Measurements of droplet size distributions from metered dose inhalers with different vapour pressures and contents of surfactant

Measurements of droplet size distributions from metered dose inhalers with different vapour pressures and contents of surfactant

J. Aerosol Scl., Vol. 19, No. 7, pp. 1097 - Ii00, 1988 Printed in Great Brltaln 0021-8502/88 $3.00. + 0.00 Pergamon Press pie M E A S U R E M E N T ...

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J. Aerosol Scl., Vol. 19, No. 7, pp. 1097 - Ii00, 1988 Printed in Great Brltaln

0021-8502/88 $3.00. + 0.00 Pergamon Press pie

M E A S U R E M E N T S OF D R O P L E T S I Z E D I S T R I B U T I O N S F R O M M E T E R E D DOSE INHAT.~RS W I T H D I F F E R E N T V A P O U R P R E S S U R E S A N D C O N T E N T S OF SURFACTANT. K.

B~ckstr6m

A B Draco,

a n d P.-G.

Nilsson

PO B o x 34, S - 2 2 1

00 Lund,

Sweden

INTRODUCTION A l a r g e n u m b e r of d r u g s are d e l i v e r e d to t h e l u n g s b y m e a n s of m e t e r e d d o s e i n h a l e r s (MDIs). A n MDI c o n s i s t s of a c a n i s t e r c o n t a i n i n g the d r u g s u b s t a n c e s u s p e n d e d or d i s s o l v e d in a p r o p e l l a n t m i x t u r e . O p t i o n a l l y , a s u r f a c t a n t is a d d e d to l u b r i c a t e t h e v a l v e and to d i s p e r s e the p a r t i c l e s . U p o n a c t u a t i o n , an a e r o s o l of p r o p e l l a n t d r o p l e t s c o n t a i n i n g t h e d r u g is formed. T h e f r a c t i o n of d r u g d e p o s i t e d in t h e lungs is s t r o n g l y d e p e n d e n t u p o n t h e d r o p l e t size d i s t r i b u t i o n . T h e o p t i o n a l d r o p l e t s i z e for d e p o s i t i o n in the lungs is a few microns.

Figure

i. A s c h e m a t i c

illustration

of an MDI.

METHOD AND MATERIALS The droplet Mastersizer diffraction

s i z e d i s t r i b u t i o n was m e a s u r e d w i t h a M a l v e r n (Malvern Ltd, UK). T h e i n s t r u m e n t u s e s the F r a u n h o f e r t h e o r y to e v a l u a t e the d r o p l e t s i z e d i s t r i b u t i o n .

T h e t e s t e d M D I s h a v e the f o l l o w i n g p r o p e r t i e s ; Active

drug:

Surfactant:

Pressure

Terbutaline

sulphate

I0 mg/ml.

S o r b i t a n t r i o l e a t e (Span 85), 2.8 m g / m l or 14 mg/ml.

of p r o p e l l a n t mixture: 410 kPa or 572 kPa.

The terbutaline sulphate 2.1 u m and are s u s p e n d e d

particles have a mass median in the p r o p e l l a n t m i x t u r e . 1097

diameter

of

1098

K. BACKSTROM and P.-G. NILSSON

I~,,(:,:f~,:, ( . t orl [li yt,~r,¢:(:

ll(:a~.rcd /,),,e o f S:'I"&lJ

N

H

.. -

/ /Inahj:;er

[leasurcr~en

Z])ra~I Mozz le

[h:,~m 9 ~ , , .

I'l i . t ( : r

F i g u r e 2. A s c h e m a t i c arrangement.

illustration

Co~puter

of the e x p e r i m e n t a l

RESULTS

1o~[AIF.J~I HasteeStzee $2.~ M a s t e e Rode ............................................................................... 1~. i

,

~

~

::::::

:

I

0.2

:

Date

: ::::::

>:, Spare

26-08-88 ~

~

~

Tine

09-42

J ~ , ~

1

t

,

x

12tl

[

25 ~s

5t

I 18 572 kPa

.1

1

10

Paelic]e

F i g u r e 3. A t y p i c a l

size

lO0

(P.).

size d i s t r i b u t i o n

from an MDI.

~--~

o,z~sp~n41o~P~ to*,, Span 4~0 kP~ i,o,~ S w n ST1 ~pa

Figure MDI.

i

i

i

5

la

15

i

25

i

15

4. The m a s s m e d i a n d i a m e t e r

sO T,me{ms)

for the d r o p l e t s

9 cm from the

Droplet slze distributions from metered dose inhalers

1099

Droplet size (~m) ~--~ 7

0,2% Span 410 kPa

--

~

0,2% Span S73 kea

a

1,0% Span 410 kPa

6

1,0% Span $73 Kpa

$

4

]

~ . _ _ _

--_. . . . . . . .

~

65

80

2

1

0 ~$

50

F i g u r e 5. T h e m a s s m e d i a n d i a m e t e r t h e MDI.

T~me (ms)

for t h e d r o p l e t s

~--~

20 c m f r o m

0,2% Span 41o kPa

- - ~

0,2% Span ST] kPa to',~ Span 4 ~0 ke* I,o% Span 5"13Kpa

"qk-~

lo

ao

30

40

so

~',me (ms)

F i g u r e 6. T h e o b s c u r a t i o n of the d r o p l e t s 9 cm f r o m t h e MDI. o b s c u r a t i o n is a m e a s u r e of t h e c o n c e n t r a t i o n of d r o p l e t s .

The

Obscured,on (',;) ~--~

0,2~ Span 410 kPa

~--~ •

02q6 Spa. S73 k e , ~

t O ~ S~a.410kP* 1,o~ S~*n S73 ~pa

~0

a.O

6O

EO

100

Time(ms)

F i g u r e 7. T h e o b s c u r a t i o n of t h e d r o p l e t s 20 cm f r o m t h e MDI. o b s c u r a t i o n is a m e a s u r e of the c o n c e n t r a t i o n of d r o p l e t s .

The

Ii00

K. BACKSTROM and P.-G. NILSSON CONCLUSIONS * The c o n c e n t r a t i o n of s u r f a c t a n t the d r o p l e t size distribution.

has only a m i n o r

influence

on

* The p r e s s u r e has a large i n f l u e n c e on the d r o p l e t size d i s t r i b u t i o n , a h i g h e r p r e s s u r e gives a s m a l l e r d r o p l e t size. This is b e c a u s e m o r e energy is p r e s e n t to a t o m i z e the p r o p e l l a n t m i x t u r e to small d r o p l e t s w h e n an MDI w i t h a h i g h e r p r e s s u r e is actuated. * The great m a j o r i t y of the p r o p e l l a n t e v a p o r a t e s v e r y rapidly. A f t e r 20 ms the d r o p l e t s have o b t a i n e d t h e i r final size. T h e r e a f t e r they m a i n l y consist of m i c r o n i z e d d r u g p a r t i c l e s glued t o g e t h e r w i t h surfactant. * The c o n c e n t r a t i o n of d r o p l e t s (the obscuration) is d e p e n d e n t upon the c o n c e n t r a t i o n of surfactant, but i n d e p e n d e n t of the p r e s s u r e of the p r o p e l l a n t s in the MDI. * The o b s c u r a t i o n for the d r o p l e t s with the low c o n c e n t r a t i o n of s u r f a c t a n t is a p p r o x i m a t e l y half of the o b s c u r a t i o n for the d r o p l e t s w i t h the h i g h c o n c e n t r a t i o n of surfactant. The d r o p l e t s in the two cases contain active d r u g and s u r f a c t a n t in a p p r o x i m a t e l y the same p r o p o r t i o n s (13 mg/ml vs. 24 mg/ml). This shows that the d r o p l e t s c o n t a i n v e r y little p r o p e l l a n t (except for i m m e d i a t e l y after the actuation).