Dekati® BOLAR™

Bipolar Charge Analyzer

Jonna Kannosto

Technical Marketing Specialist, PhD

Sales & Marketing

Jonna Kannosto

Content

• BOLAR construction

• Background of charge measurement in inhaler studies– Why charge is important?

– Net charge measurement results

• BOLAR – Operating principle

– How to do measurement

© Dekati Ltd.

BOLAR™ Construction

USP Port connection

Flow divider

Bipolar detector

• Stand alone unit

• Fully automated self check

• Automated test sequence

• Result calculation

• Analysis of collected particles

– Charge per mass

– Chemical analysis

Why particle charge is measured?

Particle charge affects:

- Lung deposition

- Dispersion / agglomeration of

particles

- Particle losses inside the device

- Powder processing and handling

© Dekati Ltd.

Charge can cause problems but can also be useful !!!

Jonna Kannosto

Particles and lung deposition

• Inertial impaction

• Diffusion

• Electrostatic attraction

• Gravitational sedimentation

• Interception

© Dekati Ltd. Jonna Kannosto

Effect of particle charge on lung deposition

Electrostatic charge enhances deposition by increasing

attractive forces towards airway surfaces.• Melandri et al 1987, 1975:

Electrostatic charge affects deposition in two ways

• space charge: – predominant in upper airways

• image charge:– predominant in lower airways

© Dekati Ltd.C

harg

e

Lung

depositio

n

+

+ +

+

+

+++

++

- - - - -

Jonna Kannosto

Particle separation

• Significant for effective aerosol generation

• Main interaction between particles

1. Mechanical interlocking

2. Capillary forces (in the presence of water)

3. Intermolecular interactions

4. Electrostatic forces

© Dekati Ltd. Jonna Kannosto

Contact charging

© Dekati Ltd.

- - - - -

+++++

Drug

_

“Both drugs were found to

profoundly alter the charging

properties of lactose” Elaijnaf et al. J. of Pharm. Sci., 2006

“It is common knowledge that

lactose powders become positively

charged in contact with glass” Karner et al. J. of Aerosol Sci., 2011

“Liquids can also be charged

by flowing against a solid

surface” Philip Kwok, Doctoral Thesis, 2007

Jonna Kannosto

Particle charging: influencing variables

© Dekati Ltd.

Particle size

Particle shapeSurface roughness

Particle material

Surface material

Impurities Amorphicity

Relative humidity

Energy of contact

Nature and work functions(triboelectric series)

+ +

+ + -

-

-

-

Surface of particle

Crystallinity

Jonna Kannosto

++

© Dekati Ltd.

Particle charge measurements

Net charge measurement Bipolar charge measurement

Total net charge

- - - - ++0

3

+

4

-4

-

3

+

1

-

+-

-

5

-

3

+

2

-

vs. size dependent bipolar charge

4

-

3

++-5

-

3

+

1

-Result

vs. size dependent net charge

Jonna Kannosto

© Dekati Ltd.

NET charge size measurements:

ELPI+™ (Electrical Low Pressure Impactor)

• Real-time particle number concentration and size distribution

• Real-time particle net charge distribution

• 14 size fractions

• 6nm – 10µm

Jonna Kannosto

Powder: reliability of production and storage

© Dekati Ltd.

Martin Jan Telko, Investigation of electrostatic charging phenomena in dry powder

inhalers and the effect on deposition, PhD Thesis, 2009

Jonna Kannosto

Net charge/particle

© Dekati Ltd.

Martin Jan Telko, Investigation of

electrostatic charging phenomena in dry

powder inhalers and the effect on

deposition, PhD Thesis, 2009

Based on simulations and

in vivo studies:

• micron-size particles

Effect of drug and excipient

© Dekati Ltd.

Martin Jan Telko, Investigation of electrostatic charging

phenomena in dry powder inhalers and the effect on

deposition, PhD Thesis, 2009

Alb

ute

rol

Budesonid

e

Jonna Kannosto

BOLAR™

Calibration

Jonna Kannosto

© Dekati Ltd.

Operating Principle

USP Port

Flow divider

Impactor stage

Bipolar detector

tube x 5

Flow divider

• Devides flow

• Pre-separator

Impactor

• Size classification

Bipolar detector

tubes

• Detects and collects

• Positively charged particles

• Negatively charged particles

Electrometers measure current

carried by the charged particles

Jonna Kannosto

© Dekati Ltd.

Operating Principle

Bipolar detector

tube x 5

Flow divider

• Devides flow

• Pre-separator

Impactor

• Size classification

Bipolar detector

tubes

• Detects and collects

• Positively charged particles

• Negatively charged particles

ImpactorImpactorImpactorImpactorFilter

Bipolar detector

tubes

Bipolar detector

tubes

Bipolar detector

tubes

Bipolar detector

tubes

Flow divider

Flow divider

Flow divider

Flow divider

Flow divider

Electrometers measure current

carried by the charged particles

Jonna Kannosto

Bipolar detector: operation and construction

© Dekati Ltd.

• Five bipolar detectors:

• five particle size classes

• pre-separator impactors and bipolar

detector tube

• Each bipolar detector tube consists of two

concentric cylinders

• Electrical field (1kV) to separate and collect

positively and negatively charged particles to

inner and outer tubes

• Electrometers connected to tubes measuring

charge carried by particles

• Back-up filters Bipolar Detector Tube

Size range (µm)

1 0 - 0.95

2 0 - 2.60

3 0 - 4.17

4 0 – 7.29

5 0 – 11.57Jonna Kannosto

Calibration paperBipolar Charge Analyzer (BOLAR™): A new aerosol

instrument for bipolar charge measurementsJaakko Yli-Ojanperä, Ari Ukkonen, Anssi Järvinen, Stve M. Layzell, Ville

Niemelä and Jorma Keskinen

Jonna Kannosto

Bipolar Charge size distribution

© Dekati Ltd.

J Kannosto, H Isherwood, V Niemelä, A Ukkonen, High Bipolar

Electrical Charge Levels of Lactose Particles Measured from DPI, RDD

Europe 2013 (2013), Vol. 2, pp. 285-290

Capsule based DPI, Lactose particles, 60L/min flow rate, T=20Cº, RH=50%

Lactose particles present much higher positive and lower negative charge

values than measured net charge values

→ More precise information about charge state of particles

Jonna Kannosto

© Dekati Ltd.

Bipolar Charge/Mass size distribution

After the charge measurements, mass of particles were analyzed

• Small lactose particles have larger absolute charge/mass ratio

• Charge/mass ratio decreases when particle size increases

J Kannosto, H Isherwood, V Niemelä, A Ukkonen, High Bipolar

Electrical Charge Levels of Lactose Particles Measured from DPI, RDD

Europe 2013 (2013), Vol. 2, pp. 285-290

Jonna Kannosto

Conclusions

• Electrical charge of particle has effect on– Lung deposition

– Particle separation

– Particle losses inside the device

• Results from NET charge measurements– Drug and carrier

– Inhaler

– Storage

– Relative humidity

– …

→ All these have effect on particle charge

• Based on BIPOLAR charge measurements– Particles can have much high positive and negative values even net charge is zero

– Unique information about charge state of particles

© Dekati Ltd. Jonna Kannosto