final .cdr

®
U.V. Bhosale et al Preparation and In Vitro Evaluation of Acyclovir Loaded Eudragit RLPO Nanoparticles as Sustained Release Carriers
effect means that increasing the concentration causes the
emulsion to be more stable, hence leading to smaller
[20]
particles .
From Fig.2 and Table 1, it is revealed that as drug : polymer
®
(acyclovir: Eudragit RLPO)
ratio increased from 1:1.5 to 1:2
particle size increased significantly and drug entrapment
also increased but thereafter, further increase in
drug:polymer ratio showed reduced or insignificant change
in the drug entrapment efficiency .
This can be explained by observing drug entrapment
efficiency of factorial formulations F3, F6, F9 where drug:
polymer ratio increased from 1:1.5 to 1:2 and 1:2.5
respectively with constant concentration of stabilizer
( Pluronic F68) i.e. 0.25%. Drug entrapment efficiency
increased from 72.4% to 78.5% and then decreased to 68.7
%. It is also observed that as percentage of stabilizer
increased from 0.25% to 1%, entrapment efficiency and
particle size decreased significantly, the same can be
explained with respect to factorial formulations F1, F4, F7
and F2, F5, F8 where it is observed that as drug: polymer
ratio increases, entrapment efficiency increased significantly
but further increases in drug: polymer ratio has negative or
insignificant effect on drug entrapment. For factorial
formulations F1, F2, F3 where drug:polymer ratio is
constant i.e. 1:2.5 and concentration of stabilizer decreased
from 0.75 % to 0.25%, drug entrapment efficiency increased
from 56.2% to 72.4% and particle size increased from 410
nm to 743 nm. Thus it can be concluded that the surfactant
had greater influence on both dependent parameters
(particle size and drug entrapment) as compared to drug:
polymer ratio.
Drug release from nanoparticles and subsequent
biodegradation are important for developing successful
formulations. The release rate of nanoparticles depends
upon i) desorption of the surface-bound/adsorbed drug ; ii)
diffusion through the nanopaticle matrix; iii) diffusion (in
case of nanocapsules) through the polymer wall; iv)
nanoparticle matrix erosion: and v) a combined
erosion/diffusion process. Thus, diffusion and
[21]
biodegradation govern the process of drug release .
It is proposed that there are two main pathways of drug
release from swellable nanoparticles. First, there is a rapid
release of drug from the nanoparticles, which could stem
from drug adsorbed on the nanoparticle surface. Then a
slower, more controlled release takes place, which is possibly
related to nanoparticle diffusion of the drug through the
[22]
nanoparticle shell .
89
The mechanism of drug release from nanoparticles is
determined by different physical-chemical phenomena. The
exponent 'n' has been proposed as indicative of the release
mechanism. In this context, n = 0.43 indicates Fickian
release, n = 0.85 indicates a purely relaxation (Case II) and
> 0.85 indicates super case II controlled delivery.
Intermediate values 0.43 < n < 0.85 indicate an anomalous
behavior (non-Fickian kinetics) corresponding to coupled
[23]
diffusion/polymer relaxation .
The average percentage release was fitted into different
release models: zero order, first order and Higuchi's square
root plot. The models giving a correlation coefficient close to
unity were taken as the order of release In vitro drug release
data of all selected factorial formulations was subjected to
goodness of fit test by linear regression analysis according to
zero order and first order kinetic equations, Higuchi's, and
Korsmeyer-Peppas models to ascertain the mechanism of
drug release. From various parameters determined for drug
release from nanoparticles based on Peppas model, Higuchi
model and diffusion profile (Table No.2), it is evident that
2
values of 'r ' for Higuchi plots of factorial formulations
ranging from 0.9776 to 0.9934, for first order plots 0.8483 to
0.9940 and those of 'n' (diffusion exponent) values of Peppas
equation from 0.4557 to 0.8701. This data reveals that drug
release follows first order release kinetics with non-Fickian
diffusion mechanism for all factorial formulations except F6,
where drug release follows first order release kinetics with
case II diffusion mechanism. Finally, it can be concluded that
the different drug release rates may be attributed to different
sizes of the nanoparticles. It is expected as the particle size of
®
Eudragit RLPO nanoparticle is smaller, their surface area
will be more and the drug release is faster.
As prepared polymeric nanoparticles has size range in
between 74 nm to 566 nm, for these colloidal carriers sites
for uptake are expected as Peyer's patches (PP) and
lymphoepithelial M cell. It has been shown that larger
nanoparticles remain in the Peyer's patches, whereas
nanoparticles with lower particle size range disseminate
[10]
systemically .
Development of Polynomial Equations:
From the data of experimental design and parameters
(Table No.1) for factorial formulations F1 to F9, polynomial
equations for two dependent variables (particle size and %
drug entrapment) have been derived using PCPDisso
2000V3 software.
The equation derived for particle size is:
RJPS, Apr-Jun, 2011/ Vol 1/ Issue 1