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 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).