@conference{
author = "Ćirić, Ana and Đekić, Ljiljana",
year = "2020",
abstract = "Introduction
Ibuprofen (IBU) is commonly used non-steroidal
anti-inflammatory drug. It is a weak acid (pKa ~4.5)
with low pH dependent aqueous solubility (46
μg/mL at pH 1.5 and ˃300 μg/mL at pH˃7, at 25
°C). The most commonly used oral dose is 200–600
mg/6h. Drug solubility, which affects the dissolution
and absorption from the formulation is a common
problem in developing efficient formulation for oral
IBU delivery (Ćirić et al., 2020; Irvine et al., 2018).
Chitosan (CH) and xanthan gum (XG)
polyelectrolyte complexes (PECs) already
demonstrated improved drug solubility,
permeability, pH sensitivity and controlled drug
release. Polycationic CH can interact
electrostatically with negatively charged compounds
(Sogias et al., 2012), such as XG, for the
development of PEC-based drug carriers.
IBU encapsulation procedure could influence the
drug-polymer interactions and the PECs formation.
The aim of this study was to evaluate the influence
of IBU encapsulation procedure on the formation
and properties of CH/XG PECs as drug carriers.
Materials and methods
Three different procedures of IBU (BASF,
Germany) encapsulation were performed. In the
procedure A, IBU was mixed with formed PEC
hydrogel consisting of medium molecular weight
CH (Sigma Aldrich, USA) and XG (Jungbunzlauer,
Switzerland) (4.6A). In the procedure B, IBU was
dispersed in the XG solution before mixing with the
CH solution and PEC formation (4.6B). In the
procedure C, IBU was added into the aqueous
medium after the complexing of CH and XG and
allowed to diffuse into the PEC (4.6C). The
concentration of both polymers in the aqueous
solutions was 0.65% w/v, and their volume ratio 1:1.
The pH of CH solutions was adjusted to 4.6 with
acetic acid. Mixing was performed on laboratory
propeller mixer RZR 2020 (Heidolph, Germany).
IBU-to-polymers mass ratio was 1:1.
The evaluation of PECs formation and the
strength of interactions between the polymers and
IBU was done by pH (HI 9321, Hanna Instruments,
USA), conductivity (CDM 230, Radiometer,
Denmark) and rheological measurements (Rheolab
MC 120, Paar Physica, Austria) by increasing the
shear rate from 0 to 100 s-1 and back to 0 s-1 at
20±0.2 °C, in triplicate.
PEC hydrogels were dried under ambient
conditions, grinded and sieved. Then, the yield
(%Y), the IBU encapsulation efficiency (%EE) and
the drug loading (%DL) were calculated. The total
amount of CH, XG and IBU, the initial amount of
IBU used for PEC preparation and the IBU/polymers ratio were considered 100% for %Y, %EE and
%DL, respectively. The calculation of %EE and
%DL: 20 mg of each PEC was dissolved in 100 ml
of methanol/phosphate buffer pH 7.2 (80:20 V/V) by
sonication (Sonorex RK1024, Bandelin, Germany).
IBU concentration was determined
spectrophotometrically at 224 nm (Evolution 300,
Thermo Scientific, USA).
Results and discussion
After the complexing of CH and XG and the
encapsulation of IBU, the pH values of 4.33±0.05
for 4.6A, 4.49±0.05 for 4.6B and 4.11±0.03 for 4.6C
were measured. The lowest pH of 4.6C can be
explained by the diffusion of hydrogen ions into the
hydrogel from the PEC preparation medium, due to
IBU dissociation. The highest pH for 4.6B could be
explained by the dispersion of IBU in XG solution at
high drug concentration. That suppresses its
dissociation, resulting in lower concentrations of
hydrogen ions into the hydrogel. The ionization
ability of IBU, responsible for its non-covalent
interactions with CH and XG, may accelerate the
dissolution of this crystalline drug by partial
disruption of its crystal lattice, which could
potentially influence the release kinetics of IBU
from PEC-based carriers (Sogias et al., 2012).
The conductivity decreased during the formation
of PECs, confirming the establishment of
interactions between the polymers and IBU. The
final conductivity of 4.6A was 920±11 μS/cm, of
4.6B was 615±3 μS/cm, and of 4.6C 833±67 μS/cm.
The differences between the samples were expected
since only free ions are responsible for the
conductivity of samples (Ćirić et al., 2020).
All PECs showed pseudoplastic flow behavior
with thixotropy. Thixotropy was evaluated based on
the hysteresis area (H) values. The highest value of
1019.10±297.01 Pa/s was detected for 4.6B, while
the lowest, 68.20±47.39 Pa/s, was measured for
4.6A. The H of 4.6C was 784.06±143.63 Pa/s.
Higher H values are correlated with stronger
interactions between IBU and polymers (Ćirić et al.,
2020; Djekic et al., 2016). The strength of the
interactions was also evaluated by measuring the
apparent viscosity (maximal at 11.1 s-1 – ηmax, and
minimal at 100 s-1 – ηmin) of PECs. The highest ηmax
was measured for 4.6B (4.97±0.43 Pa·s), and the
lowest for 4.6A (3.92±0.36 Pa·s). The ηmax for 4.6C
was 4.30±0.23 Pa·s. The ηmin for all samples was
0.64±0.08 Pa· s. These results are in accordance both
with thixotropy and the conductivity of the samples.
The highest %Y and %EE had 4.6B
(54.14±3.14% and 59.05±3.14%, respectively), and
the lowest 4.6C (18.70±4.23% and 0.89±0.05%,
respectively). For 4.6A, %Y was 48.04±2.08%, and
%EE 53.19±3.07%. %DL ~50% for 4.6A and 4.6B
and ~2.5% for 4.6C indicated that the PEC 4.6B
resulted in the best characteristics as a carrier of
poorly soluble, highly dosed drug, such as IBU.
Conclusion
IBU encapsulation by dispersion in the XG
solution before mixing with the CH solution (PEC
formation) could be considered optimal to prepare
PECs as promising drug carriers with strongest
interpolymer interactions, the highest %Y, and %EE.",
publisher = "Macedonian Pharmaceutical Association, Faculty of Pharmacy, Ss Cyril and Methodius University in Skopje",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Characterization of chitosan/xanthan gum polyelectrolyte complexes as carriers for ibuprofen: influence of drug encapsulation procedure on complex formation",
volume = "66",
number = "Suppl 1",
pages = "103-104",
doi = "10.33320/maced.pharm.bull.2020.66.03.051"
}
