Accepted Manuscript

Title: Investigation of chemically modified inulin as

encapsulation material for pharmaceutical substances by
spray-drying

Authors: Michael Walz, Thomas Hirth, Achim Weber

PII: S0927-7757(17)30730-6
DOI: http://dx.doi.org/doi:10.1016/j.colsurfa.2017.07.072
Reference: COLSUA 21846

To appear in: Colloids and Surfaces A: Physicochem. Eng. Aspects

Received date: 29-9-2016

Revised date: 24-7-2017
Accepted date: 24-7-2017

Please cite this article as: Michael Walz, Thomas Hirth, Achim Weber, Investigation of
chemically modified inulin as encapsulation material for pharmaceutical substances
by spray-drying, Colloids and Surfaces A: Physicochemical and Engineering
Aspectshttp://dx.doi.org/10.1016/j.colsurfa.2017.07.072

This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
 COLLOIDS AND SURFACES A: PHYSICOCHEM. ENG. ASPECTS

Available online at www.sciencedirect.com

Journal homepage: www.elsevier.com/

Formula VIII

Investigation of chemically modified inulin as encapsulation material for

pharmaceutical substances by spray-drying

Michael Walza, Thomas Hirthb, Achim Webera,c*

a University of Stuttgart, Institute of Interfacial Process Engineering and Plasma Technology IGVP, Nobelstraße 12, 70569 Stuttgart, Germany
b Karlsruhe Institute of Technology, Kaiserstraße 12, 76131 Karlsruhe, Germany
c Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstraße 12, 70569 Stuttgart, Germany

ARTICLE INFO ABSTRACT

Article history: The application of inulin as a drug carrier system for dexpanthenol in particles prepared by spray-drying
Received was investigated in this research. First, inulin was chemically modified by esterification of free hydroxyl
Received in revised form groups with acetic anhydride and propionic anhydride. The obtained polymers were purified by
Accepted precipitation and analyzed via NMR, FT-IR, SEC and DSC. In the next step, the spray-drying and particle
formation of native inulin, acetylated and propionylated inulin were investigated in order to optimize the
Keywords: parameters. Each material delivered smooth and spherical particles with a size range from 0.7 µm to
Microencapsulation 10 µm. Subsequently, 1 % dexpanthenol was encapsulated in each material and the release behavior with
Drug release respect to chemical modification was compared. The release behavior of dexpanthenol was determined
Spray-drying using a flow through cell (USP4) with dialysis adapter for microparticles. Inulin particles released 100 %
Propionylation dexpanthenol after 6 hours, while the use of chemically modified inulin derivatives presented a prolonged
Acetylation drug release. After 24 hours, 60 % had been released from particles with acetylated inulin and only 10 %
from those with propionylated inulin.

biomaterials or biopolymers. Besides the continuous release of the drug,

1. Introduction the particles should be (bio)degradable in order to avoid accumulations of
micro- and nanoparticles and cause cytotoxic effects [2].
Adjusting release profiles for oral and parenteral drug applications and The development of new formulations requires different encapsulation
formulations are of high interest. The continuous release of the techniques, depending on the targeted properties of the substance, material
pharmaceutical substance ensures a safer treatment due to lower and application. There are several technologies for the encapsulation and
concentrations and reduced medications [1]. This improves the particle formation available such as polymerization, evaporation and
compliance of the treatment regarding side effects, e.g. in cancer therapy. coacervation [3,4]. Most of the encapsulation methods are solvent based,
The materials for such drug delivery systems have to be biocompatible, requiring costly preparation and purification steps to obtain the desired
especially for in vivo applications. Therefore drugs are encapsulated in product. The usage of polymers is limited by the process parameters in the

* Corresponding author. Tel.: +49 711 970 4022

E-mail address: [email protected]

xxxx-xxxx/$ – see front matter © 2013 xxxxxxxx. Hosting by Elsevier B.V. All rights reserved.
http://dx.doi.org/
2 Colloids and Surfaces A: Physicochem. Eng. Aspects

encapsulation technique, especially biopolymers, which have poor characterized using a temperature range from 0 °C to 200 °C, acetylated
solubility in organic solvents. Spray-drying, however, is a promising and propionylated inulin from -50 °C to 150 °C all under nitrogen
alternative method that allows the processing of biopolymers in aqueous atmosphere.
solutions. In the last decade, bio-based polymers have attracted strong The shape and surface structure of the particles were examined by using a
interest due to sustainability, compliance and economical aspects. Some scanning electron microscope LEO 1530VP (Zeiss). The dried particles
biopolymers, e.g. chitosan [5,6], casein [7], cellulose derivatives [8,9] and were immobilized on an electric conductive tape, whereas the suspended
polyhydroxybutyrate (PHB) [10], have been successfully processed using particles were separately dried on silica wafers.
the spray-drying method. Hence, the spray-drying method can be used as For the formation of particles via spray-drying, the B-290 mini spray-
a cheap, up-scalable and one-step procedure. In this method, the polymer, dryer (Büchi, Switzerland) with a high-performance cyclone was used.
which can be processed as a solution, emulsion or suspension, is atomized The experiments were carried out under nitrogen atmosphere using the
by a nozzle and dried in a hot gas flow. By varying the parameters e.g. closed loop system.
viscosity, feed rate or atomization pressure, it is possible to tailor the Investigating the release behavior, a flow through cell (Erweka DFZ 720,
produced particle size [11]. Besides changing the process parameters, the USP4) with a dialysis adapter (Spectrum Labs, RC, MWCO 3.5 kDa) and
modification of biopolymers, such as acetylation, changes the release peristaltic pump (IPC-Isnatec ISM931A) was used with a PBS buffer
properties of encapsulated substances [12]. (pH = 7.4).
The aim of this study was the encapsulation of dexpanthenol as a The quantification of the dexpanthenol release was determined by high
representative low molecular pharmaceutical substance with inulin as a performance liquid chromatography (HPLC), using the prominence
bio-based, biodegradable polymer using the spray-drying process. system (Shimadzu GmbH). The following parts belong to the HPLC
Furthermore, we investigated the influence of the inulin modifications system: degasser (DGU-20A), pump (LC-20AT), autosampler (SIL-20AC
towards the release behavior of dexpanthenol. Inulin is a nontoxic and HAT), column oven (CTO-20AC) and a photodiode-array detector (SPD-
degradable polysaccharide obtained from plants, such as the chicory root, M20A). As a column the ReproSil-Pur 120 C4 (50 mm x 4 mm; 3 µm, Dr.
and already established as a food ingredient due to its prebiotic effects Maisch GmbH) was used at 40 °C. For the mobile phase, 95 % water was
[13]. Its structure is based on fructose units with one glucose group at the used containing 0.05 % trifluoroacetic acid and 5 % acetonitrile with a
end. The solubility of inulin in water depends on its degree of flow rate of 1.5 mL/min. The calibration curve was measured between
polymerization, which is between 10 and 20. We modified inulin by 25 ppm and 0.78 ppm injecting 100 µL of standard with R² = 0.9999. The
inserting hydrophobic groups aiming to improve the stability of inulin detection wavelength was set to be 200 nm.
particles in water. For that, we used acetic anhydride [12] and propionic
anhydride. Inulin and its derivatives were processed by spray-drying and 2.3. Modification of inulin
the parameters were adjusted to obtain spherical particles and high yields.
Dexpanthenol was encapsulated with a content of 1 % by spray-drying. Acetylated inulin (Ac-In) was synthesized according to Wu et al. and
The obtained particles were characterized by SEM. The release behavior Poulain et al. with changes in the ratio of inulin and acetic anhydride
was tested in a flow through cell using phosphate buffered saline solution [12,14]. Inulin (1 g, 6.14 mmol) and sodium acetate (12 mg, 0.15 mmol)
PBS and analyzed via high performance liquid chromatography. were dissolved in 10 mL DMF and heated up to 40 °C. Acetic anhydride
(5.2 mL, 55.24 mmol) was added dropwise after complete dissolution of
2. Experimental inulin. After 24 h under stirring, the modified inulin was precipitated in an
excess of water and purified via centrifugation. The pellet was dissolved
2.1. Materials in acetone and precipitated again. The procedure was repeated once more
and the resulting precipitate was dried under vacuum overnight. If the
Inulin with a degree of polymerization of 20 was received from the NMR showed residues of acetic acid, the product was dried for another 24
company Georg Breuer GmbH (trade name Fibruline XL). Acetic hours.
anhydride (≥ 99 %), propionic anhydride (97 %), sodium acetate
(anhydrous, for molecular biology, ≥ 99 %) and dexpanthenol (Ph. Eur. Propionylated inulin (Prop-In) was prepared similarly as described above.
Grade) were purchased from Sigma Aldrich. N,N-dimethylformamide Inulin (6 g, 36.8 mmol) and sodium acetate (50 mg, 0.37 mmol) were
(DMF) was obtained from Carl Roth GmbH. Acetone (HPLC grade) and dissolved in 60 mL DMF and heated up to 40 °C. Propionic anhydride
Ethanol (HPLC grade) were not further purified. The chemicals were used (42.3 mL, 331.5 mmol) was added dropwise after complete dissolution of
as received. inulin. After 24 h under stirring, the modified inulin was precipitated in an
Ultrapure water (TKA GenPure) was used to prepare aqueous solutions excess of 1 M NaOH solution. The pH value was adjusted to 8 by adding
and purify the products (herein referred to as water). 5 M NaOH, if necessary. The suspension was stirred for at least 1 h until
complete dissolution of propionic acid. The product was obtained by
2.2. Instruments centrifugation and dissolved in acetone. Subsequently, the polymer
solution was dropped into an excess of water under vigorous stirring. If
The modification of inulin was characterized by 1H-NMR spectroscopy at the pH was neutral, the product was centrifuged, precipitated once more
500 MHz (Bruker Avance 500 spectrometer) in deutero dimethylsulfoxide and dried under vacuum overnight.
(DMSO-d6) standardized to 2.50 ppm. The FT-IR spectra were carried out
with KBr discs in transmission using a Bruker Equinox 55. 2.4. Encapsulation of dexpanthenol by spray-drying
The differential scanning calorimetry (DSC) measurements were
performed using a Netzsch DSC 200 F3 Maia. Each sample was heated up Inulin (990 mg) was dissolved in water at 80 °C and then cooled down to
three times with 5 K/min and a cooling rate of 20 K/min. Inulin was room temperature (RT). Acetylated inulin (990 mg) was dissolved in
 Colloids and Surfaces A: Physicochem. Eng. Aspects 3

20 mL acetone and diluted with 20 mL ethanol at RT. Propionylated vibration of the hydroxyl groups at υOH = 3300 cm-1 for inulin shifts to
inulin (990 mg) was dissolved in 40 mL acetone at RT. For the 3500 cm-1 with a decrease of intensity compared to the modified inulin.
encapsulation experiments, 10 mg of dexpanthenol was added.
The spray-dryer was used in a closed loop system under nitrogen
atmosphere. The air flow was held constant at 35 m³/h (device indicator:
100 %) and the feed rate of 4.5 mL/min (14 %) for all experiments. The
inlet temperature was varied due to the boiling point of the solvent. Inulin
in water was dried at 115 °C, Ac-In in acetone/ethanol at 80 °C and
Prop-In in acetone at 25 °C. The atomization gas for inulin was held at
620 L/h (52 mm) and for the modified inulin at 473 L/h (40 mm). The
obtained particles were dried in a vacuum drying oven and stored under
dry conditions in a fridge at 4 °C.

2.5. Drug release studies

For the investigation of the dexpanthenol release behavior regarding the

chemical modification of the particle matrix, a flow through cell was used.
The particles (100 mg) were enclosed in a dialysis tube and placed inside
the cell. 50 mL of 0.1 M phosphate buffer saline PBS (pH = 7.4) at 37 °C Fig. 1. 1H-NMR spectra of native inulin ( ▬ ), acetylated inulin (Ac-In ▬)
was used and pumped in a closed, circular system. After specific time and propionylated inulin (Pro-In ▬) in DMSO-d6. The inulin backbone signals
are between 6 ppm and 3.3 ppm; the groups of the esterification between
intervals, 500 µL aliquots were taken and analyzed via HPLC at 200 nm.
2.5 ppm and 0.7 ppm.
The removed solvent was not replaced, but considered in the calculation,
having a lower total volume of PBS.
The methyl groups of the ester were found at υCH2/CH3 = 2900 cm-1 and
3. Results and discussion δCH2/CH3 = 1200 cm-1 – 1400 cm-1 in the fingerprint region. The carbonyl
vibration at υC=O = 1750 cm-1 for acetylated and propionylated inulin
3.1. Modification of inulin confirmed the results of the NMR spectroscopy. Determining the degree
of substitution by IR spectroscopy was not possible.
Inulin was acetylated and propionylated in order to adjust the particle
solubility in aqueous solutions and, therefore, to adjust the release
proprieties of encapsulated substances in the particles. The materials were
characterized by NMR, FT-IR, SEC and DSC. After the synthesis,
purification and drying of acetylated inulin, a yield of 90 % was obtained.
In another experiment, the scale up of this synthesis by a 10-fold yielded
the same results. The purification process of propionylated inulin had to
be improved, due to the lower solubility and reactivity of propionic
anhydride in water. Consequently, the polymer solution was dropped into
a 1 M NaOH solution to remove the excessive anhydride. After
purification and drying of propionylated inulin, a yield of 85 % was
obtained.

The 1H-NMR spectra of inulin and its derivatives is shown in Fig. 1 taken
in DMSO-d6 and standardized at 2.5 ppm. The protons of the fructan
group of unmodified inulin ranges from δ = 5.17 ppm (d/m, 1H, methine), Fig. 2. FT-IR spectra of native inulin ( ▬ ), acetylated inulin (Ac-In ▬) and
δ = 4.73 ppm – 4.61 ppm (m, 2H, methine) to δ = 4.06 ppm - 3.50 ppm propionylated inulin (Pro-In ▬) using KBr discs in transmission.
(d/m, 4H, methylene). Acetylated inulin reveals some shifted signals of
the inulin-backbone to δ = 5.55 ppm - 5.08 ppm (t/m, 3H, methine) and δ The DSC was used to analyze the physical changes regarding the
= 4.27 ppm - 3.61 ppm (d/m, 4H, methylene). The new signal at δ = 2.03 modification of inulin, see Fig. 3. Native inulin has a melting point
ppm (s, 3H, methyl) indicates the conversion of the hydroxyl into an between 170 °C and 185 °C, which is explained by different crystalline
acetate group. The propionylated inulin showed the same signal in the morphology [15]. The effect of the modification on the melting point is
range from δ = 5.55 ppm to δ = 3.61 ppm as acetylated inulin. significant. Acetylated inulin exhibited a melting point of 75 °C and
Characteristic signals of the propionate ester were found at δ = 1.01 ppm propionylated inulin of 45 °C. The difference compared to native inulin is
(s, 3H, methyl) and δ = 2.23 ppm (s, 2H, methylene), indicating a 95 °C and 125 °C. Hence, a higher linear sidechain modification leads to a
conversion of the hydroxyl groups. It could be shown, that both lower melting point [16]. This information is relevant for the application
modifications were synthesized with high yield and purity. in the spray-drying process. The outlet temperature of the drying gas after
evaporation of the solvent has to be lower than the melting point of the
FT-IR was used to verify the obtained results of the NMR spectroscopy. material. Otherwise, the particles aggregate and deform, as shown in Fig 5
The spectra of inulin and derivatives are shown in Fig. 2. The stretching [17].
4 Colloids and Surfaces A: Physicochem. Eng. Aspects

The degree of substitution (DS) was calculated via NMR according to Jain nitrogen cycle was required. Instead of pressured air, nitrogen was used as
et al. with the ratio of Hmethyl/3 (δ = 2.03 ppm for acetate or δ = 1.01 ppm atomization gas to prevent an explosive atmosphere in the spray-dryer. In
for propionate) / Hbackbone/7 (δ = 5.55 ppm – 3.61 ppm) [16]. Acetylated the first step, the polymers were spray-dried and the particles were
inulin has a degree of substitution of 2.4, which corresponds to a characterized. Inulin was dissolved in water and processed at 120 °C,
conversion of the hydroxyl groups of 80 %, whereas propionylated inulin obtaining yields between 70 % and 80 %. Spherical, round shaped
has a DS of 2.3 and a conversion of 77 %. An influence on the reactivity particles with size ranging from 0.8 µm to 5 µm were obtained (see
comparing acetic anhydride and propionic anhydride could not be Fig. 7).
observed. Both anhydrides generate the same degree of substitution with In prior experiments, acetone was used for acetylated inulin as solvent
comparable yield. leading to small yields in the range of 6 % to 20 %. The lower yield can
be explained by the smaller particle size using a cyclone for particle
separation. Therefore, a mixture of acetone and ethanol, as well as a
drying temperature of 80 °C was applied to increase the yield. The
increasing boiling point of the solvent mixture and the decrease of the
temperature lead to higher yields of 82 %. The acetylated inulin particles
were found to be smaller than inulin particles, ranging from 0.5 µm to 2
µm, but still had a spherical, smooth shape. (See Fig. 4) If the particle size
is too small, the air flow will stir the particles up. Additionally, the
acetylated inulin particles were investigated regarding their stability in
water. Therefore, a suspension of 10 mg/mL was incubated for three days
in water. Figure 4 shows the swelling behavior of the acetylated inulin
Fig. 3. DSC curves for native inulin ( ▬ ), acetylated inulin (Ac-In ▬) and particles. No indication of dissolution or change of shape was observed.
propionylated inulin (Pro-In ▬) with 5 K/min heating rate. Hence, it could be shown that the particles do not dissolve and the
surfaces do not alter after 72 h.
The molecular weight distribution was determined via size exclusion
chromatography (SEC). Due to the available set up and columns, only the
modified inulin could be determined. The measurement showed a narrow
distribution of acetylated and propionylated inulin with a polydispersity
index (PDI) of 1.25 for both modifications. The molecular weight MSEC,
represented in in table 1, was calculated referring to a polystyrene
standard. In comparison, the molecular weight MNMR was calculated using
the NMR data. Thus, the degree of substitution was used to determine the
molar mass of the constitutional repeating unit (CRU) and multiplied by
the degree of polymerization of inulin. Table 1 shows the result of the
obtained data. The values of SEC and NMR are consistent considering Fig. 4. SEM images of spray-dried acetylated inulin particles: (left) particles
suspended in water; (right) particles incubated in water for three days.
that the SEC values refer to polystyrene as standard. The narrow
distribution indicates no sign of acid degradation during the 24 hour
synthesis and purification steps. Propionylated inulin was first spray-dried with the same parameters as the
acetylated inulin using the solvent mixture and 80 °C. The SEM revealed
agglomerated particles which stuck together. Because of this behavior, the
Table 1 – Results of the characterization of inulin and derivatives. spray-drying parameters were adjusted to 40 °C inlet temperature using
Material Tm DS Mw, NMR Mn, SEC PDISEC only acetone as solvent. The produced particles presented a spherical
/ °C / g · mol-1 / g · mol-1 shape, with size ranging from 1 µm to 10 µm.
Inulin 175 0 3300 - -
Ac-Inulin 75 2.4 (80 %) 5400 5600 1.25

Prop-Inulin 45 2.3 (77 %) 6100 6600 1.25

3.2. Spray-drying of inulin and its derivatives

Inulin and modified inulins were processed via spray-drying by using

optimized parameters gained from previous experiments. Therefore we
varied several spray-drying parameters described in the following: the
temperature from 80 °C to 120 °C, the feed rate from 3 mL/min to 6
mL/min, the atomization gas from 360 L/h to 750 L/h and the
Fig. 5. SEM of propionylated inulin particles by spray-drying at (left) 80 °C
concentration from 0.5 % to 5 %. The best parameters were used for the temperature and (right) 40 °C temperature.
encapsulation experiments. For that reason, the closed loop with a
 Colloids and Surfaces A: Physicochem. Eng. Aspects 5

Fig. 6. Release profile of inulin, acetylated inulin and propionylated inulin particles containing 1 % dexpanthenol using a
USP4 flow through cell.

3.3. Release behavior of encapsulated dexpanthenol Table 2 – Results of the encapsulation of dexpanthenol in respect of yield
and encapsulation efficiency.
In the next step, dexpanthenol was encapsulated in inulin, Ac-In and Prop- Material mPolymer mDexpanthenol Yield Encapsulation
In using the spray-drying process. The yields of the experiments were / mg / mg /% efficiency / %
found to be between 60 % and 82 % (see table 2). Inulin 990 10 78 96
The content of dexpanthenol was 1 % of the matrix material. The particles
Ac-Inulin 990 10 82 100
showed high encapsulation efficiency around 100 %. In Fig. 6 the result
Prop-Inulin 990 10 60 100
of the release experiment is shown.

Figure 7. SEM images of encapsulated dexpanthenol in inulin particles as matrix in different states: powder (A);
suspended in water (B) and acetylated inulin as powder (C); suspended in water (D).
6 Colloids and Surfaces A: Physicochem. Eng. Aspects

[4] Umer, H.; Nigam, H.; Tamboli, A. M.; Nainar, M. S. M.

Prior analyzed inulin particles showed a burst release behavior, due to the Microencapsulation: Process, Techniques and Applications International
solubility and swelling properties in aqueous solutions. In contrast, the Journal of Research in Pharmaceutical and Biomedical Sciences 2011, 2,
modified inulin derivatives Ac-In and Prop-In revealed a longer release 474.
profile. [5] Kaspar, O.; Jakubec, M.; Stepanek, F. Characterization of spray dried
In order to compare the particles before and after the incubation in water, chitosan-TPP microparticles formed by two- and three-fluid nozzles
SEM images were taken to explain the release behavior. Fig. 7 shows Powder Technol. 2013, 240, 31.
inulin and Ac-In particles in the dry state (A and C) and the particles after [6] Tokarova, V.; Kaspar, O.; Knejzlik, Z.; Ulbrich, P.; Stepanek, F.
incubation in water for 5 minutes (B and D). As expected, inulin showed a
Development of spray-dried chitosan microcarriers for nanoparticle
difference in shape and surface of the particles. After a few minutes in
delivery Powder Technology 2013, 235, 797.
contact with water, the particle surface presented tears and the particles
[7] Elzoghby, A. O.; Samy, W. M.; Elgindy, N. A. Novel Spray-Dried
agglomerated.
Genipin-Crosslinked Casein Nanoparticles for Prolonged Release of
Due to the larger surface area, the diffusion process is accelerated, leading
Alfuzosin Hydrochloride Pharmaceutical Research 2013, 30, 512.
to the burst release of the drug. In comparison, the Ac-In particles
[8] Kolakovic, R.; Laaksonen, T.; Peltonen, L.; Laukkanen, A.; Hirvonen,
revealed no difference in size or shape, which leads to the conclusion that
the modifications stabilize the particles in aqueous solutions and prevent a J. Spray-dried nanofibrillar cellulose microparticles for sustained drug
burst release. After 24 h a release of 60 % dexpanthenol was detected. The release International Journal of Pharmaceutics 2012, 430, 47.
remaining dexpanthenol could be released after degradation or further [9] Oliveira, W. P.; Rattes, A. L. R. Spray drying conditions and
swelling after long incubation period. encapsulating composition effects on formation and properties of sodium
Propionylated inulin only released 10 % of the encapsulated dexpanthenol diclofenac microparticles Powder Technology 2007, 171, 7.
after 24 h. This can be explained by the hydrophobicity of the particle [10] Stefanescu, E. A.; Stefanescu, C.; Negulescu, I. I. Biodegradable
surface due to the modification with propionic anhydride. The propionate Polymeric Capsules Obtained via Room Temperature Spray Drying:
ester is more hydrophobic when compared to the acetate group. By having Preparation and Characterization Journal of Biomaterials Applications
such a high degree of substitution, the amount of remaining hydroxyl 2011, 25, 825.
groups is too weak to interact with water causing the particles to swell. [11] Hede, P. D.; Bach, P.; Jensen, A. D. Two-fluid spray atomisation and
For Prop-In a long term release is expected, which was driven by pneumatic nozzles for fluid bed coating/agglomeration purposes: A
diffusion of dexpanthenol through the outer layer. review Chemical Engineering Science 2008, 63, 3821.
[12] Poulain, N.; Dez, I.; Perrio, C.; Lasne, M. C.; Prud'homme, M. P.;
4. Conclusion Nakache, E. Microspheres based on inulin for the controlled release of
serine protease inhibitors: preparation, characterization and in vitro
The purpose of this study was an investigation of the side-chain release Journal of Controlled Release 2003, 92, 27.
modification according to the release profile. Syntheses of acetylated and [13] Beirao-da-Costa, S.; Duarte, C.; Bourbon, A. I.; Pinheiro, A. C.;
propionylated inulin were successful and presented a high yield and
Januario, M. I. N.; Vicente, A. A.; Luisa Beirao-da-Costa, M.; Delgadillo,
degree of substitution. The materials were processed via spray-drying and
I. Inulin potential for encapsulation and controlled delivery of Oregano
dexpanthenol could be encapsulated. The investigation of the release
essential oil Food Hydrocolloids 2013, 33, 199.
behavior showed a prolonged release of dexpanthenol with acetylated
[14] Wu, X. Y.; Lee, P. I. Preparation and characterization of inulin ester
inulin and propionylated inulin particles compared to native inulin.
microspheres as drug carriers Journal of Applied Polymer Science 2000,
77, 833.
Acknowledgements
[15] Mensink, M. A.; Frijlink, H. W.; Maarschalk, K. V.; Hinrichs, W. L.
We thank the Georg Breuer GmbH for the donation of the inulin. The J. Inulin, a flexible oligosaccharide I: Review of its physicochemical
SEM images were performed by Monika Riedl (Fraunhofer IGB). We characteristics Carbohydrate Polymers 2015, 130, 405.
would like to thank the Konrad-Adenauer-Foundation for financial [16] Jain, A. K.; Sood, V.; Bora, M.; Vasita, R.; Katti, D. S.
support. Electrosprayed inulin microparticles for microbiota triggered targeting of
colon Carbohydrate Polymers 2014, 112, 225.
References [17] Vehring, R. Pharmaceutical particle engineering via spray drying
Pharmaceutical Research 2008, 25, 999.
[1] Wang, A. Z.; Langer, R.; Farokhzad, O. C. Nanoparticle Delivery of
Cancer Drugs In Annual Review of Medicine, Vol 63; Caskey, C. T.,
Austin, C. P., Hoxie, J. A., Eds.; Annual Reviews: Palo Alto, 2012; Vol.
63, p 185.
[2] Sinha, V. R.; Trehan, A. Biodegradable microspheres for protein
delivery Journal of Controlled Release 2003, 90, 261.
[3] Reis, C. P.; Neufeld, R. J.; Ribeiro, P. A. J.; Veiga, F.
Nanoencapsulation I. Methods for preparation of drug-loaded polymeric
nanoparticles Nanomed. Nanotechnol. Biol. Med. 2006, 2, 8.
 Colloids and Surfaces A: Physicochem. Eng. Aspects 7

Graphical Abstract

Highlights

 Modification of inulin with acid anhydrides shows high degree of substitution

 Spray-drying of modified inulin needs optimized process parameters
 Release of encapsulated drug can be adjusted by the modification of inulin