit dose capsule each delivering one dose of drug.• Ex. Aerohaler, Diskhaler

a)Aerohaler:To load:• Lift up the mouthpiece to

open• Lift the magazine up

slightly & turn it round in a clockwise direction until mark 6 lines up with the on the base. Push magazine down again

• Load the capsules into the magazine. Push the mouthpiece down until it clicks

To use:• To inhale hold it upright.

Push the button, on side of inhaler until it clicks, it pierces the capsule.

• Breath out, put mouthpiece in mouth, breath in as deeply as possible, remove aerohaler from mouth, hold breath for 10 sec, breath out.

• Turn the magazine for next dose.

• Reload magazine when all capsules have been used.

Aerohaler

b)Diskhaler/Rotadisk

Device drug1)Rotahaler Albuterol/salbutamol,

beclomethasone Handihaler Tiotropium Aerolizer Eformoterol2)accuhaler/Discus Albuterol/salbutamol,

beclomethasone, c Clickhaler Albuterol/salbutamol,

beclomethasone Easyhaler Albuterol/salbutamol,

Beclomethasone Turbuhaler Budesonide, Formoterol,

Terbutaline3)Aerohaler Fenoterol, Ipratropium

bromide Diskhaler/Rotadisk Albuterol/salbutamol,

Beclomethasone, Albuterol/salbutamol,beclomethasone

Current DPI producing brandsGold®Astra®Asmanex®Seretide®Relenza®Bochringer Ingelheim®Symbicort®Mankind®

Advantages of DPI• Little or no patient coordination is required• Convenient & easy to use• Propellent free design as this is toxic in nature.• Onset of action without need for absorption,

digestion, circulation of drug because direct absorption from alveoli to blood for systemic effect

• Quick relief in case of bronchodilation • Spacer is not required• Higher lung deposition than pMDI.

Disadvantages of DPI• Dependency on patient’s inspiratory flow

rate.• Device resistance & other design issues

like mouthpiece is critical for inhalation.• Not available world wide.• More expensive than pMDI.• Dose uniformity problems.• Development & mfg are more expensive &

complex.• Most type are moisture sensitive. Humidity

potentially causes powder clumping & reduced dispersal of fine particle mass.

• Need to reload capsule each time.

• Apperance & colour• Microscopic evaluation• Microbial limits• water/moisture content• Assay(drug content determination)• Particle size analysis• Drug content per unit dose / dose delivery• Average fill weight per capsule• Impurities & degradation products

Evaluation in DPI

Initially inhalation therapy was used only for pulmonary diseases like asthma.

But from past few decades it is used in Cystic fibrosis, Chronic obstructive pulmonary disease as well as in systemic diseases like Irritable bowel syndrom, Schizophrenia, Migraine, Diabetes, Obesity

Recent progress in non-pulmonary indications includes:

Staccata® filled by Loxapine – Schizophrenia – US

Afrezza® - diabetesInavir® - influenza - Japan

References • www.sciencedirect.com• www.medscape.com• Wikipedia.org• Newman sp – aerosol drug delivery, deposition &

clearance studies• Mankind.co.in• J. hickey – p’ceutical inhalation aerosol technology• Remington – the science & practice of pharmacy• COPD at your fingerprint by John miles & June

robert

THANK YOU!!!!!