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Preparation of Bioblends Using Spray Dryer and

Their Applications in Drug Delivery Systems
ARTICLE in ASIAN JOURNAL OF CHEMISTRY JANUARY 2015
Impact Factor: 0.45 DOI: 10.14233/ajchem.2015.18958

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Asian Journal of Chemistry; Vol. 27, No. 10 (2015), 3734-3738

ASIAN JOURNAL OF CHEMISTRY

http://dx.doi.org/10.14233/ajchem.2015.18958

Preparation of Bioblends Using Spray Dryer and their Applications in Drug Delivery Systems
E. OZSAGIROGLU*, E.N. HAYTA and Y. AVCIBASI GUVENILIR
Chemical Engineering Department, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey
*Corresponding author: Fax: +90 212 2853425; Tel: +90 212 2857370; E-mail: ozsagiroglu@itu.edu.tr
Received: 26 December 2014;

Accepted: 21 January 2015;

Published online: 22 June 2015;

AJC-17336

The importance of the study is to encapsulate L-ascorbic acid in biopolymers in order to obtain (i) enhancing its encapsulation efficiency
(ii) increasing drug release ratio using different pH media. Microspheres based on polycaprolactone, polyethylene glycol and chitosan
biopolymers are prepared by spray drying technique. Another importance of the study is the encapsulation of L-ascorbic acid which is an
essential vitamin for humans. The study includes three different steps. First step is to obtain of low particle size, high surface area and
homogeneous drug encapsulation material using spray dryer. Second part is determination of best efficient drug loading conditions. Final
part of the study is about drug release experiments and calculation of drug release ratio in different pH media. At the end of studies, we
achieved minimum 19.143 0.023 m particle size with 0.897 m2/g surface area, 99.13 % maximum drug loading and 93.18 % drug
release ratio at 2.8 pH medium.
Keywords: Drug delivery systems, Microencapsulation, Drug loading, Drug release, Spray dryer.

INTRODUCTION

Nowadays, pharmaceutical industry has been focused on

some specific biodegradable polymers which are polycaprolactone, polyethylene glycol and chitosan1. These polymers have
many advantages for drug delivery systems. They are biocompatible and biodegradable polymers; polycaprolactone has
porous surface, so drugs can be easily loaded in the polycaprolactone based microspheres. Polyethylene glycol has good
stability and it is able to have temporary hydrogen bonding
with drugs. Chitosan and chitin are the most biocompatible
materials in the world.
Drug encapsulation in colloidal delivery systems is an
efficient approach to improve the pharmacokinetics of
hydrophilic drugs2. These carriers encompass a broad range
of dispersion systems ranging from submicron emulsions to
colloidal particles, such as bio-based polymeric (polycaprolactone,
polyethylene glycol, chitosan, casein and starch) aiming to
protect the drug against degradation, sustain drug release,
increase patient comfort by avoiding repetitive bolus injections
or the use of perfusion pumps and reduce side effects.
Particulate drug carriers can act as delivery vehicles for
drugs through various routes of administration3. On the other
hand, the undesirable adverse effects have to be minimized
and therapeutic improvement has to be maximized at the same
time for an effective and useful drug delivery tool4-7. The only

way to obtain improved therapy is that creating very effective

drug release in the body and bio-based polymers could provide
these vital necessities. Because of these reasons, biodegradable
polymers are preferred for drug delivery systems.
Encapsulation may be defined as a process to entrap one
substance within another substance, thereby producing
particles with diameters of a few nm to a few mm. The substance that is encapsulated may be called the core material, the
active agent, fill, internal phase, or payload phase. The substance that is encapsulating may be called the coating, membrane, shell, carrier material, wall material, external phase, or
matrix. Two main types of encapsulates might be distinguished,
i.e., the reservoir type and the matrix type8. The reservoir type
has a shell around the active agent. This type is also called
capsule, single-core, mono-core or core-shell type. Application
of pressure can lead to breakage of the reservoir type of
encapsulates and thus to the release of its contents. Poly- or
multiple-core type of encapsulates with several reservoir
chambers in one particle also exist. The active agent in the
matrix type is much more dispersed over the carrier material;
it can be in the form of relatively small droplets or more
homogenously distributed over encapsulation. Active agents
in the matrix type of encapsulates are in general also present
at the surface, in contrast to those in the reservoir type9-12.
It is always a fact that performance of a drug delivery
system is about encapsulation and release efficiency. One of

Vol. 27, No. 10 (2015)

Preparation of Bioblends Using Spray Dryer and their Applications in Drug Delivery Systems 3735

the basic requirements for the controlled and balanced release

of the medicament in the body is its ideal spherical shape of
polymeric particles and narrow distribution of their sizes. The
size and shape of the particles play key role in their adhesion
and interaction with the cell11. Another important issue for
drug delivery systems is that stability at outside and sufficient
degradation of drugs inside of human body. To overcome this
problem, blending of biopolymer for drug delivery systems
could be an enormous alternative because biodegradation rate
is easily adjustable by blends of polymers. At these view of
points, preparing of a drug which is easily biodegradable,
biocompatible inside the body and stable outside the body is
the main problem and most important goal for pharmaceutical
industry.
Spray drying is the process of contacting an atomized
stream to be dried with a gas stream that is at a higher temperature than the liquid stream. The higher temperature of the
gas stream causes evaporation of the liquid from the droplets,
forming particles. Recently, the use of this process to manufacture hollow, micron and sub-micron particles has also been
demonstrated12-14. Furthermore, amorphous solid dispersions,
soluble complexes, encapsulated systems, solid self-emulsifying systems and nano-dispersions of poorly soluble drugs
prepared by spray drying are primary solubilization strategies15.
On the basis of these remarks, aim of this work is the
preparation and characterizations of biodegradable and biocompatible polymer based blends and obtain uniform particle
size distribution at the same time. The importance of the study
is production of a stable and effective drug encapsulation
system using ternary polymer mixture by spray dryer. The
main reason of using a ternary polymer mixture is to obtain
the best efficiency of a drug material, because a combination
of these materials can achieve superior characteristics than
each component individually. Another importance of the study
is encapsulation of L-ascorbic acid which is essential vitamin
for humans. For achieving of the goal our study, we use polycaprolactone, polyethylene glycol and chitosan to prepare
drug delivery system and spray dryer was our tool to obtain
microspheres. First of all, we evaluate effects of spray drying
conditions and composition of the microencapsulating
formulation. Secondly, the most uniform distributed particle
sized microsphere is selected and drug is loaded to it. Lascorbic acid is the active ingredient for the study. After that,
drug encapsulation and drug release efficiencies are calculated
and best drying conditions were determined Drug release
experiments are accomplished at different pH values (2.8, 7.4
and 9.6).
EXPERIMENTAL

Polycaprolactone with Mn = 10000 g/mol, Mw = 14000 g/

mol and medium molecular weight chitosan are purchased
from Sigma-Aldrich. PEG-6000 is a gift from Ashland Inc.
L-Ascorbic acid powder (vitamin C) is also obtained from
Sigma-Aldrich. Acetic acid (Merck) and formic acid (Merck)
are used as solvent agents for polymer mixtures and used
without any further purification. Oxalic acid and 2,6-dichloroindophenol sodium salt hydrate are used to determine Lascorbic acid in UV spectrum.

General procedure: Polymer solutions are fed to spray

dryer (Yamato ADL 310 lab scale spray dryer) by a peristaltic
pump and first of all, best drying conditions are determined
by changing drying temperature (120, 135 and 150 C) and feed
flow rate (3, 6 and 9 mL/min). Atomizer pressure is constant
at 1 barg.
Secondly, particle diameter and particle size distribution
are determined and L-ascorbic acid in different weight ratios
are loaded for each microsphere which had the lowest particle
diameter. L-Ascorbic acid loading studies are done by indirect
loading of drug to microspheres at 25 C and 200 rpm.
L-Ascorbic acid contents are 5, 10 and 15 wt %, respectively.
Encapsulation efficiency is calculated by eqn. 112:
Encapsulation efficiency (%) =

Final L - ascorbic acid amounts

100 (1)
Initial L - ascorbic acid amounts

Liquid phase is analyzed by UV at 518 nm to calculate

eqn. 119-22. Drug release calculations are also performed by
UV. 0.5 mg blend/1 mL release medium (pH 2.8, 7.4 and 9.6)
ratio is used. Drug release is calculated by eqn. 28.
Ct
100
(2)
C0
where; Ct refers to drug amount in any time and C0 to drug
amount at t = 0.
Detection method: Polycaprolactone + polyethylene glycol
+ chitosan (PCL + PEG + CH) polymer mixture solutions are
prepared by acetic acid-formic acid solutions with 3:7 (v/v)
ratios. The value of 3:7 (v/v) acetic acid:formic acid is determined by previous studies16-18. Polymer contents in all solutions
are 10 wt % and all ternary polymer mixtures are prepared by
1:1:1 (wt/wt) ratio.
Particle size analyzer (Malvern Mastersizer 2000), Mastersizer is used to obtain particle size diameter with distribution.
Scanning electron microscopy (SEM-Jeol, JSM-6390 LV) is
used to obtain morphological structures of microspheres.
Particle morphology is determined by this way. Thermogravimetric analysis or thermal gravimetric analysis (TGA,
Perkin-Elmer Diamond TG/DTA) is used to analyze blend structure. Ultraviolet Analysis (UV-UV Mini 1240 SHIMADZU)
is used to calculate drug encapsulation efficiency and drug
release ratios.
Drug release (%) =

RESULTS AND DISCUSSION

Yields and particle size distributions with standard

deviation are shown for all studies in Figs. 1 and 2, respectively.
Due to the Fig. 2, Metasizer analyses are done 3 times and
particle diameter distribution is determined by standard
deviation of the results. Final values demonstrate particle size
(m) with standard mean of PCL-PEG-CH microspheres.
Fig. 1 determines that drying efficiency increase by decreasing
of flow rates at 120 C and 135 C; on the contrary drying efficiency increase by increasing of flow rate at 150 C. The reason
of these results is that increasing drying temperature resulted
in agglomeration of polymer mixture, so contact time with
polymer mixture and drying temperature had adversely effect
on diameter distribution19-21. Due to these results, 120 C and 3
mL/min are the best drying conditions because of the lowest
particle diameter with 19.143 0.023 m and highest surface
area with 0.897 m2/g surface area in this study.

3736 Ozsagiroglu et al.

Asian J. Chem.

70

50

80

30
20
10
0

6
Flow rate (mL/min)

40

0
150 C
135 C
120 C

700

PEG

20

900
800

PCL

60

Fig. 1. Yield (wt %) at different drying temperature (C) and flow rates
(mL/min)

300

400
Temperature (C)

600

800

Fig. 4. Thermal gravimetric analysis curve of PCL-PEG-CH microsphere

at 120 C, 3 mL/min

600

100

500

L-ascorbic acid

400

CH
80

300
200
100
0

6
Flow rate (mL/min)

Weight (%)

Particle diameter (m)

CH

40

Weight (%)

Yield (wt%)

100

150 C
135 C
120 C

60

60
PCL
40

Fig. 2. Particle diameter (m) with standard deviations at different drying

temperature (C) and flow rates (mL/min)

SEM micrographs are shown in Fig. 3 for 120 C-3 mL/

min, 135 C-3 mL/min and 150 C-9 mL/min. It is easily seen
that agglomeration increases by increasing of drying temperature. Porous structure of microsphere is also easily shown
in all SEM micrographs. This porous structure is an advantage
because drug loading capacity of porous spheres is higher than
other spherical structures22.
The sample is placed in furnace and burned in the N2
atmosphere without O2 with the ramp 30 C /min up to 800 C.
Thermal gravimetric analysis scan is obtained from the measurement to determine decomposition temperature and char yield.
Thermal gravimetric analysis curves for PCL-PEG-CH bioblend and L-ascorbic acid loaded bio-blend are shown in Figs.
4 and 5, respectively.

(a)

(b)

PEG
20

300

400
Temperature (C)

600

800

Fig. 5. Thermal gravimetric analysis curve of L-ascorbic acid loaded

microsphere

It is seen that TGA curves in Figs. 4 and 5 are blends

because thermal degradation curves goes down step by step.
Fig. 4 illustrates PCL-PEG-CH blend thermal degradation and
it begins about 300 C with chitosan degradation, following
at 350 C with polycaprolactone degradation and finalized at
400 C with PEG-6000 degradation. L-Ascorbic acid (Fig. 5)
shows that the decomposition starts at around 190 C. Four

(c)

Fig. 3. SEM micrographs (a) 120 C, 3 mL/min; (b) 135 C -3 mL/min; (c) 150 C, 9 mL/min

Preparation of Bioblends Using Spray Dryer and their Applications in Drug Delivery Systems 3737

thermal degradation steps are identified and allocated to the

L-ascorbic acid and polymer fractions, respectively, based on
the TGA curves.
Drug release studies are performed under three different
L-ascorbic acid concentrations (5 wt %, 10 wt % and 15 wt %)
with different loading time and PCL-PEG-CH particle
amounts. Microsphere obtained at 120 C and 3 mL/min is
used in drug loading studies because this microsphere had the
lowest particle diameter and also best distributed particles due
to the Metasizer analyses (Figs. 1 and 2). Results are shown in
Figs. 6 and 7 for effects of loading time and effects of particle
amount, respectively.

Loading efficiency (wt%)

100

80

100

80

60

40
pH 2.8
pH 7.4
pH 9.6

20
5 wt % A.A.
10 wt % A.A.
15 wt % A.A.

60

0
0

40

4
Time (h)

Fig. 8. Drug release studies at different release mediums in 8 h

20

2
Time (h)

Fig. 6. Effects of drug loading time for L-ascorbic acid on PCL-PEG-CH

100

Loading efficiency (wt%)

Drug release studies are performed for the most loaded

microsphere obtained in 15 wt % L-ascorbic acid solution by
0.5 mg particle amount. Drug release studies are obtained at
three different release medium by changing pH from 2.8 to
9.6 (Fig. 8).

Loading efficiency (wt%)

Vol. 27, No. 10 (2015)

5 wt % A.A.
10 wt % A.A.
15 wt % A.A.

80

60

40

20

0.5

1.0
1.5
Particle amount (mg/mL)

2.0

Fig. 7. Effects of particle amount for L-ascorbic acid loading on PCL-PEGCH

Drug loading experiments are carried out at 25 C and

200 rpm. Fig. 6 demonstrates that L-ascorbic acid concentrations are rapidly increased in 2 h and stabilized from 2 to
4 h. We achieved significant results in this part and L-ascorbic
acid loading is 99.13 wt % due to UV results.
We also determined the effects of particle amount on drug
loading efficiency by changing particle amounts from 0.5 mg
to 2 mg by increasing of 0.5. Results are showed in Fig. 7. 0.5
mg PCL-PEG-CH in 15 wt % L-ascorbic acid experiment is
the most effective study. We also revealed that increasing
particle amount decreased drug loading efficiency. The
explanation of the result is that increasing particle amount
concluded agglomeration of microspheres, so particle surface
area is decreased and it affected drug loading efficiency in
bad direction.

We achieved peak release points in just 2 h in release

mediums and Fig. 8 also illustrated that decreasing pH
increased drug release efficiency. Drug loaded microspheres
contains PCL-PEG-CH bio-based polymers and particularly
interaction of polycaprolactone and chitosan in acidic medium
is better than higher pH values23. By this way, L-ascorbic acid
release remarkably increased in pH 2.8 (max. 93.18 %) as
shown in the figure above.
Conclusion
In fact the encapsulation efficiency, loading capacity and
drug release behaviour are the most important issues for drug
delivery systems. We suggest an alternative solution to solve
the problems and these are using spray dryer to reduce particle
diameter, to obtain narrow particle size distribution and to
produce blends made by ternary polymer mixture to get best
performance from the encapsulation material.
We achieved the aim of the study by production of a stable
and very effective L-ascorbic acid loaded drug using biodegradable polymer solutions by spray dryer. We also used aqueous
solutions of non-toxic solvents in the study. By these ways,
we succeeded higher drug loading and drug release efficiency
in our study.
Because of unstable and very sensitive L-ascorbic acid,
producing vitamin C drugs are really difficult. However,
another significant result of our study is achieving 93.18 %
L-ascorbic acid release in 2 h.
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