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Carbopol gel containing chitosan-egg albumin nanoparticles for
transdermal aceclofenac delivery
Sougata Jana a,∗, Sreejan Manna a, Amit Kumar Nayak b, Kalyan Kumar Sen a,Sanat Kumar Basu a
a Division of Pharmaceutics, Department of Pharmaceutical Tecnology,Kolkata-700032,W.B., Indiab Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj 757086, Odisha, India
a r t i c l e i n f o
Article history:
Received 3 June 2013
Received in revised form
18 September 2013
Accepted 20 September 2013
Available online 30 September 2013
Keywords:
Carbopol 940
Chitosan
Egg albumin
Nanoparticles
Transdermal drug delivery
a b s t r a c t
In the present work, various aceclofenac-loaded chitosan-egg albumin nanoparticles were prepared
through heat coagulation method. These aceclofenac-loaded nanoparticles were characterized by FE-
SEM, FTIR, DSC and P-XRD analyses. The in vitro drug release from nanoparticles showed sustained drug
release over 8 h. Aceclofenac-loaded nanoparticles (prepared using 200 mg chitosan, 500 mg egg albu-
min and 2% (w/v) NaTPP) showed highest drug entrapment (96.32±1.52%), 352.90 nm average particle
diameter and −22.10 mV zeta potential, which was used for further preparation of Carbopol 940 gel for
transdermal application. The prepared gel exhibited sustainedex vivo permeation of aceclofenac over 8 h
through excised mouse skin. The in vivoanti-inflammatoryactivity in carrageenean-inducedratsdemon-
strated comparative higher inhibition of swelling of rat paw edema by the prepared gel compared with
38 S. Jana et al. / Colloids andSurfaces B: Biointerfaces114 (2014) 36–44
Table 1
The composition chart for the preparation of different aceclofenac-loaded chitosan-egg albumin nanoparticles with their drug entrapment efficiencies, average particle
diameters and zeta potentials.
Formulation code Composition Drug entrapment
efficiency (%)
(mean±S.D.; n= 3)
Average particle
diameter (nm)
Zeta potential
(mV)
Chitosan (mg) Egg albumin (mg) NaTPP (% w/v)
F-1 350 350 – 69.37 ± 0.93 553.40 −1.16
F-2 250 450 – 74.30 ± 0.95 501.25 −3.10
F-3 300 400 – 81.26 ± 1.38 489.52 −3.32
F-4 200 500 – 90.54 ± 1.03 446.30 −5.77
F-5 200 500 1 93.68 ± 1.08 388.94 −12.21
F-6 200 500 2 96.32 ± 1.52 352.90 −22.10
2.5. Analysis of in vitro drug release kinetics and mechanism
The in vitro drug release data were evaluated kinetically using
various important mathematical models like zero-order, first-
order, Higuchi, and Korsmeyer–Peppas models [26].
Zero-order model: Q = k0t +Q 0; where Q represents the drug
remaining to be released at time t , and Q 0 is the amount of drug
present in the formulation initially; k0 is the rate constant.
First-order model: Q =Q 0 ek1t ; where Q represents the drug
remaining to be released at time t , and Q 0 is the amount of drugpresent in the formulation initially; k1 is the rate constant.
Higuchi model:Q =kHt 0.5; whereQ represents the drug released
amount per unit area at time t , and kH is the rate constant.
Hixson–Crowell model:Q 1/3 = kt +Q 01/3; whereQ represents the
drugreleasedamountattime t ,andQ 0 isthe amountof drug present
in the formulation initially; k is the rate constant.
Korsmeyer–Peppas model:Q = kt n; whereQ represents the frac-
tion of drug released at time t , k is the rate constant and n is the
diffusional exponent, indicative of drug release mechanism.
Again, The Korsmeyer–Peppas model was employed in the in
vitro drug release behavior analysis of these formulations to dis-
tinguish between competing release mechanisms: Fickian release
Fig. 6. (a) The comparative ex vivo drug permeation from Carbopol 940 gel containing aceclofenac-loaded chitosan-egg albumin nanoparticles and a marketed aceclofenac
gel through excised mouse skin (mean±S.D.; n = 3); (b) comparative percentage inhibition profile of paw edema edema for Carbopol 940 gel containing aceclofenac-loaded
nanoparticles and marketed aceclofenac gel at various time intervals in carrageenan-induced rat model for anti-inflammatory activity evaluation.
min nanoparticles were found 352.90nm and −22.10 mV, respec-
tively. The stabilityand physical conditionof the loaded aceclofenac
within the nanoparticles were confirmed using FE-SEM, FTIR, DSC
and P-XRD analyses. The in vitro drug release from all aceclofenac-
loaded nanoparticles showed sustained drug release over a period
of 8h, which followed Korsmeyer–Peppas model and anoma-
lous (non-Fickian) diffusion mechanism of drug release. Carbopol
940 gel containing 2% (w/v) TPP cross-linked aceclofenac-loaded
chitosan-egg albumin nanoparticles was prepared for transdermal
delivery of aceclofenac. The prepared gel was characterized by pH
and viscosity. The Carbopol 940 gel containing aceclofenac-loaded
nanoparticles showed sustained permeation of aceclofenac over
8 h in ex vivo skin permeation study using excised mouse skin.
However, this Carbopol 940 gel formulation showed faster per-
meation of aceclofenac than that of the marketed aceclofenac gel.
The permeation flux for prepared Carbopol 940 gel was found sig-
nificantly higher ( p< 0.05) (0.0681±0.0008g/cm2/h) than that
of the marketed aceclofenac gel (0.0316±0.0004g/cm2/h). The
in vivo anti-inflammatory activity in male Sprague Dawley rats
using carrageenean-induced rat-paw edema model demonstrated
comparative higher inhibition of swelling of rat paw edema by
Carbopol 940 gel containing aceclofenac-loaded nanoparticles
compared with that of the marketed aceclofenac gel over a period
of 4h. Overall, these results indicated the promise of Carbopol
940 gel containing 2% (w/v) NaTPP cross-linked aceclofenac-loaded
chitosan-egg albumin nanoparticles for transdermal delivery of
aceclofenac with improved permeation profile and thus, improved
patient compliance.
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