pH Sensitive Interpenetrating Network Microgels of
Sodium Alginate-Acrylic Acid for the Controlled Release
of Ibuprofen
V. Ramesh Babu, K. S. V. Krishna Rao, M. Sairam, B. Vijaya Kumar Naidu,
Kallappa M. Hosamani, Tejraj M. Aminabhavi
Drug Delivery Division, Center of Excellence in Polymer Science, Karnatak University, Dharwad 580003, India
Received 15 April 2005; accepted 26 July 2005
DOI 10.1002/app.22760
Published online 19 December 2005 in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: pH-Sensitive interpenetrating network (IPN)
microgels (MGs) of sodium alginate (NaAlg) and acrylic
acid have been prepared by using water-in-oil (W/O) emul-
sion technique. The MGs were characterized by Fourier
transform infrared spectroscopy (FTIR), differential scan-
ning calorimetry (DSC), X-ray diffractometer (X-RD). The
release of ibuprofen (IB), an anti-inflammatory drug, from
these MGs was studied in pH 1.2 and 7.4 media. MG net-
work consists of NaAlg, which disintegrates in the intestinal
fluid, while poly(acrylic acid) provides pH-sensitivity to the
microgel network. The system developed in this study
showed a pH-sensitivity for the release of IB, which was
attributed to the diffusion controlled release of the drug
through the surfaces of MGs that undergo disintegration
after swelling, depending upon the chemical composition of
MGs and pH of the medium. © 2005 Wiley Periodicals, Inc.
J Appl Polym Sci 99: 2671–2678, 2006
Key words: sodium alginate; acrylic acid; IPNs; drug deliv-
ery
INTRODUCTION
Biodegradable polymers have been extensively used
to develop controlled release (CR) formulations
1–3
to
decrease the release rates of the drugs having short
plasma life. Among the various polymers employed,
hydrophilic biopolymers are quite suitable in oral ap-
plications
4
due to their inherent advantages over the
synthetic polymers. Sodium alginate (NaAlg), a natu-
ral polysaccharide, composed of d-mannuronic acid
and d-guluronic acid is derived from brown sea-
weeds. This polysaccharide has been used extensively
in food industry as a gelling agent and for encapsula-
tion of living cells.
5–7
NaAlg is a biodegradable poly-
mer that has been used in drug delivery applica-
tions.
8 –10
Earlier literature cites many applications of
NaAlg in agriculture
11–13
after when it is crosslinked
with glutaraldehyde. From a search of the literature,
we find no studies on the use of NaAlg and acrylic
acid for the CR of nonsteroidal anti-inflammatory
(NASID) drugs. This prompted us to undertake a de-
tailed study on the CR of ibuprofen (IB), a water
insoluble drug. Pure IB is a nonsteroidal anti-inflam-
matory drug used extensively in the treatment of var-
ious musculo-skeletal disorders and painful condi-
tions. The drug has proven its therapeutic efficacy,
tolerability, and safety in the treatment of rheumatoid
arthritis, osteoarthritis, and ankylosing spondylitis for
the quick relief of pain.
14
However, its short plasma
half-life of 1–3 h following oral dosing
15
necessitates
frequent administration to maintain the desired con-
stant levels. IB can be readily absorbed throughout the
gastro-intestinal tract and can be eliminated rapidly
after administration. In this research, we have devel-
oped the CR, formulations of IB with NaAlg and
acrylic acid. Earlier, CR of antihypertensive drugs
through the tableted microspheres of cellulose deriv-
atives have been reported.
16 –18
In continuation of our
ongoing program of research,
19,16
we report here the
in vitro CR data for IB through the interpenetrating
network (IPN) of microgels (MGs) prepared from
NaAlg and acrylic acid in different compositions. Ef-
fect of acrylic acid content, crosslinking agent, and
drug concentration on the release rates of IB has been
investigated.
EXPERIMENTAL
Materials and methods
Acrylic acid, sodium alginate (low viscosity), potas-
sium persulfate, light paraffin oil, and glutaraldehyde
(25% aqueous solution; GA) were purchased from s.d.
Fine Chemicals, Mumbai, India. Tween-80 was pur-
chased from Sigma Chemical Co. Ibuprofen (purity
Correspondence to: T. M. Aminabhavi (aminabhavi@yahoo.
com).
Journal of Applied Polymer Science, Vol. 99, 2671–2678 (2006)
© 2005 Wiley Periodicals, Inc.