Original Article




Available online at
www.heca-analitika.com/hjas

Heca Journal of Applied Sciences

Vol. 1, No. 1, 2023

DOI : 10.60084/hjas.v1i1.10 Page | 19

Optimization of Starch—κ-Carrageenan Film as Drug Delivery System
Using Response Surface Method
Khairun Nisah
1
, Afrilia Fahrina
2
, Diva Rayyan Rizki
3
and Kana Puspita
4,*

1
Department of Chemistry, Faculty of Sciences and Technology, Universitas Ar-Raniry, Banda Aceh 23111, Indonesia;
[email protected] (K.N.)
2
Research Center for Marine and Land Bioindustry, National Research and Innovation Agency (BRIN), North Lombok 83756, Indonesia;
[email protected] (A.F.)
3
Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, 23111, Indonesia; [email protected] (D.R.R.)
4
Department of Chemistry Education, Faculty of Teacher Training and Education, Banda Aceh 23111, Indonesia;
[email protected] (K.P.)

* Correspondence: [email protected]

Article History

Received 27 April 2023
Revised 23 May 2023
Accepted 4 June 2023
Available Online 10 June 2023

Keywords:
Biopolymer
Central composite design
Design expert
FT-IR
Polyelectrolyte complex
Abstract

Development of drug delivery systems (DDS) has been widely carried out using safe
biopolymers – starch and κ-carrageenan. However, for optimal use, the foregoing
polymers still suffers from mechanical weakness. Combining both polymers could
enhance the properties of each of the polymer. This research aimed of improving the
applicability of starch and κ-carrageenan as DDS by means of polyelectrolyte
complexation to form a polymer film. The composition ratio of starch:κ-carrageenan was
optimized using response surface method (RSM) on Design Expert 11.0 based on water
swelling, tensile strength, and disintegration time of the film. Fourier transform infrared
spectrometry was performed on the prepared starch—κ-carrageenan film and suggested
the successful film preparation. The bulk characteristics of the film are dependent on the
starch or κ-carrageenan composition ratio, where starch has been associated with higher
thickness, while κ-carrageenan — rigidity. From the RSM, the optimized composition was
revealed to be 2.95 and 2.84 g for starch and κ-carrageenan, respectively, in a 60 mL
aqueous solvent. The predicted optimum properties of the film were 160.21%, 3.26 MPa,
and 17.47 min for swelling degree, tensile strength, and disintegration time, respectively.
Taken altogether, the characteristics of starch or κ-carrageenan individually could be
modified by polymeric combination, where they could be optimized by means of RSM.


Copyright: © 2023 by the authors. This is an open-access article distributed under the
terms of the Creative Commons Attribution-NonCommercial 4.0 International License.
(https://creativecommons.org/licenses/by-nc/4.0/)
1. Introduction
Starch and κ-carrageenan have been widely used in the
field of biomedicine because of their abundance, non-
toxicity, and biocompatible [1]. In addition, starch can be
digested in human body, making it a good drug delivery
system (DDS) [1]. However, starch alone has major
drawbacks of being mechanically weak a nd easily
dissolvable in water. Moreover, starch could attract free
water molecules from the air and subsequently reduced
the material’s durability. To overcome, polymer
combination has been evidenced to improve the native
properties of starch [2, 3]. Even among our research
group, we have employed the same strategy and
successfully improved the physical and chemical
properties of cellulose [4–6], chitosan [7–9], and pectin
[10, 11].

Heca Journal of Applied Sciences, Vol 1, No 1, 2023
Page | 20

In this study, the polymer blend consists of starch and κ-
carrageenan. Similar to starch that is abundant in plants,
plenty number of κ-carrageenan is produced by edible
seaweed. This biopolymer has been commonly used as a
stabilizer and thickener in food industries. Its application
as DDS has been well recognized among researchers
owing to its possession of sulfate ester functional group
that has a strong affinity with drugs. Moreover, this
functional group is responsible for the gelling property
and dissolubility of κ-carrageenan which are significant
parameters in DDS. However, the functional group is also
responsible for the adverse health effects of being
cytotoxic (note that κ-carrageenan is generally safe but in
some of its forms, cytotoxicity may be increased,
especially due to the sulfate group), anti-coagulant, and
pro-inflammatory [12]. Since the functional group is
negatively charged, it could form a polyelectrolyte
complex with cationic starch when dissolved in water [13,
14]. The combination could enhance the mechanical
strength as well as reduce the toxicity of κ-carrageenan
[13, 15]. Hence, combining the two polymers in this
present study is also meant to improve κ-carrageenan
beneficial properties as DDS.
2. Materials and Methods
2.1 Materials
Biopolymers used in this study, starch and κ -
carrageenan, are purchased from the local store in food
grade quality (Banda Aceh, Indonesia). Other chemicals
included sodium tripolyphosphate and glycerol which
were purchased from Merck (Selangor, Malaysia) in
analytical grade quality. All materials used in this
research without any further purification.
2.2 Preparation of starch—κ-carrageenan films
Inversion method was used to construct the film with
starch:κ-carrageenan ratios of 1:1, 1:2, 2:1, 2:3, and 3:2
w/w. Both polymers in powder form were dissolved in 60
mL distilled water, followed by the addition of sodium
tripolyphosphate (2%) and glycerol (96%) and stirred for
2 h (80 °C; 120 rpm). Casting solution was then poured
onto acrylic molds and left-cold for 24 h at room
temperature before ready for use.
2.3 Characterization
Identification of functional group was carried out by
Fourier transform infrared (FT-IR) spectrometry on FT-IR
Cary 630 Anti Agilent (Penang, Malaysia). Prior to FT-IR
analysis, the sample was oven-dried at 40 °C overnight
and crushed into powder. Swelling degree was measured
using distilled water and performed at room
temperature. Time to disintegrate was based on
disintegration test protocol using distilled water (at room
temperature). Tensile strength value was obtained from
Universal Testing Machine HT8503 (Hung Ta Instrument
Co., Ltd, Taichung, Taiwan) following ASTM D638-TYPE IV.
All measurements were carried out in triplicate.
2.4 Optimization using response surface method
The composition of the polymeric film was optimized
based on water swelling (Y1), tensile strength (Y2), and
disintegration time (Y3). Y1 and Y2 act as maximizing
functions, while Y3 – minimizing function. Independent
variables were starch composition (X1) and κ -
carrageenan (X2) with a constrain limit of 0—3. The
parameters were input into Design Expert 11.0 to run the
response surface method (RSM) with central composite
design (CCD) approach.
2.5 Statistical analysis
Data from the CCD model was calculated for their
average, median, and standard deviation (Std dev).
Statistical significance was based on ANOVA. R-square
was used to determine the data agreement in the model.
All statistical data were generated from Design Expert
11.0.
3. Results and Discussions
3.1 Characteristics
Bulk characteristics and visual appearances of the films
have been presented in Table 1. Addition of starch appear
to give more thickness and roughness to the film, while
addition of κ-carrageenan – more rigidity. Therefore,
Table 1. Bulk characteristics and visual appearances of starch—
κ-carrageenan film.
Bulk characteristics Visualization
Starch: κ-
carrageenan
ratio (w/w)
Very thin, elastic,
smooth, and
homogenous

1:1
Smooth, homogenous,
thin, and elastic

2:1
A little rough, thin, less
homogenous, and elastic

1:2
Homogenous, strong,
thick, rough, and rigid

3:2
Not homogenous, thick,
strong, rough, and very
rigid

2:3

Heca Journal of Applied Sciences, Vol 1, No 1, 2023
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Figure 1. FT-IR spectra of starch, κ-carrageenan, and starch—κ-carrageenan film.

by varying composition, we can control the bulk
characteristics of the film.
The functional groups characteristics of the tested
polymers could be observed through FT -IR spectral
profile presented in Figure 1. Both polymers are
polysaccharides and show identical FT-IR spectral
profiles. A narrow band at around 1000 cm-1 is typical for
carbohydrates which are originated from the carbonyl
vibration. The distinctive FT-IR characteristic which can be
observed only in κ-carrageenan is a spectral peak at 1212
cm
-1
which is assigned as S=O vibration. Its presence in
starch—κ-carrageenan suggests the success of the
polymer preparation.
Quantitative properties of the starch—κ-carrageenan
film with different composition ratio have been
presented in Table 2. The greatest water swelling was
observed in composition where starch had dominant
composition. Meanwhile, the highest mechanical
strength was obtained from a sample consisting of 3:2
starch:κ-carrageenan. Sample with the highest durability
against disintegration test is assigned to that with a ratio
of 1:2 (starch:κ-carrageenan).
3.2 CCD-based optimization results
All response variables were matched with the first order
model, second order model, and square models. For Y1
and Y2, the most representative model was the quadratic
model. Meanwhile, for Y3, the best model is the linear
one. The regression (R
2
) shows that Y1 and Y2 have the
acceptable fitness to the model (R
2
=0.963 and 0.993,
respectively), while the contrary result was

Table 2. Swelling degree, tensile strength, and disintegration
time of starch—κ-carrageenan film.
Ratio Water
swelling (%)
Tensile
strength ((MPa)
Disintegration
time (min)
1 : 1 72.0 0.33 5.8
1 : 2 102 0.36 17.34
2 : 1 113.7 0.70 10.11
2 : 3 85.9 1.61 13.7
3 : 2 158.1 2.90 12.16
obtained for Y3 (R
2
=0.719). Based on ANOVA, all response
variables are statistically significant (p<0.005), hence their
applicability as variable in the model. Based on the
model, we obtained the following mathematical
relationship:
Y1 = – 26.78 X1
2 – 46.52 X2
2 + 50.71 X1X2 + 77.60
X1 + 44.63 X2 – 8.18
(1)
Y2 = 0.2546 X1
2 – 0.0911 X2
2 + 0.3216 X1X2 –
0.4192 X1 + 0.00971 X2 + 0.0484
(2)
Y3 = 1.92X1 + 4.61 X2 – 1.29 (3)

Positive values of factors from the polynomial or linear
equations above indicate the response synergism, whilst
the negative sign represents antagonism. Results from
the response surface post analysis with confidence of
95% confirm the optimum composition for starch (X1)
and κ-carrageenan (X2) which are 2.95 and 2.84 g,
respectively. If the compositions were used to prepare
the starch—κ-carrageenan hybrid film, the predicted
composition would be as presented in Table 3. From the
predicted averages or medians, water swelling, tensile
strength, and disintegration time appeared to reach
160.21%, 3.26 MPa, and 17.47 min, respectively. For

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Figure 3. Desirability and optimization results for response variables water swelling (Y1), tensile strength (Y2), and disintegration time
(Y3). Increasing intensity from blue to red indicate the optimized ratio.
better presentation, the desirability and optimization
results have been presented in Figure 3. It shows that the
optimization could provide improved properties of either
starch or κ-carrageenan in the film. These overall findings
are in line with previously reported studies [13, 14].
Nonetheless, as the limitation of this study, a validation
has not been performed on the actual value.
Table 3. Predicted values of swelling degree, tensile strength,
and disintegration time of the starch—κ-carrageenan film,
Response Average Median Std dev
Water swelling (%) 160.206 160.206 19.0677
Tensile strength
(MPa)
3.25599 3.25599 0.134657
Disintegration time
(min)
17.4665 17.4665 4.23702

4. Conclusions
Polymer combination could enhance the properties of
starch and κ-carrageenan as DDS. Optimization using
RSM revealed that starch:κ-carrageenan ratio of 2.95:2.84
w/w as the optimum composition with predicted median
swelling degree, tensile strength, and disintegration time
of 160.21%, 3.26 MPa, and 17.47 min, respectively.
Further investigation is required, especially for the
validation.
Author Contributions: Conceptualization, K.N. and A.F.;
methodology, K.N. and A.F.; software, A.F.; validation, D.R.R. and
K.P.; formal analysis, K.P.; investigation, K.N. and A.F.; resources,
K.N.; data curation, A.F.; writing—original draft preparation, K.N.
and A.F.; writing—review and editing, D.R.R. and K.P.;
visualization, A.F.; supervision, K.N. All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.

Heca Journal of Applied Sciences, Vol 1, No 1, 2023
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Ethical Clearance: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data are available upon
reasonable request to the corresponding author.
Acknowledgments: Authors wished to thank the students from
Department of Chemistry, Faculty of Sciences and Technology,
Universitas Ar-Raniry who acted as research assistant in this
project.
Conflicts of Interest: The authors declare no conflicts of
interests.
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