98

Research Article
International Journal of
Pharmacy and Industrial
Available Online at: www.ijpir.com
Research

Print 2231 – 3648

ISSN
Online 2231 – 3656

Formulation and evaluation of colon ivermectin immediate release tablets

by using natural polymers
B. Shirisha*1, M. Ajitha 2
1
CMR College of Pharmacy, Kandlakoya (V), Medchal, Hyderabad
2
Jawaharlal Nehru Technological University, IST, CPS, Hyderabad.

ABSTRACT
In the present study it has been aimed at developing pH sensitive tablets of Ivermectin for local action in
proximal colon, with a view of minimizing the drug release in the physiological environment of stomach and
small intestine and to ensure maximum drug release in the physiological environment of proximal colon with an
improved patient compliance, least side effects, better drug therapy and all aspects of an ideal drug delivery
system. In present work attempt was made to formulate and evaluate colon tablets of ivermectin. Attempts were
made to achieve immediate drug release from the dosage form. Twenty seven formulations (F1-F27) were
prepared by direct compression method using 3 3 Response surface method where 3 3 indicates 3 variables and 3
levels of natural superdisintegrants like Gellan Gum, Locust bean Gum and Fenugreek seed Gum (low, middle
and high concentrations) by using Design of experiment software. In the Preformulation properties was carried
out and the values obtained were within the range. And FTIR studies results revealed that there was no
incompatibility between drug and excipients. Thus, colon Tablets were formulated by varying proportions of
natural superdisintegrants by direct compression method and all formulations were coated by Eudragit RS 100
coating solution which is a pH sensitive polymer to prevent drug release in stomach and intestine. Entire drug
will release in proximal part of colon.

Keywords: Ivermectin, Superdisintegrants, Gellan Gum, Locust bean Gum and Fenugreek seed Gum

INTRODUCTION of administration [1, 2] . During the last decade

there has been interest in developing site-specific
The oral route of drug administration is the
formulations for targeting drug to the colon.
most convenient and important method of
Colonic drug delivery has gained increased
administering drugs for systemic effect. Nearly
importance not just for the delivery of the drugs for
50% of the drug delivery systems available in the
the treatment of local diseases associated with the
market are oral D.D.S. and these systems have
colon like Crohn’s disease, ulcerative colitis,
more advantages due to patient acceptance and ease
irritable bowel syndrome and constipation but also
________________________________

Author for Correspondence:

B. Shirisha
CMR College of Pharmacy,
Kandlakoya (V), Medchal, Hyderabad
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for the systemic delivery of proteins, therapeutic Standard solution

peptides, antiasthmatic drugs, antihypertensive
100 mg of Ivermectin was dissolved in solvents
drugs and antidiabetic agents [3, 4] . There are
like 0.1N HCl, Phosphate buffer pH 6.8 and
various methods or techniques through which colon
Phosphate buffer pH 7.4 in100mL volumetric
drug targeting can be achieved, for example,
flasks separately and the solution was made up to
formation of prodrug, coating with pH-sensitive
volume with rest solvent.
polymers, coating with biodegradable polymers,
designing formulations using polysaccharides, Preparation of colon tablets of Ivermectin
timed released systems, pressure controlled drug Twenty seven formulations (F1-F27) were
delivery systems, osmotic pressure controlled prepared by direct compression method using 3 3
systems [5, 6] . Coating of the drugs with pH Response surface method (3 variables and 3 levels
sensitive polymers provides simple approach for of polymers) by using Design of experiment
colon specific drug delivery. software with natural superdisintegrants like Gellan
In the present study it has been aimed at Gum, Locust bean Gum and Fenugreek seed Gum.
developing pH sensitive tablets of Ivermectin for All the formulations were varied in concentration
local action in proximal colon, with a view of of natural superdisintegrants, magnesium stearate
minimizing the drug release in the physiological constituted in all the formulations. All the
environment of stomach and small intestine and to ingredients were passed through sieve no 85# and
ensure maximum drug release in the physiological were mixed uniformly. Direct compression was
environment of proximal colon with an improved carried out with sufficient quantity of binder (PVP
patient compliance, least side effects, better drug K 30). Tablets were compressed with 6 mm flat
therapy and all aspects of an ideal drug delivery punch (Cadmach, Ahmedabad, India) [10].
system.
pH sensitive coating of prepared compression
tablets
MATERIALS AND METHODS
Compression tablets of ivermectin were further
Estimation of Ivermectin [7, 8, 9] coated with pH sensitive coating polymers by dip
The following methods are available for the coating method. Required quantity of Eudragit RS
estimation of Ivermectin. 100 was dissolved in acetone using a magnetic
stirrer. After complete solubilisation of polymer,
Spectrophotometric method castor oil (10% w/w of dry polymer) was added as
The predetermined maxima wavelength i.e., 254 plasticizer. Talc (0.1% w/v) was added as
nm in 0.1N HCl, Phosphate buffer pH 6.8 and antiadherant and the solution was stirred for 15
Phosphate buffer pH 7.4 was adopted in the min. Pre-weighted compression tablets were dipped
assessment of Ivermectin in dissolution and assay for 3-5 times into the solution until 10% weight
techniques. gain [11].

Table 1: Formulation trials of colon tablets of Ivermectin

F.NO Ivermectin Gellan Locust Fenugreek PVP Mannitol Mg Talc TOTAL
Gum bean seed gum K- Stearate
gum 30
F1 9 10 8 6 4 59 2 2 100
F2 9 12 8 6 4 57 2 2 100
F3 9 14 8 6 4 55 2 2 100
F4 9 10 10 6 4 57 2 2 100
F5 9 12 10 6 4 55 2 2 100
F6 9 14 10 6 4 53 2 2 100
F7 9 10 12 6 4 55 2 2 100
F8 9 12 12 6 4 53 2 2 100

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F9 9 14 12 6 4 51 2 2 100
F10 9 10 8 8 4 57 2 2 100
F11 9 12 8 8 4 55 2 2 100
F12 9 14 8 8 4 53 2 2 100
F13 9 10 10 8 4 53 2 2 100
F14 9 12 10 8 4 53 2 2 100
F15 9 14 10 8 4 51 2 2 100
F16 9 10 12 8 4 53 2 2 100
F17 9 12 12 8 4 51 2 2 100
F18 9 14 12 8 4 51 2 2 100
F19 9 10 8 10 4 55 2 2 100
F20 9 12 8 10 4 53 2 2 100
F21 9 14 8 10 4 51 2 2 100
F22 9 10 10 10 4 53 2 2 100
F23 9 12 10 10 4 51 2 2 100
F24 9 14 10 10 4 49 2 2 100
F25 9 10 12 10 4 51 2 2 100
F26 9 12 12 10 4 49 2 2 100
F27 9 14 12 10 4 47 2 2 100

Table 2: Composition of coating solution

S. No Composition Quantity
1 Eudragit RS 100 10% w/v
2 Acetone 95 ml
3 Water 5 ml
4 Castor oil 0.1% w/v
5 Talc 0.1% w/v
Total weight gain + 10% w/v

EVALUATION TESTS remain below the surface of the liquid on their

upward movement and descend not closer than
Pre compression evaluation tests [12, 13, 14]
2.5cm from the bottom of the beaker.
Angle of repose, bulk density, tapped density,
compressibility index (carr’s index), hausner’s ratio In Vitro Drug Dissolution Study
were performed The dissolution of prepared colon tablet
formulations was carried out by obeying below
POST COMPRESSION EVALUATION
conditions; Dissolution Apparatus USP Dissolution
TESTS
Apparatus Type II (Paddle), Dissolution Medium
Weight variations, Thicknesses, Hardness, 0.1N HCL pH 1.2Phosphate buffer pH 6.8
Friability, and Content Uniformity were performed Phosphate buffer (pH 7.4), Dissolution Medium
Volume was 900ml, Temperature was 37±0.2°C,
In-vitro disintegration time
Estimation was 254 in UV Spectrophotometer,
The USP device to rest disintegration was six Time Intervals (Hours) 12,3,4,5,6 & 7
glass tubes that are “3 long, open at the top, and
held against 10” screen at the bottom end of the Kinetic Model Fitting [15, 16, 17]
basket rack assembly. One tablet is placed in each There are several linear and non-linear kinetic
tube and the basket rack is poisoned in 1 liter models to describe release mechanisms and to
beaker of buffer at 37± 2 0C, such that the tablets

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compare test and Reference dissolution profiles are of the drug (Ivermectin) in presence of other
as follows: excipients before formulation were determined by
 Zero order kinetics various techniques like Infrared Spectroscopy (IR)
 First order kinetics with which future complications can be
 Higuchi investigated and predicted. [18]
 Korsmeyer-Peppas model Compatibility check by FTIR Studies
Drug-excipient compatibility studies FTIR spectra of Pure Drug sample and its
While development of new drug delivery physical mixture along with formulation additives
systems the drug will be influenced a lot by of colon tablets and Optimized formulation were
excipients and solvents used and may lead to testaments with FTIR instrument.
degradation of drug so, the stability and purity

Table 3: Kinetic Model Fitting

Release exponent (n) Drug transport mechanism Rate as a function of time
0.5 Fickian diffusion t-0.5
0.5<n<1.0 Anomalous transport tn-1
1.0 Case-II transport Zero-order release
Higher than 1.0 Super Case-II transport tn-1

This type of analysis of release behavior is immutability studies in accordance with guidelines
valuable is to the formulator for comparative of ICH stability protocol. The test specifications
purposes. The Release exponent can be obtained include Temperature of 40 0C ± 2 0C and relative
from the slope and the Constant (K k) obtained from humidity of 75±5% RH for a time period of 6
the intercept of the graphical relation between months in Humidity chamber (REMI, Mumbai).
logarithmic versions of left side of the equation The specifications to be evaluated in stability study
versus log t. period include Content Uniformity, Hardness and
in vitro drug release [19]
Stability studies
Among all tablets compressed of distinct
batches, mucoadhesive tablets were subjected to

RESULTS AND DISCUSSION

Figure 1: Standard calibration graph of Ivermectin at pH 7.4

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FTIR Spectrum of pure ivermectin

Figure 2: FTIR Spectrum of pure ivermectin

Table 4: FTIR interpretation of ivermectin

Functional groups Reference peak (cm-1) Observed peak(cm-1)
Cyclic amines 3200-3500 3250
C-H stretching 3000-2840 2950
O-H bending 1470-1395 1459.20
C-Cl 1000-925 990.91

FTIR Spectrum Ivermectin optimized formulation

Figure 3: FTIR Spectrum Ivermectin optimized formulation

Table5: FTIR interpretation of ivermectin optimized formulation

Functional groups Reference peak (cm-1) Observed peak(cm-1)
Cyclic amines 3200-3500 3281.89

C-H stretching 3000-2840 2949.44

O-H bending 1470-1395 1462.08

C-Cl 1000-925 959.28

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Physical parameters of prepared powder blends of colon DDS

Table 6: Physical properties of prepared powder blends of colon tablet
Formulation Bulk density Tapped density Angle of repose () Carr’s index Hausner ratio
code (g/cc) (g/cc) (%)
F1 0.54±0.19 0.52±0.15 24.34±0.44 09.23±1.12 1.13±0.24
F2 0.57±0.16 0.58±0.17 22.67±0.31 08.23±1.42 1.11±0.10
F3 0.57±0.17 0.64±0.21 26.54±0.41 10.12±0.8 1.13±0.20
F4 0.59±0.25 0.68±0.25 25.89±0.55 11.34±0.6 1.14±0.24
F5 0.57±0.18 0.59±0.18 22.56±0.0.57 12.23±0.12 1.11±0.32
F6 0.58±0.20 0.66±0.20 25.30±0.30 11.23±0.25 1.12±0.30
F7 0.51±0.14 0.64±0.16 22.56±0.57 10.34±0.31 1.14±0.20
F8 0.54±0.16 0.68±0.17 23.67±0.60 09.11±0.24 1.12±0.25
F9 0.65±0.18 0.61±0.19 25.56±0.44 09.45±1.15 1.13±0.70
F10 0.66±0.25 0.67±0.18 21.66±0.31 13.45±1.3 1.15±0.20
F11 0.51±0.17 0.68±0.16 22.34±0.37 14.23±1.5 1.13±0.16
F12 0.55±0.16 0.64±0.20 25.99±0.70 11.34±1.25 1.12±0.12
F13 0.56±0.19 0.66±0.18 23.14±0.50 09.67±1.55 1.09±0.14
F14 0.52±0.13 0.66±0.17 22.09±0.57 10.23±1.55 1.14±0.15
F15 0.51±0.18 0.63±0.16 24.78±0.77 10.45±1.5 1.15±0.15
F16 0.52±0.13 0.61±0.15 23.45±0.80 09.681.3 1.18±0.18
F17 0.58±0.13 0.68±0.19 21.09±0.86 09.47±1.09 1.12±0.15
F18 0.56±0.16 0.67±0.20 23.05±0.75 14.99±1.20 1.14±0.15
F19 0.54±0.18 0.61±0.16 26.06±0.67 12.45±1.45 1.13±0.15
F20 0.58±0.17 0.64±0.17 23.78±0.57 13.12±1.45 1.15±0.17
F21 0.59±0.13 0.63±0.18 25.34±0.70 11.09±1.07 1.16±0.20
F22 0.58±0.15 0.67±0.12 25.12±0.35 14.34±1.06 1.17±0.30
F23 0.55±0.14 0.64±0.21 26.45±0.37 10.67±1.25 1.14±0.35
F24 0.54±0.16 0.64±0.12 25.56±0.31 09.68±1.35 1.14±0.15
F25 0.52±0.19 0.68±0.14 23.67±0.44 13.24±0.24 1.11±0.16
F26 0.51±0.19 0.65±0.16 24.12±0.16 09.39±0.25 1.17±0.18
F27 0.54±0.20 0.64±0.13 22.56±0.43 12.05±0.31 1.18±0.15
Above parameters are communicated as Average ± Standard Deviation; (n=3)

The results of bulk densities formulations The Hausner’s ratio values in the range of 1.11
bearing F1 to F27 reported being in the range of to 1.18 %. These findings indicated that the all the
0.51g/cc to 0.66g/cc. The findings of tapped batches of formulations exhibited good flow
density formulations F1 to F27 reported being in properties.
the range of 0.52g/cc³ to 0.68g/cc³. The angle of
Physico-chemical properties of ivermectin
repose of all the formulations was found
colon tablets
satisfactory results. The formulation F17 was found
to be 21.09 having good flow property. The prepared tablets were evaluated for
The compressibility index values were found to different physicochemical properties and the results
be in the range of 8 to 15 %. These findings are found to be within the pharmacopoeial limits,
indicated that the all the batches of formulations which depicted in Table 7
exhibited good flow properties.

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Table 7: Physico-chemical parameters of ivermectin colon core tablets

F.No *Weight #Thickness #Hardness #Friability #Content Disintegration
variation (mm) (Kg/Cm2) (%) uniformity tests
(mg) (%) (Secs)
F1 100.12±0.20 3.1±104 4.1±0.13 0.51±0.08 97.23±1.23 58±0.27
F2 99.23±0.24 3.01.16 4.0±0.33 0.54±0.09 98.04±1.03 77±0.53
F3 98.08±0.15 3.1±1.05 4.3±0.13 0.63±0.07 96.56±0.94 76±0.51
F4 101.09±0.70 3.2±1.09 4.2±0.10 0.56±0.05 98.11±0.63 66±0.93
F5 101.89±0.50 3.1±1.37 4.1±0.10 0.61±0.07 95.23±0.81 55±0.43
F6 100.34±0.20 3.2±1.11 4.2±0.10 0.67±0.09 96.45±0.32 70±1.04
F7 100.23±0.60 3.0±1.61 4.0±0.15 0.54±0.02 95.11±1.17 68±0.64
F8 99.12±0.50 3.2±0.3 4.2±0.15 0.67±0.02 98.23±0.45 50±0.60
F9 100.23±0.48 3.2±0.45 4.2±0.19 0.56±0.02 97.13±1.17 59±0.64
F10 100.24±0.20 3.1±0.25 4.1±0.21 0.77±0.07 96.23±0.49 75±0.65
F11 101.45±0.97 3.1±0.70 4.4±0.10 0.76±0.05 98.97±0.95 44±0.75
F12 02.03±0.54 3.4±0.25 4.6±0.15 0.73±0.08 98.45±0.35 56±0.51

F13 101.04±0.30 3.5±0.60 4.8±0.18 0.52±0.09 99.85±0.24 58±0.78

F14 98.23±0.35 3.1±0.56 4.2±0.10 0.72±0.02 99.18±0.13 81±0.83
F15 99.34±0.25 3.5±0.70 .6±0.08 0.71±0.20 99.25±1.21 89±0.63
F16 101.12±0.55 3.1±0.40 4.2±0.21 0.78±0.9 97.45±1.30 86±0.43
F17 100.23±0.50 3.5±0.17 4.7±0.04 0.79±0.04 99.94±1.31 37±0.97
F18 101.67±0.30 3.5±0.40 4.6±0.14 0.82±0.03 98.56±1.36 44±0.87
F19 99.13±0.45 3.0±0.17 4.0±0.12 0.84±0.01 97.29±1.31 49±1.13
F20 99.45±0.55 3.3±0.96 4.5±0.10 0.63±0.03 97.18±1.36 58±1.23
F21 98.12±0.70 3.2±0.50 4.3±0.12 0.66±0.03 96.27±1.30 50±1.27
F22 101.45±0.80 3.0±0.63 4.0±0.10 0.72±0.015 99.34±1.16 41±0.83
F23 100.23±0.55 3.3±0.78 4.8±0.17 0.76±0.04 99.14±1.46 66±1.21
F24 100.12±0.60 3.4±0.86 4.7±0.14 0.73±0.06 99.16±0.56 51±0.93
F25 99.14±0.75 3.1±0.57 4.6±0.15 0.67±0.07 98.23±0.84 63±0.92
F26 100.18±0.15 3.3±0.63 4.7±0.18 0.72±0.03 98.34±1.16 55±0.18
F27 100.23±0.75 3.6±0.98 4.9±0.05 0.89±0.04 98.10±1.11 63±1.25
*Values are expressed in mean± SD :( n=20)
#Values are expressed in mean± SD :( n=3)

The Weight variation of all formulations within The friability of all prepared formulation is
the limit because weight variation deviation is ± 5 between 0.53-0.89.the friability properties limits
for tablet and weight above 100 mg. The measured are in between 0-1%. The drug content of all
hardness of the tablets of each batch of all formulation is in between 95.00-99.94%, drug
formulations i.e. F1 to F27 was ranged between 4.0 content depends on the angle of repose since the
to 5.0 Kg/cm2 and the results are shown in Table…. angle of repose indicates uniform flow nature of
The thickness of the tablets was found to be almost powder blend which makes the drug to evenly
uniform in all formulations F1 to F27. The distribute in all the formulation and to maintain
thickness of all the formulations between the content uniformity in all batches.
ranges 3.0-3.6 mm.

Table 8: Physico-chemical parameters of ivermectin colon coated tablets

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*Weight variation F.No #Thickness #Hardness #Friability

(mg) (mm) (Kg/Cm2) (%)
F1 110.12±0.20 3.6±104 4.7±0.13 0.41±0.08
F2 109.23±0.24 3.9.16 4.6±0.33 0.44±0.09
F3 109.08±0.15 3.7±1.05 4.9±0.13 0.53±0.07
F4 111.09±0.70 3.9±1.09 4.5±0.10 0.36±0.05
F5 111.89±0.50 3.6±1.37 4.9±0.10 0.51±0.07
F6 110.34±0.20 3.8±1.11 4.7±0.10 0.47±0.09
F7 110.23±0.60 3.9±1.61 4.8±0.15 0.44±0.02
F8 109.12±0.50 3.7±0.3 4.7±0.15 0.57±0.02
F9 110.23±0.48 3.8±0.45 4.6±0.19 0.46±0.02
F10 110.24±0.20 3.6±0.25 4.5±0.21 0.57±0.07
F11 111.45±0.97 3.7±0.70 4.8±0.10 0.56±0.05
F12 112.03±0.54 3.9±0.25 4.9±0.15 0.53±0.08
F13 111.04±0.30 3.8±0.60 5.2±0.18 0.52±0.09
F14 108.23±0.35 3.7±0.56 4.9±0.10 0.42±0.02
F15 109.34±0.25 3.9±0.70 4.9±0.08 0.5 1±0.20
F16 111.12±0.55 3.8±0.40 4.8±0.21 0.58±0.9
F17 110.23±0.50 3.8±0.17 5.5±0.04 0.49±0.04
F18 111.67±0.30 3.8±0.40 4.8±0.14 0.52±0.03
F19 109.13±0.45 3.7±0.17 4.5±0.12 0.54±0.01
F20 109.45±0.55 3.9±0.96 4.9±0.10 0.63±0.03
F21 108.12±0.70 3.8±0.50 4.8±0.12 0.66±0.03
F22 111.45±0.80 3.7±0.63 4.5±0.10 0.52±0.015
F23 110.23±0.55 3.7±0.78 4.9±0.17 0.56±0.04
F24 110.12±0.60 3.8±0.86 4.9±0.14 0.53±0.06
F25 109.14±0.75 3.7±0.57 4.7±0.15 0.57±0.07
F26 110.18±0.15 3.9±0.63 4.9±0.18 0.52±0.03
F27 111.23±0.75 3.9±0.98 5.3±0.05 0.59±0.04
*Values are expressed in mean± SD :( n=20)
#Values are expressed in mean± SD :( n=3)

In vitro Dissolution Studies:

100

90

F1
80
F2
F3
70
F4
F5
Cumulative % Drug Released

F6
60 F7

50

40

30

20

10

0
0 1 2 3 4 5 6 7 8
Time (Hours)

Figure 4: In vitro Drug Release Profile for colon ivermectin tablets F1-F7

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Figure 5: In vitro drug relase profile for colon ivermectin tablets f8-f14

Figure 6: In vitro Drug Release Profile for colon ivermectin tablets F15-F21

100

90

F22
80
F23
F24
70
F25
F26
Cumulative % Drug Released

F27
60

50

40

30

20

10

0
0 2 4 6 8
Time (Hours)

Figure 7: In vitro Drug Release Profile for colon ivermectin tablets F22-F27

In vitro drug release studies intestinal fluid pH 6.8 and simulated colonic fluid
(SCF) pH 7.4.
In vitro release profiles of ivermectin was
The formulation with drug superdisintegrants
sequentially determined in0.1 N HCL pH 1.2,
ratio F17 was selected as optimized formulation

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because it showed a maximize release in proximal colon.

Table: Comparison of marketed product with optimized formulation (F17)

Figure 8: Comparative In vitro study plot of optimized formulation (F17) and conventional marketed
tablet

Mathematical modeling of optimized formula water- soluble drug the self-erosion of the matrix
of ivermectin colon tablets will be the principal relese mechanism. To
In vitro dissolution has been recognised as an accomplish these studies the cumulative profiles of
important element in drug development. Under dissolved drug are more commonly used in
certain conditions it can be used as a surrogate for opposition to their differential
the assessment of bioequivalence.There are several profiles.Mathematical modeling of the relese
models to represent the drug dissoluton profiles kinetics of specific classes of controlled-relese
where ft is a function of time releated to the amout systems may be used to predict solute release rates
of drug dissolved from the pharmaceutical dosage from and solute diffusion behavior through
systems.The quatitative interpretation of the values polymers and elucidate the physical mechanisms of
obtained in the dissolution assay is facilitated by solute transport by simply comparing the relese
the usage of a generic eqation that mathematically data to mathematical models.
translates the dissolution curve in the function of In the view of establishment of release
some parameters releated with the pharmaceutical mechanism and quatitatively interpreting and
dosage forms. translate mathematically the dissolution date being
A water soluble drug incorporated in a matrix is plotted.
mainly released by diffusion, while for a low

In vitro drug release order kinetics for optimized (F17) Formulation

Table 9: Release kinetics of optimized formulation of ivermectin colon tablets
Formulation Code Zero Order First Order Higuchi Korsmeyer-Peppas

R2 n R2 n R2 n R2 n
F17 0.994 8.02 0.842 0.119 0.946 29.41 0.988 0.817

From the above results it is apparent that the of zero order plot i.e.0.994 indicates that the drug
regression coefficient value closer to unity in case release follows a zero order mechanism (Table 9).

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This data indicates a lesser amount of linearity configuring the data in to various mathematical
when plotted by the first order equation. Hence it modeling such as Higuchi and Korsmeyer-Peppas
can be concluded that the major mechanism of drug plots. Further the n value obtained from the
release follows zero order kinetics. Korsmeyer-Peppas plots i.e. 0.817 indicating non
Further, the translation of the data from the Fickian (anomalous) transport thus it projected that
dissolution studies suggested possibility of delivered its active ingredient by coupled diffusion
understanding the mechanism of drug release by and erosion.

In vitro drug release order kinetics for marketed product

Table 10: Release kinetics of Marketed Product
Formulation Code Zero Order First Order Higuchi Korsmeyer-Peppas

R2 n R2 n R2 n R2 n

Marketed 0.923 4.87 0.967 0.088 0.925 27.05 0.945 0.823

From the above results it is apparent that the understanding the mechanism of drug release by
regression coefficient value closer to unity in case configuring the data in to various mathematical
of First order plot i.e.0.967 indicates that the drug modeling such as Higuchi and Korsmeyer-Peppas
release follows a first order mechanism (Table No plots.
10). This data indicates a lesser amount of linearity Further the n value obtained from the
when plotted by the zero order equation. Hence it Korsemeyer-Peppas plots i.e. 0.823 indicating non
can be concluded that the major mechanism of drug Fickian (anomalous) transport thus it projected that
release follows first order kinetics. delivered its active ingredient by coupled diffusion
Further, the translation of the data from the and erosion.
dissolution studies suggested possibility of

Correlation Coefficient Values For Optimized

Table 11: Regression coefficient (R 2) & n values
S. No Formulation Zero order First order Higuchi Korsmeyer-Peppas model n
model
1 F17 0.994 0.847 0.956 0.988 0.817
2 Marketed 0.923 0.967 0.925 0.945 0.823

The in vitro drug release profiles were fitted to (anomalous) transport thus it projected that
several kinetic models and release data followed by delivered its active ingredient by coupled diffusion
their R2 and n values shown in the Table 11/ The and erosion. The marketed conventional
optimized formulation was best fitted in Zero Order formulation followed the first order kinetics
and Korsmeyer-Peppas. The optimized formulation indicating drug release is directly proportional to
n value was 0.817 indicating non Fickian the concentration of drug.

Stability study
Table 12: Parameters after Accelerated Stability Study of Formulation F17

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Temperature Maintained at 40 ±20C ;

Relative Humidity (RH) Maintained at 75%±5%RH
Parameters
Initial After 1 month After 2 months After 3 months
Drug Content (%) 99.94±0.14 99.83±0.68 99.70±0.37 99.62±0.22
In Vitro Drug Release (%) 98.21±1.15 98.17±1.53 98.15±1.42 98.11±1.35
Disintegration tests 37±0.64 37±0.56 36±0.67 36 ±0.23

Hardness 4.7±0.84 4.7±0.34 4.7±0.25 4.7±0.13

There were no physical changes in appearance varying proportions of natural superdisintegrants

and flexibility. After subjecting the optimized by direct compression method and all formulations
formulation (F17) to the Accelerated Stability were coated by Eudragit RS 100 coating solution
Studies, the results were shown that there were no which is a pH sensitive polymer to prevent drug
major changes in Drug Content, In Vitro Drug release in stomach and intestine. Entire drug will
Release, Disintegration tests and Hardness. Hence release in proximal part of colon. The formulation
the formulation was found to be stable. F17 was selected as optimized formulation because
it showed minimum release in stomach and small
intestine and a maximize release in proximal colon.
SUMMARY AND CONCLUSION In vitro drug release studies were carried out to
In present work attempt was made to formulate know the drug release with respective of the time.
and evaluate colon tablets of ivermectin. Attempts Maximum drug was released from the formulation
were made to achieve immediate drug release from F17 within 7 Hrs. Based on the physico-chemical
the dosage form. Twenty seven formulations (F1- properties and in vitro drug release, the formulation
F27) were prepared by direct compression method F17 was concluded as the best formulation. No
using 3 3 Response surface method where 3 3 prominent changes in physico-chemical properties
indicates 3 variables and 3 levels of natural of formulation after its exposure to accelerated
superdisintegrants like Gellan Gum, Locust bean conditions of temperature (40±2 0C) and humidity
Gum and Fenugreek seed Gum (low, middle and conditions (75 ± 5%RH) were seen. Hence the
high concentrations) by using Design of experiment developed formulation was found to be stable even
software. In the Preformulation properties was after subjecting to accelerated stability conditions.
carried out and the values obtained were within the In the present work, it can be concluded that the
range. And FTIR studies results revealed that there colon Tablets of ivermectin formulations can be an
was no incompatibility between drug and innovative and promising approach for the delivery
excipients. Thus, colon Tablets were formulated by of ivermectin for the treatment of worm infections.

REFERENCES
[1]. Barbara L, Teresa C, Federica B, Isabella O, Z: pH-sensitive polymeric physical-mixture for possible
site-specific delivery of ibuprofen. Eur J Pharm Biopharm 55, 2003, 199-202.
[2]. Lachman L, Lieberman HA, Kanig JL: The theory and practice of industrial pharmacy. Bombay,
Varghese publishing house: Hind Rajasthan building; 3, 1991, 293.
[3]. Antonin KH, Rak R, Beick PR, Schenker U, Hastewell J, Fox R: The absorption of human calcitonin
from the transverse colon of man. Int J Pharm.130, 1996, 33-39.
[4]. Van-den GM, Kinget R: Oral colon-specific drug delivery: a review. Drug Delivery 2, 1995, 81-93.
[5]. Rama Prasad Y, Krishnaiah Y, Satyanarayana S: In vitro evaluation of guar gum as a carrier for colon -
specific drug delivery. J Controlled Release 51, 1998, 281-287.
[6]. Jain NK: Advances in Controlled and novel Drug Delivery. New Delhi, Cbs publisher and distributors; 1,
2008, 86-90.

www.ijpir.com
 110
Shirisha B et al., Int. J. Pharm & Ind. Res., Vol.–06 (04) 2016 [98-110]

[7]. Rama Prasad Y, Krishnaiah Y, Satyanarayana S: In vitro evaluation of guar gum as a carrier for colon -
specific drug delivery. J Controlled Release 51, 1998, 281-287
[8]. Xinmuing Liu, Qingshen Sun, Huajie Wang, Lei Zhang, Jin-Ye Wang, Microspheres of Corn protein,
zein, for an ivermectin drug delivery system Biomaterials, 26, 2005, 109- 115.
[9]. Klaus Florey, David.W.F, Analytical Profiles of Drug Substances- Ivermectin, Academic Press-Elsevier,
New Delhi; 17, 2005, 156-184.
[10]. Pragnesh patel, anupkumar Roy. Formulation and evaluation of colon targeted tablets of Ornidazole for
the treatment of amoebiasis, International journal of drug delivery & research. 3(1), 2011, 52-61.
[11]. Krishnaiah YSR, Satyanarayana V, Rama Prasad YV. Studies of guar gum compression -coated 5-
aminosalicylic acid tablets for colon-specific drug delivery, Journal of Drug Development and Industrial
Pharmacy. 25, 1999, 651– 657.
[12]. Montgomery, Douglas C, Design and Analysis of Experiments: Response surface method and designs,
John Wiley and Sons, Inc. New Jersey, 2005, 210-256.
[13]. Schwartz BJ,Connor RE, Optimization technique in pharmaceutical formulations and processing, J
Drugs Pharm Sci Modern Pharm, 72, 1996, 727-54.
[14]. Nair Rahul, Sevukarajan.M, Vishnu Priya K, Arun Kumar K.S, Response Surface Methodology for the
Optimization OF Ethylcellulose Microspheres, International Journal of PharmTech Research, 3 (2), 775-
783.
[15]. Friend DR, Phillips S, McLeod A, Tozer TN. Relative anti inflammatory effect of oral dexamathasoneß -
D-glucoside and dexamathasone in experimental inflammatory bowel disease. J Pharm Pharmacol. 43,
1991, 353–355.
[16]. Fukui E, Miyamura N, Uemura K, Kobayashi M. Preparation of enteric coated timed release press-coated
tablets and evaluation of their function by in vitro and in vivo tests for colon targeting. Int J Pharm. 204 ,
2000, 7 - 15.
[17]. Gardner N. Haresign W, Spiller R, Faraj N, Wiseman J, Norbury H, Illum L. Development and validation
of a pig model for colon-specific drug delivery. J Pharm Pharmacol. 48, 1996, 689–693.
[18]. Gazzaniga A, Bussetti C, Moro L, Sangali ME, Giordano F. Time dependent oral delivery system for
colon targeting. STP Pharm Sci. 5, 1995, 83-88.
[19]. Raosaheb s. shendge, Fatima j. sayyad. Development of colon specific drug delivery of aceclofenac by
using effective binder system of ethyl cellulose, International Journal of Biomedical and Pharmaceutical
Sciences. 3, 2010, 1-5.

www.ijpir.com