IAJPS 2016, 3 (6), 627-636
Naresh N S and Pratyusha A
CODEN (USA): IAJPBB
ISSN 2349-7750
ISSN: 2349-7750
INDO AMERICAN JOURNAL OF
PHARMACEUTICAL SCIENCES
Available online at: http://www.iajps.com
Research Article
FORMULATION DESIGN AND EVALUATION OF
SAXAGLIPTIN SUSTAINED RELEASE MICROSPHERES
Naresh N S and Pratyusha A
CMR College of Pharmacy, Kandlakoya Village, Medchal Road, Rangareddy District,
Hyderabad, Telangana 501401.
Abstract:
Sustained release oral product namely microspheres for Saxagliptin prepared by Ionotropic gelation technique
to overcome the drug-related adverse effects like gastric irritation, improve its bioavailability in different
gastrointestinal pH conditions. Total nine formulation batches (F1-F6) were formulated using sodium
alginate as drug release modifiers in various proportions and investigate for physicochemical properties and
drug release potential. All investigated properties showed satisfactory results. While increase in the
concentration of sodium alginate dispersions increased sphericity, size distribution, flow properties and mean
diameter of the Microspheres. The drug entrapment efficiency obtained in the range 78.4% to 95.42%. Increase
in the concentration of calcium chloride was significantly affects the mean diameter but no appreciable
change in morphology and drug release behavior. In-vitro study proves that drug release slowly increases
as the pH of the medium is increased. The drug release in batch F1, F2, F3 F4, F5 and F6 containing
sodium alginate. The mechanism drug release from Microspheres was found to be following Higuchi model
graph. From the study it was concluded that controlled release Saxagliptin Microspheres can be developed
successfully by using ionotropic gelation technique.
Key words: Microencapsulation; Ionotropic gelation, Microspheres, Sodium alginate, pH dependent.
Corresponding author:
Naresh N S,
CMR college of pharmacy,
Survey No. 68 & 82,
Road, Rangareddy District,
Hyderabad, Telangana 501401
Mail: [email protected]
Ph; 9603099919
QR code
Please cite this article in press as Naresh and Prathyusha , Formulation Design and Evaluation of
Saxagliptin Sustained Release Microspheres, Indo Am. J. P. Sci, 2016; 3(6).
www.iajps.com
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IAJPS 2016, 3 (6), 627-636
Naresh N S and Pratyusha A
INTRODUCTION:
Microencapsulation is well known method to delay
and modify drug release characteristics. For oral
use, it has been employed to sustain the drug
release and to reduce or eliminate gastrointestinal
tract irritation[1]. It is a process of enclosing
micron size particles of solid or liquid or gases in
an inert shell resulting in the formation of
microparticles or microcapsules or microspheres
[2]. As multiparticulate drug delivery lead to wide
and uniform distribution throughout GIT, a
localized high concentration at a specific point may
be avoided. In addition, multiparticulate delivery
systems spread out more uniformly in the
gastrointestinal tract. This results in more
reproducible drug absorption and reduces local
irritation when compared to single unit dosage
form such as non disintegrating polymeric matrix
tablets [3,4]. Sodium alginate, a natural
polysaccharide which is a mixture of polyuronic
acids composed of residues of d-mannuronic acid
and l-guluronic acid [5]. Alginates have the ability
to form gels by reaction with divalent cations
(Ca2+). The gelation and crosslinking of the
polymers are mainly achieved by exchange of
sodium ions from the guluronic acids with divalent
cations, and the stacking of these guluronic groups
to form the characteristic egg-box structure. The
divalent cations bind to the -L-guluronic acid
blocks in the highly cooperative manner and the
size of the cooperative unit is more than 20
monomers. Each alginate chain dimerizes to form
junctions with many other chains and as the result
gel network are formed [6]. Alginate shrinks at the
low pH and the encapsulated drugs are not
released. In gastric fluid, the hydrated sodium
alginate is converted into porous, insoluble socalled alginic acid skin. Once passed into higher
pH of the intestinal tract, the alginic skin is
converted to soluble viscous layer. This pH
dependent behavior of alginate can be exploited to
customize release profiles [6,7.] To design a new
formulation in the field of pharmaceutical dosage
forms, it is very important to identify the
parameters and variables in the method of
preparation that may affect the properties of the
new dosage form. Statistical design can be used for
analyzing the influence of different factors on the
properties of the system being studied [8].
The objective of the present study was to develop
microspheres of Saxagliptin by Ionotropic Gelation
Technique using hydrophilic carrier to sustain the
release so as to reduce the frequency of dosing and
to improve patient compliance.
MATERIALS AND METHODS:
Saxagliptin From Spectrum lab Hyderabad,
Sodium alginate and Calcium Chloride from
Sd.Fine Chem. Ltd., Mumbai
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Methods
Preformulation Study:
Prior to the development of any dosage form, to
optimize the performance of drug products it is
necessary to have a complete understanding of the
physical and chemical properties of drug substance
by the study of preformulation data.
The development of a new drug substance, as a
dosage forms such as tablet, capsule, suspensions,
etc. we must record some Preformulation data such
as organoleptic characteristics, particle size,
crystallization characteristics, compatibility with
excipient, and also certain techniques like I.R.
analysis,
thin
layer
chromatography,
spectrophotometry, sieving analysis, etc.
Standard Plot for Saxagliptin:
Acid buffer (pH 1.2)
Accurately weighed 200mg of saxagliptin was
dissolved in 10ml of methanol in a 100ml of
volumetric flask and make up the volume with pH
1.2 buffer solution. Take 10ml of this solution
in a 100ml of volumetric flask and make up the
volume with pH 1.2 buffer solution to get working
stock solution having concentration 100g/ml.
From this stock solution aliquots 1ml, 2ml, 3ml,
4ml and 5ml were pipetted out into a series of
50ml volumetric flasks and make up to mark
with pH 1.2 buffer solution in order to get a
concentration within the Beers range from 210g/ml. The absorbance of the resulting solution
was then measured at 243nm using
UV spectrophotometer against respective parent
solvent as a blank. The standard curve was
obtained by plotting absorbance V/s concentration
in g/ml.
Phosphate Buffer (pH 6.8):
Accurately weighed 200mg saxgliptin was
dissolved in 100ml of pH 6.8 phosphate buffer
solution. Take 10ml of this solution in a 100ml of
volumetric flask and make up the volume with
phosphate buffer (pH 6.8) solution to get working
stock-solution having concentration 100g/ml.
From this stock-solution aliquots of 1ml, 2ml, 3ml,
4ml and 5ml were pipetted out into a series of
50ml volumetric flasks and make up to mark with
pH 6.8 phosphate buffer solution in order to get
a concentration within the Beers range from 210 g/ml.
The absorbance of the resulting solution was then
measured at 210nm using UV Spectrophotometer
against respective parent solvent as a blank (i.e. pH
6.8 buffer solution). The standard curve was
obtained by plotting absorbance V/s concentration
in g/ml.
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Naresh N S and Pratyusha A
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Table 1: Formulation design of microspheres
Formulation
Saxagliptin (mg)
F1
F2
F3
F4
F5
F6
200
200
200
200
200
200
Preparation of Microspheres
Microspheres of saxagliptin were prepared by
Ionotropic gelation technique. In the present
work four sets Microspheres were prepared by
using sodium alginate and Calcium chloride as
counter ion. The detailed composition of the
various formulations prepared is as mentioned in
table no.1
Preparation of Sodium alginate Microspheres
In the first set three batches of drug-loaded
Microspheres were prepared (F1, F2, F3). A
solution of sodium alginate (2-4% w/v) was
prepared in 100ml of de ionized water. In 50ml of
sodium alginate solution, weighed quantity
(200mg) of saxglipton was dispersed uniformly.
Bubble free dispersion was dropped through a
syringe into 100ml aqueous calcium chloride
solution and stirred at 100rpm. After stirring for
10minutes, the gelled beads filtration, washed with
0
distilled water, air dried and finely dried at 60 C
for 6 h in a oven.
In second set microspheres were prepared (F4,F5,
F6) using sodium alginate and Calcium chloride as
a polymer. These Microspheres were prepared as
described above same as alginate-ethyl cellulose
Microspheres, with a slight modification. In this
pectin was mixed along with weighed quantity
(200mg) saxagliptin and dispersed in 50ml sodium
alginate solution.
Evaluation parameters of microspheres:
Measurement of Micromeritic Properties of
Microspheres:
Granulometric Study
The particle size has very significant effect on the
release profile of Microspheres. Granulometric
study was conducted to determine the particle size
distribution pattern. For this study sieve analysis
was carried out on mechanical sieve shaker, using
different meshes (#12, #16, #22, #30) of American
Society of Testing Materials (ASTM). The size
distribution of Microspheres is reported in table
no.3.
Flow Property
The flow properties were investigated by
measuring the angle of repose of drug-loaded
Microspheres using fixed-base cone method to
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Sodium alginate(w/v)
CaCl2 (w/v)
1%
3%
1.5%
5%
2%
7%
0.5%
5%
0.75%
5%
1.0%
5%
assess the flowability.
The fixed-base cone method, a funnel was secured
with its tip at a 1cm height (H) above the graph
paper that was placed on a flat horizontal surface.
Microspheres were carefully poured through the
funnel until the apex of the conical pile just
touched the tip of the funnel. Measure the height
of he pile (h) and the radius of the base (r) with
ruler. The angle of repose was determined by
using the equation, and reported in table no.4.
tan = H/R
or
= tan-1 H/R
= angle of repose,
R = radius of the base of pile
H = height of pile.
Bulk and tapped density
The bulk and tapped densities were measured
in a 10ml graduated measuring cylinder to
measure packability of the Microspheres. The
sample contained in the measuring cylinder was
tapped mechanically by means of constant
velocity rotating cam with change in its initial bulk
density to a final tapped density when it has
attained its most stable form. Each experiment was
carried out in triplicate. The bulk and tapped
density can be determined and reported in table
no.4.
Particle size analysis
Particle size analysis of drug-loaded Microspheres
was performed by optical microscopy (Olympus
Model Szx-12). A small amount of microspheres
was suspended in purified water (10ml). Mount the
sample on a clean glass slide and placed it on
mechanical stage of the microscope. The eye
piece of microscope fitted with a micrometer by
which the size of the beads could be determined.
The process was repeated for each batch of
prepared Microspheres and mean particle size can
be reported in table no.4.
Where
Surface study
The surface morphological details of the
Microspheres were determined by using a scanning
electron microscope (SEM) model JSM, 35CF
JEOL, Japan.The samples were dried thoroughly
in vacuum desicator before mounting on brass
specimen studies. The samples were mounted
on a specimen studies using double sided
adhesive tape, and gold-palladium alloy of 120
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IAJPS 2016, 3 (6), 627-636
Naresh N S and Pratyusha A
Kness was coated on the sample using spatter
coating unit (Model E5100 Polar on, UK) in an
argon ambient of 8-10 pascal with plasma
voltage about 2Kv and discharge current about
20mA. The sputtering was done for nearly
3minutes to obtain uniform coating on the samples
to enable good quality SEM images. The SEM
operated at low accelerating voltage of about
15Kv with load current of about 80mA The
condenser lens position was maintained bet ween
4.4 5.1. The objective lens aperture has a
diameter of 240 microns and the working
distance WD = 39mm.
Loose-Surface Crystal Study
In this study accurately weighed 25mg of
Microspheres (#16) was suspended in the
phosphate buffer pH 6.8 and was shaken
vigorously for 5min. The drug leached out from
the surface of the micro pellets was analyzed
at 243nm wavelength spectrophotometrically.
Swelling Properties
The swelling properties of prepared Microspheres
were determined in acidic buffer pH 1.2. Thirty
dried beads were placed in a beaker to which
200ml of buffer solution and then stirred with a
magnetic stirrer at a speed 50 rpm. After 1hr
interval, the equilibrium swollen beads were
observed and measured under optical microscope.
The magnitude of swelling was presented by the
ratio of the mean diameter of swollen beads to the
mean diameter of the dried beads before the test
swown in table 6.
Drug Entrapment Efficiency (DEE)
Drug entrapment efficiency of Microspheres was
performed by accurately weighed 50mg of
Microspheres were
suspended
100ml
of
phosphate buffer pH 6.80.1. The resulting
solution was kept for 24 hours. Next day it was
stirred for 15 min and subjected for filtration. After
suitable dilution, saxagliptin content in the filtrate
was analyzed spectrophotometrically at 210nm
using
Shimadzu
1201
UV-visible
spectrophotometer. The obtained absorbance was
plotted on the standard curve to get the exact
concentration of the entrapped drug. Calculating
this concentration with dilution factor we get the
percentage of actual drug encapsulated in
Microspheres.
The drug entrapment efficiency was
determined using following relationship:%DEE =
Actual Drug Content
x 100
Theoretical Drug Content
The results of DEE (Drug Entrapment Efficiency)
are reported in table no.5.
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In-vitro Dissolution Studies:
The physicochemical property of most drugs that
has greatest influence on their absorption
characteristics from the GIT is dissolution rate.
The drug is expected to release from the solid
dosage forms (granules, tablets, capsules etc) and
immediately go into molecular solution. This
process is called as dissolution.
Drug Release Studies
The method is specified in USP for drug release
study was followed:
Apparatus:- USP II dissolution rate test
apparatus employing the round bottom dissolution
vessel and rotating paddle assembly.
Acid Stage:- 900ml of simulated gastric fluid TS
(acid buffer pH 1.20.05 without enzymes.
Buffer stage:- 900ml of pH 6.8 (duodenal fluid)
and simulated intestinal fluid TS (phosphate
buffer pH 7.40.05 without enzymes.
Procedure:- Microspheres equivalent to 100mg of
Saxagliptin and were evaluated for in-vitro
dissolution studies. The study was carried out in
a USP II rotating paddle apparatus. Dissolution
fluid
consists
of 900ml
of
simulated
gastrointestinal fluids of increasing pH namely
pH 1.2 (-2 hr), pH 6.8 (1hr) and pH 7.4 (up to 10
hrs) maintained temperature at 370C0.50C and
the basket was rotated at a constant speed of
50rpm.
Aliquots of samples were withdrawn after
predetermined periods of time and the same
volume of fresh medium was added immediately to
the test medium. The withdrawal samples were
filtered through a 0.45m membrane filter. The
drug content was determined in the filtrate after
appropriate dilution and analyzed at 210 nm
spectrophotometrically using Shimadzu 1201 UVvisible
spectrophotometer.
Corresponding
concentrations in the samples were calculated from
standard plot and calculate cumulative percentage
of drug release from each formulation.
Kinetic study:
The data obtained from the in-vitro dissolution
studies subjected for kinetic treatment to obtain the
order of release and best fit model for the
formulations by using PCP-Disso-V2 software.
RESULTS AND DISCUSSION:
In the present work Saxagliptin microspheres were
prepared by ionotropic gelation technique using
sodium alginate and also with three different
coating polymers. Total nine batches of
microspheres (F1-F6) were prepared and
investigated the physico-chemical properties like
granulometric study, flow properties, particle size,
drug-entrapment efficiency, swelling properties,
scanning electron microscopy, loose-surface
crystal study and in-vitro drug release behaviors.
Preformulation studies:
Calibration development for Saxagliptin adopting
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IAJPS 2016, 3 (6), 627-636
Naresh N S and Pratyusha A
spectro photometric technology. The max of
Saxagliptin at 210nm were identified using UVVisible spectrophotometry. A standard curve from
the stock solution was obtained in the range of
2-12 g/ml concentrations using p H 1.2 (acid
buffer), pH 6.8 (phosphate buffer) by measuring
absorbance at 210 nm.
The absorbance values are given in table 2 and the
max, standard plots of Saxagliptin are shown in
figures 1,2 and 3.
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The IR spectra of drug-sodium alginate did not
show much change. The possibility of interaction
was ruled out as there was no major shift in
absorption bands of the drug and physical mixtures
shows that there is no appearance or disappearance
of peaks. It is, therefore, expected the drug and
polymer are compatible and free from chemical
interactions.
Table 2: standard calibration curve for Saxagliptin
S.No.
1
2
3
4
5
6
Concentration (g/ml)
2
4
6
8
10
12
Absorbance at 210 nm
0.026
0.032
0.048
0.062
0.075
0.090
0.098
0.119
0.122
0.148
0.144
0.178
Fig 1: Spectrum of Saxagliptin 210nm
0.2
Absorbanc
e
0.15
PH 1.2
0.1
0.05
Linear (PH
1.2)
0
0
10
15
Concentratio g/ml)
.
Fig 2: standard calibration curve of Saxagliptin
at pH 1.2
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standard calibration curve of
Saxagliptin
y = 0.0149x
0.2
R = 0.9999
Absorbance
Standard Calibration curve of
Saxagliptin
y = 0.0122x
R = 0.9995
0.15
PH 6.8
0.1
Linear (PH
6.8)
0.05
0
0
10
15
Concentration(g/ml)
.
Fig 3: standard calibration curve of Saxagliptin
at pH 6.8
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IAJPS 2016, 3 (6), 627-636
Naresh N S and Pratyusha A
Granulometric Study
In the granulometric study, the size distribution o f
the micro sp her es in d if f er ent sieves were
o b served table no.3, and found that 42.46% to
79.50% of microspheres were retained in #20
sieve, which proves the uniformity
size
of
microspheres. On other hand with increase in the
Flow Property
The flow properties of the prepared formulations
were determined by measuring the angle of
repose, using fixed-base cone method. All the
formulations showed an acceptable range of
angle of repose. The determined range of the
formulations as reported in table no.4.
Particle Size
Particle size of drug-loaded microspheres was
measured by optical microscopy. The size of the
spheres was obtained in the range 1 to1000 m.
The mean diameter of the particles was found to
decrease by increasing in the concentration of
calcium chloride solution and also increasing in the
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concentration of coating polymers in the
formulated microspheres of batch F1, F2,
F3(Sodium alginate) F4, F5, F6 (Pectin), F7, F8,
F9 (Sodium CMC) and observed that the
distribution of the particle size slightly shifts to the
lower pore size due to increase in the physical
behaviors of the microspheres.
concentration of sodium alginate by increase in the
diameter of the particles. The mean diameter of the
microspheres is reported in table no4.
Scanning Electron Microscopy:
The physical parameters like shape and particle
size were analyzed by scanning electron
microscopes62, which was presented for
determining the surface and size. The SEMs of the
formulation showed that the spheres are having the
size-range within the standard limits.
From the photo micrographic observation it can
be stated that bridging and dense nature of the
formulation batches F3 were significantly prolong
the drug release compared with other formulation
batches.
Fig 4: SEM analysis for Saxagliptin + sodium alginate
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Naresh N S and Pratyusha A
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Fig 5: FTIR Spectra of Saxagliptin
Fig 6: FTIR Spectra of Saxagliptin + sodium alginate
Drug entrapment efficiency:
The drug entrapment efficiency of all the batches
are shown in table 5. The batches F1, F2 and F3
shows the drug entrapment efficiency values of
70.4%,77.2% and 85.3% respectively. Drug
entrapment efficiency of microspheres increase
with increasing in the percentage of sodium
alginate as well as by concentration of coating
polymers like ethyl cellulose and pectin. The
observations are still further depicts the drug
entrapment efficiency of batch F4 and F5,F6
were 89.9% and 90.7% respectively. These may
be due to drug adhering property of the polymers
and also reduced the loss of drug in the curing
medium and formation of dense matrix structure
shows increase in the drug entrapment efficiency
of the Microspheres. The amount of calcium
chloride has probably no significant effect on the
drug entrapment efficiency.
Table 3: percentage of weight remained on various sieves
Batch
no.
F1
F2
F3
F4
F5
F6
#12 (1.68mm)
1190-1680m
8.40
5.15
4.78
5.97
8.67
5.86
#16 (1.19mm)
840-1190m
7.50
22.83
27.13
34.35
38.92
49.96
#20 (0.84mm)
590-840m
79.50
68.40
63.62
57.82
51.40
42.46
#30 (0.59mm)
297-590m
4.60
3.62
4.47
1.86
1.01
1.72
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Table 4: Micromeritic properties of drug loaded microspheres
Angle of Repose ()
Batch
no.
F1
F2
F3
F4
F5
F6
32.25
30.15
28.20'
26.20'
25.30'
25.40'
Bulk Density
(g/ml)
0.485
0.695
0.785
0.735
0.764
0.725
Tapped Density
(g/ml)
0.693
0.755
0.862
0.806
0.810
0.835
Mean diameter
(m)
822.15
794.25
778.50
860.15
890.55
970.60
Table 5: Drug entrapment efficiency of microspheres
S. No.
Theoretical Drug Content
(%)
82.38
80.26
8.53
74.77
72.86
80.17
F1
F2
F3
F4
F5
F6
ActualDrug Content (%)
58
62
67
68
69
72
Drug Entrapment efficiency
(%)
70.405
77.248
85.317
90.945
94.702
89.921
Table 6: swelling properties of drug loaded microspheres in different time periods at pH 1.2
Mean diameters of microspheres (m)
Formulation
Code
F1
F2
F3
F4
F5
F6
0 hr
522.15
494.25
478.50
560.15
590.55
670.60
Swelling Properties:
The Swelling-dissolution-erosion process is
highly complex. In systems based on sodium
alginate cross-linked with calcium chloride, the
osmotic pressure gradient that exists between the
alginate gel and the environment comprises an
important factor in the swelling process. Under
acidic conditions swelling of calcium alginate
spheres scarcely occurs.
The observations of swelling properties of the
microspheres in pH 1.2 were reported in table
6.The swelling behavior of the prepared
Microspheres was studied in pH 1.2 up to 2 hrs.
Increasing concentration of calcium chloride in the
counter ion solution produces spears with higher
levels of Ca2+ ions will reduces the swelling of the
spears,
consequently
increasing
the
concentration
cross-linking
polymers
also
decreasing of the swelling properties of the
spears in acidic medium. Due to increased
dissolution behavior of the Microspheres in the
pH 6 . 8 the swelling behavior study was not
disintegration
and
dissolution
of
1 hr
2 hr
638.60
606.15
587.50
684.05
605.65
696.40
662.30
623.40
603.20
610.40
631.30
729.10
carried out in those phosphate buffers.
In-vitro Dissolution Studies:
The dissolution studies were conducted by using
three different dissolution mediums simultaneously
in pH 1.2 for 2 hrs, then the spears shifted at pH
6.8 determined studied up to 09 hrs. The results of
the in-vitro dissolution studies of formulations
F1 to F6 as shown in table 7 . The plots of
cumulative percentage drug release V/s time as
shown in figure 7.
The in-vitro release data shows the % cumulative
drug release at 14 hours for batch F3 in range
95.54 w/w. Whereas % cumulative drug release at
batch F4 ,F5and F6 were 85 to92% w/w. The
formulated Microspheres showed increase in drug
at pH 1.2 and trend is continued in pH 6.8 because
due to cross-linking takes place only between
carboxylate residue of GG-blocks and Ca2+ ions
forms a tight-gel network structure. The toughness
of the network structure and subsequent
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Naresh N S and Pratyusha A
alginate
particles
taking
place
through
ionexchange
between
the
bound Ca+2 ions and Na+ ions present in
some extent. Thus the release of Saxagliptin from
the microspheres appears to be significantly with
increase in initial alginate concentration but not
with calcium ions.
The kinetic data of in-vitro release proves that the
aim of the research to formulate sustained release
drug formulations for Saxagliptin using sodium
alginate and different coating polymers.
The estimated physicochemical and in-vitro release
data proves that the formulated Saxagliptin
Microspheres having the characteristics that
required for the formulation of sustained release
dosage forms.
However, it can be proved the release drug may be
retarded and produce proper sustained effect in the
formulation F3 was showing better sustained
release pattern when compared to the other
batches.
Further, all the formulations were subjected for
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dissolution medium leading to extended release to
mathematical treatment to check whether the
release is following first-order or zero-order
kinetics.
The drug diffusion coefficient and correlation
coefficient
were assessed using
various
mathematical models using PCP Dissco-V2
software and reported in table 8.
The values of coefficient of correlation (r) were
calculated and was found to be more linear for
zero order release as compared to first-order. It
was concluded that release of drug from
formulation batches F1 to F6 followed Zero order
kinetics.
The kinetic data was best fitted to KorsmeyerPeppas model. The values of diffusion coefficient
(n) for formulation F3 shows to be 0.8674,
diffusion
following
non-Fickian
transport
mechanism.
Table 7: In-vitro release kinetic data of drug loaded microspheres containing sodium alginate
F1
F2
F3
F4
F5
F6
0
2
0
14.850.45
0
19.821.33
0
18.14 1.76
0
13.23 1.43
0
12.281.32
0
12.21 1.44
26.710.99
32.141.65
29.25 1.78
25.23 1.66
22.120.87
23.181.44
38.821.23
46.521.83
42.451.61
36.48 1.99
36.54 0.78
34.630.89
52.141.12
59.611.61
58.621.43
51.711.39
49.821.27
45.441.23
10
65.611.18
72.231.77
69.231.5
66.851.44
60.140.37
57.230.99
12
78.231.87
85.451.22
81.451.72
79.331.37
74.830.83
72.451.19
14
88.231.45
91.331.83
95.541.85
92.411.29
89.801.41
85.221.17
Cumulative % Drug Release
Time in
Hours
120
100
F1
80
F2
60
F3
40
F4
20
F5
F6
0
10
12
14
Time in Hours
Fig 7: In vitro Cumulative percentage Drug Release of Formulations F1, F2, F3, F4 F5 & F6
www.iajps.com
Page 634
IAJPS 2016, 3 (6), 627-636
Naresh N S and Pratyusha A
ISSN 2349-7750
Table 8: Model fitting data of the release profile for saxaglptin using five different models (r-values)
Mathematical Models (Kinetics)
Formulation
Code
Zero Order
First
Order
Higuchi
Matrix
Krosmeyer
Peppas
Hexan
crowell
F3
0.953
0.879
0.960
0.613
0.932
CONCLUSION:
Sustained release formulation of Saxagliptin was
successfully prepared using sodium alginate by
Ionotropic Gelation Technique. The in vitro
dissolution data showed sustained release of the
formulation up to 10 hours. The microspheres were
prepared without the use of organic solvents.
Microspheres of Saxagliptin decrease the incidence
of side effects and also improve patient compliance
by reducing the number of dosings and by reducing
the fluctuations of drug in the blood.
In the present study six formulations were
formulated by using sodium alginate as drug release
modifiers in various proportions, and evaluate
their physicochemical properties and in-vitro drug
release potential. Results of preformulation study,
granulometric study, bulk and tapped density, mean
particle size, angle of repose, drug- entrapment
efficiency, in-vitro dissolution study, In-vitro
release study of formulations F1, F2, F4, F5 and
F6 showed a release slowly to some extent with
increased percentage of sodium alginate.
The Microspheres were further subjected to surface
and particle size determination by scanning electron
microscopy wherein formulations F3 containing
sodium alginate as polymers showed bridging which
indicated for dense nature, low porosity of the
coating materials and larger particle size.
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