TAILORING DRY POWDER INHALER PERFORMANCE BY - RCPE

Atomization and Sprays, 20(9):763–774, 2010
TAILORING DRY POWDER INHALER PERFORMANCE
BY MODIFYING CARRIER SURFACE TOPOGRAPHY BY
SPRAY DRYING
Stephan G. Maas, 1 Gerhard Schaldach, 2 Peter E. Walzel, 2 &
Nora A. Urbanetz 3,∗
1 Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstrasse
1, 40225 Duesseldorf, Germany
2 Department of Biochemical and Chemical Engineering, Technische Universitaet Dortmund
Emil-Figge-Strasse 68, 44227 Dortmund, Germany
3 Research Center Pharmaceutical Engineering GmbH, Institute of Process and Particle Technology,
Graz University of Technology, Inffeldgasse 21A, 8010 Graz, Austria
∗ Address all correspondence to Nora A. Urbanetz E-mail: nora.urbanetz@tugraz.at
Original Manuscript Submitted: 12/07/2010; Final Draft Received: 18/11/2010
In order to provide adequate performance of dry powder inhalates with respect to dosing and fine particle fraction,
interparticle adhesion between drug and carrier has to be well balanced. It has to be large enough to ensure attachment
of the active ingredient during powder handling and dosing, but small enough to ensure detachment of the drug from
the carrier on inhalation. In this study, interparticle interactions have been modified by targeting the surface topography
of the carrier or rather the contact area between drug and carrier using spray drying. Because lactose is susceptible to
spray drying, resulting in partial or full amorphicity, mannitol was used here. The spray drying outlet temperature
turned out to be an appropriate parameter to affect surface topography, spray drying at low temperature leading to
smooth particles, and spray drying at high temperature leading to rough particle surfaces. Dosing of the inhalate was
found not to be affected by surface roughness of the carrier. However, the fine particle fraction decreases with increasing
surface roughness. Consequently, the use of mannitol carrier particles exhibiting different surface topographies allows
for modifying interparticle interactions, thereby providing an effective tool for tailoring the performance of an inhalate.
KEY WORDS: dry powder inhaler, dosing, fine particle fraction, mannitol, spray drying, surface
1. INTRODUCTION
The delivery of active pharmaceutical ingredients (APIs)
to the lungs by inhalation allows local as well as systemic
treatment of diseases, and is a very promising way
of drug delivery. Pulmonary drug delivery is the most relevant
route of administration in the therapy of asthma and
COPD (chronical obstructive pulmonary disease) (Cazzola
et al., 2007; Hanania, 2008; Miller-Larsson and Sel-
roos, 2006). Local administration of the drug is advantageous
because it offers the opportunity of dose reduction,
and a faster onset of action is observed in comparison to
systemic treatment.
The European Pharmacopoeia (Ph. Eur., 2008a) lists
three classes of inhaler devices, namely, nebulizers, metered
dose inhalers (MDIs), and dry powder inhalers
(DPIs). The related aerosolization principles are nebulization
of aqueous suspensions or solutions, atomization of
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764 Maas et al.
suspensions or solutions by the use of liquefied propellants,
or dispersion of dry powders in the inspired air, respectively.
A prerequisite of the API particles intended to travel
along the narrow airways and to finally reach the deep
parts of the lungs, is an aerodynamic diameter in the range
of 1–5 µm (Daniher and Zhu, 2008; Labiris and Dolovich,
2003a). Because of their small size, these particles are
quite cohesive and show poor flowing properties. Precise
dosing, which is done volumetrically, however, relies on
adequate flowability. For this reason, the micronized API
particles are attached to coarser carrier particles by a mixing
procedure. Usually the carrier particles have particle
sizes of 50–200 µm, ensuring adequate flowability and
dosing. On inhalation, the drug has to detach from the
carrier in order not to impact together with the carrier on
the upper airways. Therefore, interparticle forces between
APIs and carrier particles are of utmost importance for
the performance of the inhalate. On the one hand, these
forces have to be high enough to ensure powder handling
and dosing; and on the other hand, they have to be low
enough to allow API detachment from the carrier surface
on inhalation.
Much work has been done on the modification of interparticle
forces between API and carrier. According to the
literature, carrier surface modification is an appropriate
method to control these forces, although other parameters
such as particle size and size distribution (Danjo et al.,
1989; Mullins et al., 1992), shape and morphology, and
chemical identity (Podczeck et al., 1996) affect interparticle
interactions. The modification of surface topography
targets the area of contact between the active and the carrier.
Surface asperities may increase the distance and reduce
the contact area between the active and the carrier,
resulting in a decrease of the interparticle interactions on
the one hand (Fuller and Tabor, 1975; Rabinovich et al.,
2000; Rumpf, 1974; Tabor, 1977). On the other hand, surface
asperities may also lead to an increase of the contact
area between the active and the drug, especially when the
scale of the asperities is of a similar order of magnitude
as the particle size of the drug. Whether a decrease or increase
of the contact area is induced depends on the size,
shape, number, position, and distribution of the asperities.
The prediction of the impact of surface asperities is therefore
difficult (Iida et al., 1993).
Most of the commercially available DPI formulations
use α-lactose monohydrate carrier particles (Hersey,
1975; Steckel, 2003). Hence, a lot of work has been published
about the surface modification of α-lactose monohydrate.
For example, surface modification was achieved
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by dispersant removement (Dickhoff et al., 2006; El-
Sabawi et al., 2006a,b; Iida et al., 2001, 2003a; Islam et
al., 2004a,b, 2005; Zeng et al., 2001a). Iida et al. (2005)
and Chan et al. (2003) worked on carrier surface covering.
Another way to control carrier surface properties is
the addition of micronized carrier particles or other micronized
chemical compounds (Adi et al., 2006, 2007;
Guchardi et al., 2008; Iida et al., 2003b, 2004a,b; Louey et
al., 2003; Louey and Stewart, 2002; Podczeck, 1999; Tee
et al., 2000; Zeng et al., 1998, 1999). The surface modification
by milling was studied by Steckel et al. (2006),
Ferrari et al. (2004), Iida et al. (2004b), and Young et
al. (2002). Surface modification by varying crystallization
conditions was achieved by Larhrib et al. (2003a,b) and
Zeng et al. (2000a,b,c, 2001b).
Although α-lactose monohydrate is commonly used as
carrier in dry powder inhalates, it has several disadvantages
such as incompatibility of the sugars reducing aldehyde
group with APIs such as formoterol, budesonide or
peptides and proteins (Steckel and Bolzen, 2004). In addition,
commercially available crystals of α-lactose monohydrate
may show great variability in surface properties
depending on the production process (crystallisation,
milling, sieving), resulting in varying adhesion forces between
the drug and the carrier, and consequently varying
drug detachment (Steckel et al., 2004; Young et al., 2008).
Another drawback of α-lactose monohydrate is related
to its different crystal faces exhibiting different physicochemical
properties and affinity to attached drug particles,
thereby leading to unequal interparticle interactions
between the drug and the carrier and unequal drug particle
detachment from the different crystal faces.
Consequently, carrier particles with equal affinity to
the drug particles over the entire carrier surface are
needed as, e.g., obtained in spray drying. Spray-dried particles
are usually of spherical shape. They have a homogeneous
surface structure, ensuring equal affinity to
the active over the entire carrier surface. Additionly, they
exhibit excellent flowing properties. Unfortunately, αlactose
monohydrate is susceptible to mechanical treatment
and spray drying, resulting in amorphicity and giving
rise to stability problems (Buckton et al., 1998; Price
and Young, 2004), which is a further disadvantage of αlactose
monohydrate. An alternative carrier avoiding the
disadvantages mentioned above is mannitol.
Maas (2009) showed that fairly spherical particles exhibiting
a homogeneous surface are obtained by spray
drying aqueous mannitol solutions. By varying the spraydrying
outlet temperature between 60 ◦ C and 120 ◦ C, he
found that the surface roughness of the particles may be
Atomization and Sprays

Tailoring Dry Powder Inhaler Performance 765
tailored, leading to smooth particles exhibiting an indentation
of their shell at low drying temperatures, and rough
particles showing a hole in their shell at high outlet temperatures.
Independent of the outlet temperature, particles
were hollow and had almost the same particle size. Despite
differences in particle surface morphologies, mannitol
was crystalline and consisted of modification I. Mannitol
has been discussed as an alternative to α-lactose
monohydrate already (Adi et al., 2007; Harjunen et al.,
2003; Saint-Lorant et al., 2007; Steckel und Bolzen, 2004;
Tee et al., 2000). However, no data were reported on the
influence of the surface structure of spray-dried mannitol
on interparticle forces. This study is dedicated to the
investigation of the impact of the surface roughness of
the mannitol carrier on the performance of dry powder
inhalates, such as dosing and in vitro respirable fraction.
2. MATERIALS AND METHODS
2.1 Materials
Mannitol (Pearlitol SD 200) was kindly provided by
Roquette, F-Lestrem. Salbutamol suphate was donated by
Lindopharm GmbH (DE-Hilden).
2.2 Micronization of Salbutamol Sulphate
Salbutamol sulphate representing the active substance
was micronized using the air jet mill 50 AS (Hosokawa
Alpine, DE-Augsburg). The injection pressure was set
to 6 bar, milling pressure to 2 bar, and the feeding rate
was adjusted to 1 g/min. The obtained material exhibits
a mean particle diameter of 1.82 µm (x10 = 0.65 ± 0.02
µm, x50 = 1.82 ± 0.02 µm, x90 = 5.07 ± 0.22 µm). Particle
size distributions were determined using laser diffraction.
2.3 Spray Drying of Mannitol
Aqueous mannitol solutions (15% w/w) were fed into a
spray dryer (Niro Atomizer, Niro, DK-Copenhagen), with
a height of 615 mm of the cylindrical part and 700 mm of
the conical part. The diameter of the cylindrical part was
800 mm. The feeding rate was adjusted to 14 mL/min by
a flexible-tube pump, and the solution was atomized to
small droplets by a rotary atomizer with a rotational speed
of 27,500 rpm (4.9 bar air pressure at the turbine). The diameter
of the atomizing wheel was 50 mm. It contained
24 bores, which were 6 mm in height and 3 mm in width.
The spray-drying outlet air temperature was varied. The
obtained products were stored in desiccators containing
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silica gel until further required. Three batches (A, B, C)
per outlet temperature of 60 ◦ C (mannitol 60 ◦ C), 90 ◦ C
(mannitol 90 ◦ C) and 120 ◦ C (mannitol 120 ◦ C) were prepared.
2.4 Preparation and Content Uniformity of
Ordered Mixtures
Batches of ordered mixtures of 8 g were prepared with the
spray-dried particles using a carrier-to-drug ratio of 99:1.
Half of the carrier material was weighed into a stainless
steel vessel, then salbutamol sulphate, and finally the second
half of the carrier material was added. The powder
was mixed in a Turbula mixer (T2C, Bachofen AG, CH-
Muttenz) at 65 rpm for 90 min and allowed to settle for
2 h before further treatment. First, the content uniformity
of the mixture was determined retaining 12 samples. The
content of the active ingredient was analyzed by HPLC.
For the subsequent aerodynamic assessment of fine particles,
only ordered mixtures with content uniformities of

766 Maas et al.
of the cartridge was filled with powder. Each metered
mass was determined by weighing the inhaler before and
after the discharge.
2.8 Delivered Dose
The delivered dose was determined by discharging 10
doses from the Novolizer multidose inhaler using the
experimental setup described in the European Pharmacopoeia
(Ph. Eur., 2008b). Eighty percent of the volume
of the cartridge was filled with powder. In contrast
to Pharmacopoeia, 10 subsequent doses were examined,
each consisting of five puffs in order to ensure the
proper quantification of the drug. The unit sampling apparatus
was rinsed with 100.0 mL of diluted acidic acid
(pH 3), which then was transferred into an Erlenmeyer
flask together with the filter and ultrasonically treated
(5 min) in order to dissolve the drug potentially present
on the filter. The amount of active was determined by
HPLC.
2.9 Assessment of Fine Particles
The aerodynamic assessment of fine particles (Ph. Eur.,
2008c) was performed using the Apparatus E (NGI, Copley
Scientific, UK-Nottingham). The following preparation
steps were necessary. The small cups of the NGI
were coated with 2 mL coating agent (solution of 5% of
a mixture of glycerol and polyoxyethylene-20-cetylether
(95:5) in isopropanol), the large cups with 4 mL. The preseparator
was filled with 15 mL of diluted acetic acid.
The measurements were performed using 79.3 L/min
flow rate. The flow rate was measured with an electronic
digital flowmeter (Model DFM, Copley Scientific, UK-
Nottingham). Pumps (Typ SHC P3, Typ HC P3) and
the critical flow controller (Model TPK) were also from
Copley Scientific. The ordered mixture was filled in the
powder container of a Novolizer (filling grade 80%),
which was fixed to the throat of the impactor by a suitable
adapter. Fifty doses were discharged into the impactor.
The dose of active ingredient on the stages was
dissolved in 20.0 mL of diluted acidic acid by gently
shaking. The preseparator was rinsed with 50.0 mL of
diluted acidic acid (pH 3) and diluted at the ratio 1:5.
The drug was determined by HPLC. The fine particle
dose is calculated as the dose of active ingredient exhibiting
an aerodynamic diameter of

Tailoring Dry Powder Inhaler Performance 767
TABLE 1: Particle Size Distribution of Mannitol Carrier Particles Spray Dried
at 60 ◦ C, 90 ◦ C, and 120 ◦ C (Determined by laser diffraction before and after
treatment with a Turbula mixer at 65 rpm for 90 min; n = 3, mean ± standard
deviation).
Mannitol 60 ◦ C Mannitol 90 ◦ C Mannitol 120 ◦ C
Before treatment
x10 / µm 3,73 ± 0,50 4,93 ± 0,35 4,89 ± 0,16
x50 / µm 13,53 ± 0,28 13,59 ± 0,19 13,19 ± 0,35
x90 / µm 27,77 ± 1,04 26,48 ± 1,69 23,71 ± 0,12
After treatment
x10 / µm 4,42 ± 0,16 4,62 ± 0,14 5,26 ± 0,14
x50 / µm 13,25 ± 0,34 13,96 ± 0,70 13,08 ± 0,22
x90 / µm 26,78 ± 0,69 27,71 ± 1,19 23,33 ± 0,51
a
b
c
Mannitol 60 °C
20 µm
Mannitol 90 °C
20 µm
Mannitol 120 °C
20 µm
d Mannitol 60 °C
e
f
3 µm
Mannitol 90 °C
3 µm
Mannitol 120 °C
FIG. 1: Scanning electron micrographs of ordered mixtures containing active particles and mannitol carrier particles
spray dried at 60 ◦ C (a,d), 90 ◦ C (b,e), and 120 ◦ C 120 ◦ C (c,f) outlet temperature; each micrograph represents a sample
taken from the second of three batches.
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3 µm

768 Maas et al.
Already at this point, it has to be mentioned, the scale of
the surface asperities is in the same range as the particle
size of the active. This is important because the scale of
the asperities in relation to the size of the drug particles is
decisive for the contact area between the carrier and the
active (Young et al., 2008), with smaller-scale asperities
leading to a decrease of the contact area and the interparticle
interactions, whereas larger-scale asperities result in
an increase.
3.3 Metered Mass and Uniformity of Metered
Mass
The metered mass is defined as the mass of the formulation
metered by the built-in metering system of the inhalation
device. The uniformity of the metered mass, re-
mass / mg
40
20
spectively, dosing was examined by discharging 50 doses
from the Novolizer multidose inhaler using the experimental
setup described in the European Pharmacopoeia
monograph (Ph. Eur., 2008b). Each metered mass was
determined by weighing the inhaler before and after the
discharge (Fig. 2).
Three batches (A, B, C) of each formulation (mannitol
60 ◦ C, 90 ◦ C, 120 ◦ C) were examined, and the mean of
the mass (mean mass) of the 50 doses was calculated for
each batch. The mean and the standard deviation of the
mean mass of the three batches (A, B, C) of each formulation
(mannitol 60 ◦ C, 90 ◦ C, 120 ◦ C) were calculated. They
are given in Fig. 3. There is no significant difference between
the formulations, the mean of the mean mass having
values of 8.0 mg for formulations containing mannitol
60 ◦ C, 6.6 mg for formulations containing mannitol
Mannitol
120 °C
Mannitol
90 °C
Mannitol
60 °C
0
0 10 20 30 40 50
number of the dose discharged
FIG. 2: Metered mass of three batches of each formulation containing mannitol carrier particles spray dried at 60◦C, 90◦C, and 120◦C. mean of the mass / mg
12,00
10,00
8,00
6,00
4,00
2,00
0,00
Mannitol 60°C Mannitol 90°C Mannitol 120°C
FIG. 3: Mean of the metered mass of 50 single doses of formulations containing mannitol carrier particles spray dried
at 60◦C, 90◦C), and 120◦C; n = 3, mean ± standard deviation.
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Tailoring Dry Powder Inhaler Performance 769
90 ◦ C, and 8.9 mg for formulations containing mannitol
120 ◦ C.
In addition, the uniformity of dosing was evaluated by
calculating the coefficient of variation of the mass of each
batch (A, B, C). The mean and the standard deviation
of the three coefficients of variation of each formulation
(mannitol 60 ◦ C, 90 ◦ C, 120 ◦ C) were calculated. The coefficients
of variation are given in Fig. 4. Despite the differences
in surface topography, there is no significant difference
between the formulations, the coefficient of variation
showing values of 27.1% for ordered mixtures with
mannitol 60 ◦ C, 36.2% for ordered mixtures with mannitol
90 ◦ C, and 21.3% for ordered mixtures with mannitol
120 ◦ C. Therefore, even if there was a difference of the
flowability of the pure carriers prior to mixing of the carriers
with the active, the attachment of the drug particles to
variation coefficient of the mass / %
50,0
40,0
30,0
20,0
10,0
the carrier surface must have influenced the surface properties
to such an extent that a similar powder flowability
and dosing was finally obtained.
3.4 Delivered Dose
The delivered dose is defined by the dose of active delivered
to the patient by the inhalation device. In this study,
it was determined by discharging 10 doses from the Novolizer
multidose inhaler using the experimental setup described
in the European Pharmacopoeia (Ph. Eur., 2008b).
In contrast to what is described in Pharmacopoeia, 10
subsequent doses were examined, each consisting of five
puffs in order to ensure the proper quantification of the
drug. The dose of active delivered was determined by
HPLC (Fig. 5).
0,0
Mannitol 60°C Mannitol 90°C Mannitol 120°C
FIG. 4: Variation coefficient of the metered mass of 50 single doses of formulations containing mannitol carrier
particles spray dried at 60◦C, 90◦C, and 120◦C; n = 3, mean ± standard deviation.
delivered dose / µg
0
0
0
0 1 2 3 4 5 6 7 8 9 10
number of the dose discharged
FIG. 5: Delivered dose of three batches of each formulation containing mannitol carrier particles spray dried at 60◦C, 90◦C, and 120◦C. Volume 20, Number 9, 2010
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Mannitol
120 °C
Mannitol
90 °C
Mannitol
60 °C

770 Maas et al.
Three batches (A, B, C) of each formulation (mannitol
60 ◦ C, 90 ◦ C, 120 ◦ C) were examined, and the coefficient
of variation of the dose of each batch was calculated in
order to get a measure of the uniformity of the delivered
dose. The mean and the standard deviation of the three
coefficients of variation of each formulation were calculated
(mannitol 60 ◦ C, 90 ◦ C, 120 ◦ C). They are given in
Fig. 6. There is no significant difference between the formulations,
the mean of the coefficients of variation having
values of 33.6% for formulations containing mannitol
60 ◦ C, 37.8% for formulations containing mannitol 90 ◦ C,
and 18.0% for formulations containing mannitol 120 ◦ C.
Because the coefficients of variation of the delivered
dose are not substantially higher than the coefficients of
variation of the metered mass of the formulations metered
by the built-in metering device of the inhaler, the
poor uniformity of the delivered dose may be attributed
to the inadequate flowability and dosing of the formulations,
which, in turn, results from the small particle size
of the carrier obtained by the laboratory spray dryer. In order
to prepare particle sizes of the carrier between 50 and
200 µm, which are normally used in commercially available
products, larger spray dryers will be used. In contrast,
there is no hint that the poor uniformity of the delivered
dose may have been caused by an arbitrary amount of the
formulation being retained on the walls of the inhaler on
actuation.
3.5 Retained Dose
By relating the delivered dose of active to the metered
mass of the drug (which is calculated from the metered
variation
coefficient or the delivered dose / %
55,0
50,0
45,0
40,0
35,0
30,0
25,0
20,0
15,0
10,0
5,0
0,0
mass of the formulation by multiplying the respective
value with the amount of drug present in the formulation),
a measure of the fraction of drug, which is delivered to the
patient, vice versa retained in the inhaler and the mouthpiece
adapter, was obtained. The amount of drug delivered
is 77% for formulations containing mannitol 60 ◦ C
and mannitol 90 ◦ C, and 78 % for formulations containing
mannitol 120 ◦ C, indicating that the amount retained
also is independent on the surface topography of the carrier
(Fig. 7).
3.6 Fine Particle Fraction
The FPF is defined as the fraction of the active with an
aerodynamic particle diameter ≤5 µm devided by the total
amount of the active found in the impactor, and is an
indicator for the fraction of the active reaching the lower
part of the lungs in relation to the total amount of drug
delivered to the patient. The experiments were carried out
using the experimental setup described in the European
Pharmacopoeia (Ph. Eur. 2008c). Fifty puffs equivalent to
approximately 4 mg of drug were delivered from the Novolizer
device to the NGI. The amount of drug on each
stage was measured using HPLC.
Three batches (A, B, C) of each formulation (mannitol
60 ◦ C, 90 ◦ C, 120 ◦ C) were examined, and the mean and
standard deviation of the FPF of the three batches were
calculated. Figure 8 shows that the FPF decreases from
formulations containing mannitol spray dried at 60 ◦ C
(mannitol 60) to formulations containing mannitol spray
dried at 90 ◦ C (mannitol 90) and finally to formulations
containing mannitol spray dried at 120 ◦ C (mannitol 120)
Mannitol 60 °C Mannitol 90 °C Mannitol 120 °C
FIG. 6: Coefficient of variation of 10 doses of formulations containing mannitol carrier particles spray dried at 60 ◦ C,
90 ◦ C, and 120 ◦ C); n = 3, mean ± standard deviation.
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Tailoring Dry Powder Inhaler Performance 771
fraction of the drug delivered / %
100
80
60
40
20
0
Mannitol 60 °C Mannitol 90 °C Mannitol 120 °C
FIG. 7: Fraction of the drug delivered (equal to delivered dose in relation to the metered dose) of formulations
containing mannitol carrier particles spray dried at 60 ◦ C, 90 ◦ C, and 120 ◦ C; n = 3, mean ± standard deviation.
fine particle fraction / %
80
70
60
50
40
30
20
10
0
Mannitol 60 °C Mannitol 90 °C Mannitol 120 °C
FIG. 8: Fine particle fraction of formulations containing mannitol carrier particles spray dried at 60◦C, 90◦C, and
120◦C; n = 3, mean ± standard deviation.
indicating that drug detachment is enhanced from smooth
carrier particles but impeded from rough carrier particles.
Bearing in mind that the drug particles and the asperities
on the surface of the carrier (Fig. 1) are of similar size
range, drug detachment from the rough surface is disfavored
due to the higher contact area between the drug and
the carrier when the drug is embedded in the cavities of
the carrier surface.
4. CONCLUSION
Modifying the surface topography of mannitol carriers intended
for the use in dry powder inhalers is successful by
spray drying aqueous mannitol solutions. By varying the
spray-drying air outlet temperature, the surface roughness
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of the particles can be modified, with low outlet temperatures
leading to smooth surfaces, high outlet temperatures
leading to rough ones. Despite the differences of the
carrier surface topography, the mass of ordered mixtures
of mannitol carriers and the active salbutamol sulphate,
which is metered by the built-in metering system of a
multidose dry powder inhaler, is not affected. This is attributed
to the prescence of the active at the carrier surface
affecting surface topography to such an extent that, despite
the initially different surface topography of the carrier
itself, the surface properties of the mixtures with the
active will be similar. In contrast, the FPF determined in
vitro, and supposed to correlate with the respirable fraction
in vivo, depends strongly on the surface roughness of
the carrier used. Ordered mixtures containing the active

772 Maas et al.
salbutamol sulphate and spray-dried mannitol particles of
a smooth surface exhibit a higher FPF than those containing
mannitol particles of a rough surface. It is assumed
that the rough carrier surface, the asperities of which are
of the same scale as the particle size of the active, builds
up a higher contact area with the drug, thereby increasing
interparticle interactions and decreasing drug detachment.
Consequently, the use of mannitol carriers exhibiting different
surface topographies allows the modification of interparticle
interactions between the carrier and the drug
in a manner that ensures drug attachment to the carrier on
handling, processing, and dosing on the one hand, but adequate
drug detachment on inhalation on the other hand.
Finally, tailoring of interparticle interactions provides a
tool promising adequate performance of the inhalate, irrespective
of the drug substance, to be transferred into the
aerosol.
ACKNOWLEDGMENTS
This work is supported by the DFG (Deutsche Forschungsgemeinschaft),
SPP 1423. The authors are also
grateful to Lindopharm, D-Hilden, for financial support.
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