Sie sind auf Seite 1von 16

IAJPS 2017, 4 (04), 910- 925 Dhananjay M.

Patil et al ISSN 2349-7750

CODEN (USA): IAJPBB ISSN: 2349-7750

INDO AMERICAN JOURNAL OF


PHARMACEUTICAL SCIENCES
http://doi.org/10.5281/zenodo.556750

Available online at: http://www.iajps.com Research Article

FORMULATION DEVELOPMENT AND EVALUATION OF


ORODISPERSIBLE TABLET OF CINNARIZINE SOLID
DISPERSION
Dhananjay M. Patil*, Kaveri R. Wagh, Sapna S. Chaudhari, Vinod A. Bairagi,
Valmik R Patil
Department of Pharmaceutics-K.B.H.S.S Institute of Pharmacy, Malegaon, Nasik-423203.
Received: 11 April 2017 Accepted: 20 April 2017
Abstract:
The objective of present study was to formulate directly compressible orodispersible tablets of Cinnarizine with
improved solubility and bioavailability by using solid dispersion technique. Cinnarizine is a H1 receptor
antagonist and widely used in the treatment of motion sickness, vomiting and vertigo disorder. Solid dispersion
of Cinnarizine was prepared by Solvent evaporation method and physical mixture using novel polymer soluplus
as carrier. 1:1, 1:2 and 1:3 these three different weight ratios of drug and carrier respectively were taken.
Saturation solubility of drug was determined in physical mixture and solid dispersion formulation. The prepared
solid dispersion formulations were further characterized by drug contents, FTIR spectroscopy, DSC and in-vitro
drug release. From that crystalline form of Cinnarizine is converted into amorphous state during formulation of
solid dispersion. Solid dispersion by solvent evaporation method in 1:3 ratios showed better results than other
formulations. Orodispersible tablets of Cinnarizine were compressed using selected solid dispersion 1:3
formulation and excipients with kyron T 314 as a superdisintegrant. Orodispersible tablet shows disintegration
time 13 seconds and in-vitro drug release 99.75 %, which is better as compare to marketed conventional tablet
66.92 % within 15 minutes. Thus formulation of orodispersible tablet of Cinnarizine solid dispersion showed
increased solubility and bioavailability with patient complies and convenience.
Keywords: Cinnarizine, Soluplus, Kyron T-314, Solid dispersion, Orodispersible tablet, Solubility.
Corresponding author:
Dhananjay M. patil, QR code
Department Of Pharmaceutics,
K.B.H.S.S Trust Institute of Pharmacy
Bhaygoan Road Opp, Jajuwadi Malegoan Camp,
Nasik-423203,
Email-drdhananjaypatil@hotmail.com
Mob No-09823385304

Please cite this article in press as Dhananjay M. patil et al, Formulation Development and Evaluation of
Orodispersible Tablet of Cinnarizine Solid Dispersion, Indo Am. J. P. Sci, 2017; 4(04).

www.iajps.com Page 910


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

INTRODUCTION: antagonist of T-type voltage-operated calcium ion


Limited and variable drug absorption resulting in channels, because its binding blocks the channels
poor bioavailability is the major problem that can and keeps them inert. In treatment of nausea
be encountered when delivering an active agent via motion sickness and vertigo Cinnarizine exerts its
oral route. Bioavailability of the drug is one critical effects by inhibiting the calcium currents in voltage
parameter for determining the efficacy of gated channels in type II vestibular hair cells within
pharmaceutical formulations[1-2]. Drug absorption the inner ear. Cinnarizine is BCS class II drug
from GIT can be limited and varied by a variety of (Low solubility and high permeability). Cinnarizine
factors with most significant contributors being is practically insoluble in water, low and invariably
poor aqueous solubility and/or membrane bioavailability and thus delays onset of action. It is
permeability of the drug molecule. The well established fact that, dissolution is the rate
therapeutically effective amount of a medicine in a limiting step in the absorption process.
composition should be made available to the Consequently, numerous attempts have been made
organism, with optimum blood concentrations of to modify the dissolution characteristics of
the active ingredients reached within the shortest insoluble drugs in an attempt to attain fast and
possible time. Since the development cost of a new more complete dissolution[10,11]. In an attempt to
chemical entity is very high, the pharmaceutical enhance the solubility, dissolution rate and
companies are focusing on the development of new bioavailability of slightly soluble drugs, solid
drug delivery systems for existing drug with an dispersion by using novel polymer soluplus has
improved efficacy and bioavailability together with been extensively applicable.
reduced dosing frequency to minimize side Many patients find it difficult to swallow tablets
effects[3-5]. Solubility enhancement of poorly and hard gelatin capsules and thus not comply with
water soluble drugs are needed. Solid dispersion prescription that results in high incidence of non-
technique is extensively used to increase the compliance and ineffective therapy. Orodispersible
solubility of poorly soluble drug [6]. tablets are gaining prominence as new drug
For the past two decades, there has been enhanced delivery systems. These dosage forms dissolves or
demand for more patient compliance dosage disintegrate in oral cavity within a minute without
forms. As a result, the demand for their the need of water or chewing before
technologies has been increasing three-fold swallowing[12]. Kyron T-314 is used as
annually. Solid dosage forms like tablets and superdisintegrant in given formulation to achieve
capsules are more popular and preferred drug fast disintegration of tablet and patient compliance
delivery system because they have, accurate and convenience[13].
dosing, good physical and chemical stability. But
the most evident drawback of the commonly used MATERIALS AND METHODS:
oral dosage forms like tablets and capsules is Materials:
difficulty in swallowing, leading to patients Cinnarize and Soluplus were obtained as gift
incompliance particularly in case of pediatric and sample from Glenmark pharma Nasik, and BASF,
geriatric patients, but it also applies to people who The chemical company Germany respectively.
are ill in bed and to those active working patients Kyron T-314 was obtained as gift sample from
who are busy or traveling, especially those who Corel Pharma, Ahmadabad. All other ingredients
have no access to water[7]. are of pharmaceutical and analytical grades.
Difficulty in swallowing (dysphasia) is a common
problem of all age groups, especially the elderly Methods:
and pediatrics, because of physiological changes Preparation of solid dispersion of Cinnarizine
associated with these groups[8,9]. Other categories with Soluplus:
that experience problems in using conventional oral Preparation of physical mixtures (PMs):
dosage forms include the mentally ill, The physical mixtures were prepared by mixing the
uncooperative and patients suffering from required amount of Cinnarizine and Soluplus in the
nausea, motion sickness, sudden episodes of ratio of 1:1, 1:2, 1:3 for 15 min in a mortar with
allergic attack or coughing. It is estimated that pestle until a homogeneous mixture was obtained.
35-50% of the population is affected by this This resulting mixture was sieved through a 40
problems. Recent advances in Novel Drug mesh screen. The powder was stored in a dessicator
Delivery Systems aim to enhance safety and until further evaluation.
efficacy of drug molecule by formulating a
convenient dosage form for administration and to Preparation solvent evaporation method
achieve better patient compliance. One such dispersions (SDs)[14]:
approach is to enhance the solubility of drug by Accurately weighed quantities of Cinnarizine and
solid dispersion technique and further to formulate Soluplus in the ratio of 1:1 1:2, 1:3 by weight were
orodispersible tablet[9]. dissolved in acetone in a porcelain dish. The
Cinnarizine is a piperazine derivative, H1 receptor solvent was evaporated by occasional stirring and
antagonist. Cinnarizine is classified as a selective wet mass was kept in hot air oven at 50oC for

www.iajps.com Page 911


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

drying. The dried mass was sieved through 40 Formulation of tablets using Solid dispersion of
mesh screen. The solid dispersion was stored in a Cinnarizine
dessicator until further evaluation. Tablets containing equivalent to 25 mg of
Cinnarizine solid dispersion were prepared by
Characterization of solid dispersion direct compression. The blend was compressed on
Saturation solubility studies[15]: a 10 station rotary machine using round shaped,
Excess quantity of pure Cinnarizine and its all concave punches. The composition of tablet is
prepared physical mixtures and solid dispersions given in following table.
with Soluplus were added in a 50 ml of glass Table 1: Composition of tablet
stoppered volumetric flasks containing 25 ml of Ingredients F1 F2 F3 F4
solvent (pH 1.2 buffer solution and phosphate
(mg) (mg) (mg) (mg)
buffer pH 6.8 separately). The flasks were sealed,
placed on mechanical shaker and agitated for 24 Solid Dispersion 100 100 100 100
hrs at 280C 0.20C. After 24 hrs, the samples were Kyron T 314 2 4 6 8
then filtered through Whatman filter paper, diluted Aspartame 1.2 1.2 1.2 1.2
suitably and absorbance was measured at 254 nm. Magnesium 0.6 0.6 0.6 0.6
stearate
Drug content [15]: Talc 0.6 0.6 0.6 0.6
The content of Cinnarizine in each physical
Microcrystalline 95.6 93.6 91.6 89.6
mixture and solid dispersions was determined using
cellulose pH 102
by UV spectroscopy. Accurately weighed physical
mixture or solid dispersion equivalent to 25 mg of Total 200 200 200 200
Cinnarizine was transferred to 100 ml volumetric
flask containing 10 ml of methanol and dissolved. Evaluation
The volume was made up to 100 ml with methanol. Physical evaluation of tablet blend
The solution was filter through Whatman filter Angle of repose[19]:
paper. 1 ml of this solution was diluted 10 times The angle of repose of each powder blend was
with methanol to achieve 25 g/ml and the determined by glass funnel method by using the
absorbance was measured at 254 nm. following equation
tan = h/r
Infrared spectroscopy[16,17]: Where,
IR spectra were obtained by KBr disk method h = height of cone
using Fourier- transform infrared (FTIR) r = radius of powder cone
spectrometer (8400 S Shimadzu). KBr disks
prepared using hydrostatic press a thrust of 5 Bulk density[19]:
tons/cm2 for 5 min. The scanning range was 400 to Bulk density of solid dispersion granules were
4000 cm-1. determined by pouring gently 25 gm of sample
through a glass funnel into a 100 ml graduated
Differential scanning calorimetry[16,17]: cylinder. The powder was carefully leveled without
The DSC measurements were performed on a compacting it and the apparent volume was
Differential Scanning Calorimetry (Shimadzu-DSC measured (Vo). Bulk density was calculated as
60) with a thermal analyzer. All accurately below-
weighed samples (5 mg) were placed in sealed Bulk density = M/Vo
aluminum pans, before heating under nitrogen flow Where,
(10 ml/min) at a scanning rate of 10C/min. from M = mass of powder
35C- 300C. An empty aluminum pan was used as Vo = apparent unstirred volume
reference.

Dissolution studies[15,18]: Tapped density[19]:


The pure drug, physical mixtures and solid The tapped density was determined by pouring 25
dispersions equivalent to 25 mg of Cinnarizine gm sample (solid dispersion with excipients)
were subjected to the dissolution study using USP through a glass funnel into a 100 ml graduated
dissolution apparatus type II (Paddle) maintained at cylinder. The cylinder was tapped from height of 2
37 0.5oC and 50 rpm. Dissolution medium used is inches until a constant volume obtained. Volume
pH 1.2 buffer 900ml. occupied by the sample after tapping was recorded
Samples of 5 ml were withdrawn at regular interval and tapped density was calculated.
of 3 min. The volume withdrawn was replaced by
fresh volume of dissolution medium to maintain
constant volume of medium. The filtered samples Carrs index[19]:
were analyzed spectrophotometrically at 254 nm. It is also one of the simple method to evaluate flow
property of a powder by comparing the bulk

www.iajps.com Page 912


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

density and tapped density. Carrs index is also In-vitro disintegration study[18,20]:
known compressibility index and which was The process of breakdown of a tablet into smaller
calculated. particles is called as disintegration.
The in-vitro disintegration time of a tablet was
determined using disintegration test apparatus. The
disintegration test was carried out using USP
disintegration test apparatus-II. Tablets were placed
Hausners ratio[19]: individually in each tube of disintegration test
It provides an indication of the degree of apparatus and discs were placed over each tablet.
densification that could result from vibration of Distilled water (900 ml) was used as the medium
feed hopper. Lower the hausner ratio better is the which is maintained at 37 2C and the time taken
flowability. for each tablet to disintegrate completely was
Tapped density recorded.
Hausner ratio
Bulk density Hardness[20]:
Evaluation of tablets Tablet hardness and resistance to powder and
The tablets were evaluated for the following test friability are necessary requisites for acceptance.
parameters, The Pfizer hardness tester was used for hardness
testing. Generally 4 kg/cm2 hardness is considered
Weight variation test[18]: as acceptable for uncoated tablets.
Twenty tablets of each formulation were weighed
individually using an electronic balance. The Wetting time[21,22]:
average weight was calculated and individual tablet A piece of tissue paper folded twice was kept in
was compared with the average value and the petri dish (internal diameter 5.5 cm) containing 10
deviation was recovered. ml of distilled water. A tablet having a small
amount of amaranth powder on the upper surface
Content uniformity of tablets[15]: was placed on the tissue paper. The time required
Ten tablets were weighed and crushed in a small to develop a red color on the upper surface of the
mortar. The fine powder equivalent to 25 mg of tablet was recorded as wetting time.
Cinnarizine was transferred to 100 ml volumetric
flask containing 10 ml of methanol and dissolved. Water absorption ratio[21,22]:
The volume was made up to 100 ml with methanol. A piece of tissue paper folded twice was placed in
The solution was filter through Whatman filter a small Petri dish (5 cm diameter) containing 6 ml
paper. 1 ml of this solution was diluted 10 times of water. A tablet was put on the tissue paper and
with methanol to achieve 25 g/ml and the allowed to wet completely. The wetted tablet was
absorbance was measured at 254 nm. then weighed and the water absorption ratio R
was determined by using following equation.
Thickness:
Twenty tablets were randomly selected from R = Wb - Wa x 100
formulations and thickness was measured Wa
individually. It was expressed in millimeter and Where,
average was calculated. Wa= weight of tablet before water absorption
Wb = weight of tablet after water absorption.
Friability test[18]:
Friability test is performed to assess the effect of In-vitro dispersion time[23]:
friction and shocks, which may often cause tablet to In-vitro dispersion time of prepared tablet was done
chip, cap or break. Roche friabilator was used for the by dropping the tablet in 10 ml measuring cylinder
purpose. (according to USP monograph 1216 - containing 6 ml of simulated salivary fluid (pH
tablets with a unit weight equal to or less than 650 6.8). Time required for complete dispersion of
mg, take a sample of whole tablets corresponding as tablet was measured.
near as possible to 6.5 gm.) Pre weighed sample of
tablets was placed in the friabilator, which was then
operated for 100 revolutions/min. Tablets were Dissolution study[18]:
dusted and reweighed. The percentage friability was In order to study prepared tablet subjected to the
calculated by, dissolution study using USP dissolution apparatus
type II (Paddle) maintained at 37 0.5oC and 50
W initial W final rpm. Dissolution medium used is pH 1.2 buffer
F= ------------------- 100 900ml. Samples of 5 ml were withdrawn at regular
W final interval of 3 min. The volume withdrawn was
Percentage weight loss was calculated. A loss of replaced by fresh volume of dissolution medium to
less than 0.5 to 1 % in weight was generally maintain constant volume of medium. The filtered
acceptable.

www.iajps.com Page 913


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

samples were analyzed spectrophotometrically at drug content, and in-vitro dissolution were
254 nm. evaluated according to the procedure described as
above.
Stability studies[24]: RESULTS AND DISCUSSIONS:
In the present study, the stability studies were Characterization of solid dispersion system
carried out as per ICH guidelines at 40C 2C/75 Saturation solubility studies:
% 5% RH for the selected formulation (F4) for 3
month. After specified time intervals, parameters
like hardness, dispersion time, disintegration time,

Table.2: Saturation solubility of PD (Cinnarizine), PMs and SDs in pH 1.2 buffer

Formulation code Saturation Solubility(mg/ml)


PD 0.632611.51
PM1:1 1.57651.79
PM1:2 2.3511.74
PM1:3 2.83520.658
SD1:1 3.700141.31
SD1:2 3.993241.084
SD1:3 4.846061.08

Mean, SD, n= 3

Fig 1: Saturation solubility of PD, PMs and SDs in pH 1.2 buffer

Table 3: Saturation solubility of PD, PMs and SDs in pH 6.8 phosphate buffer

Formulation Code Saturation Solubility(mg/ml)


PD 0.0039750.135
PM1:1 0.006720.3400
PM1:2 0.0099630.2064
PM1:3 0.0156390.4745
SD1:1 0.0205490.2064
SD1:2 0.0287930.3400
SD1:3 0.030684 0.2813

Mean, SD, n= 3

www.iajps.com Page 914


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Fig 2: Saturation solubility of PD, PMs and SDs in pH 6.8 phosphate buffer
The saturation solubility profile for the pure Table 4: Results of drug content with Soluplus.
Cinnarizine and its all prepared physical mixture
and solid dispersion is shown in figure no.6.5 and Methods Drug Content Ratio
6.6. These figures indicate that Cinnarizine is (%)
having very low solubility i.e. 0.6326 mg/ml and Physical Method 1:1 98.78.8050
0.0039 mg/ml in pH 1.2 buffer solution and pH 6.8 (PMs) 1:2 99.19.8798
phosphate buffer respectively. Physical mixture 1:3 99.20.9814
and solid dispersion with Soluplus shows increase Solvent 1:1 99.23.3098
in solubility respectively as concentration of Evaporation 1:2 99.13.9226
polymer is increases. Method (SDs) 1:3 100.04.4000
The ratio 1:3 of solid dispersion gives the Mean, SD, n= 3
maximum saturation solubility among all the The drug content of Cinnarizine physical mixtures
physical mixture and solid dispersions i.e. 4.8460 and solid dispersions was found to be in range
mg/ml and 0.030684 mg/ml in pH 1.2 buffer 98.78 % to 100.04 % and these values are within
solutions and pH 6.8 phosphate buffer respectively. the acceptable range. Low values of standard
Analysis of drug content deviation with respect to drug content indicate
The percentage drug content of PMs and SDs are uniformity of drug distribution in all the physical
shown in table no 4. mixtures and solid dispersions of Cinnarizine.

30

%T

25

20
1029.92

15
1384.79
1596.95

1184.21

923.84
1371.29

10
1357.79

864.05
1076.21
2690.51

1305.72
2864.09

1278.72

1004.84

5
3022.25
2956.67

1490.87

964.34
1141.78
1448.44
2767.66
2810.09

4000 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600
sample 1 1/cm

Fig .3: FTIR spectrum of Cinnarizine

14
%T
12

10
2156.27

8
2474.50

717.47

6
840.91
946.98

4
973.99
1024.13
1112.85
1197.71

2
1375.15
1481.23
1438.80

1242.07
1627.81
1739.67
2858.31
3537.20

2929.67

3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800
sample 2 1/cm

Fig 4: FTIR spectrum of Soluplus

www.iajps.com Page 915


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

45

%T

37.5

642.25
1868.89
1959.54
30

794.62
837.05
923.84
864.05
2362.64

1029.92
22.5

1336.58

1197.71

1076.21
3056.96

999.06
1371.29
3022.25

740.61
15

2864.09

1265.22
1490.87

964.34
1733.89
2958.60

1141.78
1635.52
2767.66

1448.44
7.5

2810.09
0

3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800
sample 5 1/cm

Fig 5: FTIR spectra of solid dispersion (1:3)

Fig 6: FTIR spectra of Kyron T-314

Fig 7: FTIR spectrum of orodispersible tablet (F4)


Fourier Transform Infra Red (FTIR) aliphatic C-H stretching occurs at 2956.67 cm-1, the
Spectroscopy: C=C stretching occurs at 1490.87 cm-1, C-N
Fourier transform infrared spectroscopy has been stretching occurs at 1141.78 cm-1. Soluplus shows
used to assess the interaction between carrier and the characteristic peaks O-H stretching at 3537.20
drug molecule. The FTIR spectrum of Cinnarizine, cm-1 , C-H stretching at 2929.67 cm-1 C=O
Soluplus and solid dispersion prepared by solvent stretching at 1627.81 cm-1, C-N at C-N stretching
evaporation method are as shown in figure no.6&7. 1197.71 cm-1 The peaks of solid dispersion of
Cinnarizine with Soluplus shows one additional
The FTIR studies were performed to detect the peak at 3537.20 cm-1 indicative of intermolecular
molecular interaction between drug and polymers. hydrogen bonding between Cinnarizine and
The FTIR spectra of Cinnarizine, Soluplus and Soluplus.
their solid dispersion are shown in the figure no. 3, The IR spectra of Kyron T 314the characteristic
4 and 5 respectively. In FTIR spectra of peak C=C stretching occur at 1480.34 cm-1 , C-H
Cinnarizine the characteristic absorption peaks, stretching occur at 2870 cm-1, and CH 2 bending
aromatic C-H bending occurs at 3022.25 cm-1, occur at 1465.45 cm-1. The IR spectra of F4

www.iajps.com Page 916


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

formulation blend show all characteristic peaks Differential scanning calorimetry study
Cinnarizine and solid dispersion and it indicates The DSC thermo gram of Cinna rizine, Soluplus,
that there is no interaction between solid dispersion solid dispersion prepared by solvent evaporation
and Kyron T 314. method and its overlapped as shown in figure
no.8-11 respectively

DSC T hermal Analysis Result of Cinnarizine


mW

0.00
Onset 0
25. 32x
C10
0
Endset 0
-104. 72x
C10 Peak 121.27x
C10
Onset 0
118.39x
C10
Trans it ion 0
1.50x
mW10
0 Endset 0
125.34x
C10
0.30x
mW10 / m g
0
Mid Point 0
25. 03x
C10 Heat -347. 58x
mJ10
-5.00 0
Height -13. 67x
mW10

-10.00

50.00 100.00
Temp [C]

Fig 8: DSC Thermogram of Cinnarizine

DSC T hermal Analysis Result of Soluplus


mW

-1.00

Onset 0
34. 28x
C10
-2.00 Endset 0
41. 93x
C10
0
Trans it ion 0.01x
mW10
0
0.00x
mW10 / m g
0
-3.00 Mid Point 36. 19x
C10
Peak 0
81. 03x
C10
0
Onset 72. 00x
C10
0
Endset 87. 91x
C10
-4.00 Heat 0
-31. 36x
mJ10
Height 0
-0. 48x
mW10

-5.00

-6.00
40.00 60.00 80.00 100.00
T emp [C]

Fig 9: DSC Thermogram of Soluplus

D SC Thermal Analysis Result of Cinnarizine-soluplus(solid dispersion1:3)


mW
0. 00

-2. 00
0
Peak 93.48x
C 10
Onset 0
87.77x
C 10
Endset 0
99.91x
C 10
-4. 00 H eat - 19.090
x10
mJ
0
Onset 38.13x
C 10 0
H eig ht - 0.40x
mW10
0
Endset 46.34x
C 10 Peak 0
115.95x
C 10
Tr ansition 0
0.73x
mW10 0
Onset 111.29x
C 10
0
0.15x
mW/mg
10 0
-6. 00 Endset 119.34x
C 10
M id Point 0
47.59x
C 10 H eat - 246.410
x10
mJ
H eig ht 0
- 7.82x
mW10

-8. 00

D SC

50.00 100. 00 150. 00


Tem p [C]

Fig 10: DSC Thermogram of solid dispersion (1:3)

www.iajps.com Page 917


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

D SC Thermal Analysis Result of Cinnarizine-soluplus 1:3 (Overlapped)


mW

0. 00

Onset 0
38.93x
C 10
-5. 00 0 Peak 0
115.95x
C 10
Endset 46.24x
C 10
0
Onset 111.26x
C 10 0
Tr ansition 0
0.64x
mW10 Peak 121.27x
C 10
0 Endset 0
119.39x
C 10
0.13x
mW/mg
10 Onset 0
118.36x
C 10
M id Point 0
46.47x
C 10 H eat - 241.310
x10
mJ 0
Endset 125.18x
C 10
H eig ht - 7.770
x10
mW
H eat - 344.210
x10
mJ
-10. 00 H eig ht - 13.630
x10
mW

M ixtur e D SC
C innar izine DSC

50.00 100. 00 150. 00


Tem p [ C ]

Fig 11: DSC Thermogram of Cinnarizine and solid dispersion (1:3) overlapped
From the figure no.8 the Cinnarizine showed the dissolution apparatus at 50 rpm in 900 ml pH 1.2
melting point at 121C, from figure no.9 Soluplus buffer solution as a dissolution medium.
showed the melting point at 81C, from figure Temperature of dissolution medium was
no.10 the solid dispersion showed the melting point maintained at 37 0.50C. PD 25 mg and PMs and
reduced to 115C from 121C and the intensity of SDs equivalent to 25 mg of Cinnarizine were added
the peak in pure drug is reduced. From the figure in each vessels. 5ml sample withdrawn at regular
no.11 it can be concluded that there is a formation time interval of 3 min and filtered through
of solid dispersion with conversion of drug Whatman filter paper. An equal volume of fresh
crystalline to amorphous form. dissolution medium was added in order to kept
total volume of dissolution medium constant.
Dissolution study Filtered samples absorbance was measured at 254
In order to investigate the release rate of PD, PMs nm and results are shown in table no 5-6and figure
and SDs with Soluplus in the ratio 1:1, 1:2 and 1:3 no12-13.
were subjected to dissolution study in USP type II
Table 5: Results of percentage cumulative drug release of PD, PMs with Soluplus
Time (min) PD PM 1:1 PM 1:2 PM 1:3
0 0 0 0 0
3 10.5460.5339 10.72230.1555 11.44650.3905 12.63610.4741
6 14.81640.4123 16.93710.3236 18.59630.4970 19.99940.3558
12 17.03590.8688 20.72690.4764 23.53030.5437 26.80150.3210
15 20.90660.6491 26.01061.1239 28.31720.8966 32.58631.118
18 25.78010.5563 33.55020.7962 34.85590.4669 38.66621.1249
21 31.14030.4715 39.73430.3302 40.68320.7665 44.66821.1813
24 35.91840.0784 44.86561.655 47.14131.5349 52.05031.2690
27 44.60761.005 55.53061.312 60.56881.1986 67.45070.6648
30 49.4320.4227 61.02570.9124 66.66990.8894 75.91670.4513
Mean, SD, n= 3

Fig 12: In-vitro dissolution profile of PD and PMs with Soluplus

www.iajps.com Page 918


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Table 6: Results of percentage drug release of PD, SDs with Soluplus


Time (min) PD SD 1:1 SD 1:2 SD 1:3
0 0 0 0 0
3 10.54600.533 13.20910.268 21.73960.2687 26.34300.498
6 14.81640.412 20.36470.238 30.23960.5382 34.50661.092
9 17.03590.868 27.2740.544 38.85870.8584 45.01130.829
12 20.90660.649 33.26930.392 46.77990.9484 58.29400.689
15 31.14030.471 40.17640.698 58.62320.5696 72.47661.335
18 31.14030.471 47.2760.414 69.28960.2302 84.92601.235
21 35.91840.078 54.41390.235 79.59950.9607 96.97680.418
24 39.89050.454 61.27960.353 91.93301.0698 99.82960.399
27 44.60761.005 70.1990.564 98.89320.2632 -
30 49.43200.422 78.78340.366 - -

Mean, SD, n= 3

Fig 13: In-vitro dissolution profile of PD, SDs with Soluplus


From the table no.5 and figure no.12, it is observed dissolution medium and improved wetability of the
that the physical mixture of 1:3 shows the higher drug particles, significant reduction particle size
percent cumulative drug release after 30 min as during the formation of the solid dispersion and
compared to the other physical mixture of 1:1, 1:2 intrinsically higher rate of dissolution of the
ratio and pure drug. This is 75.9167 0.4513 % as selected soluble polymer, which could pull
compared to other physical mixture of 1:1, 1:2 ratio insoluble but finely mixed drug into the bulk of
and pure drug, which is 61.0257 0.9124 %, dissolution medium.
66.6699 0.8894 % and 49.43 0.4227 % The Cinnarizine solid dispersion prepared with
respectively after 30 min. Soluplus by solvent evaporation method in ratio 1:3
From the table no.6 and figure no.13, it is observed showed better percent cumulative drug release as
that the solid dispersion of 1:3 shows the higher compared to other solid dispersions, physical
percent cumulative drug release after 24 min as mixtures and pure drug. The percent cumulative
compared to the other solid dispersion of 1:1, 1:2 drug release rate of solid dispersion with ratio 1:3
ratio and pure drug. This is 99.82 0.3998 % as was 99.82 0.399 % in 24 min. and solid
compared to other solid dispersion of 1:1, 1:2 ratio dispersion 1:1, 1:2, physical mixture 1:1, 1:2, 1:3
and pure drug, which is 78.78 0.366 %, 98.89 and pure drug was 75.91 %, 98.89 %, 61.02 %,
0.2632 %, and 49.43 0.4227 % respectively after 66.66 %, 75.91 0.957 % and 49.43 0.422 % in
30 min. 30 min. in pH 1.2 buffer respectively. Among all
In order to investigate the drug release from the these formulation solid dispersion with 1:3 ratios is
prepared solid dispersion, in-vitro dissolution study best due to percent cumulative drug release that is
carried out in pH 1.2. The better dissolution 100.19 % in 24 min.
performance of solid dispersions was increased as From the results of dissolution studies, the solid
compared to the pure drug and physical mixture in dispersion with 1:3 ratio prepared by using
pH 1.2 in a particular time course. This may be Soluplus was selected for tablet formulation.
attributed to the higher solubility of Soluplus in

www.iajps.com Page 919


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Evaluation of solid dispersion tablet parameters to study the flow properties of granules
Pre compression evaluation of tablet blend. angle of repose, mean bulk density, mean tapped
Formulations ready for compression containing density, carrs index, hausners ratio as shown in
solid dispersion of Cinnarizine and various table no.7
excipients were subjected for pre-compression
Table 7: Evaluation of precompression parameters of orodispersible tablets containing Cinnarizine solid
dispersion.
Formulation Angle of Bulk Density Tapped Density Carrs Index Hausners
Code Repose(0) (g/cm2) (g/cm2) (%) Ratio
F1 25.1033 0.8048 0.9260 13.08 1.1506
0.9042 0.0108 0.0102 0.3592 0.0047
F2 24.73 0.8217 0.9460 13.14 1.1514
0.4430 0.0232 0.0180 0.7950 0.0104
F3 23.9733 0.7954 0.9158 13.04 1.1500
0.9957 0.0113 0.0135 0.2655 0.035
F4 23.7833 0.7997 0.9158 12.68 1.1452
1.008 0.0157 0.0134 0.5167 0.0067
Mean, SD, n= 3
Formulation design: Post compression parameters:
The present study was carried out to develop The tablets prepared by direct compression
orodispersible tablets of Cinnarizine solid technique were subjected for evaluation according
dispersion (1:3) in order to improve patient to various official specifications and other
compliance and also to prepare user-friendly parameters like shape and color, thickness,
formulations. In this case, four formulations of diameter, hardness, friability, weight variation, in-
orodispersible tablets were prepared by direct vitro disintegration time, wetting time, water
compression method using superdisintegrant Kyron absorption ratio, dispersion time, drug content and
T 314. The detailed composition of each in- vitro dissolution studies as shown in table no.8
formulation is given in the table no.1. to 10 and figure no.14.

Table 8: Evaluation of post compression parameters of orodispersible tablets containing Cinnarizine solid
dispersion.
Formulation Hardness Thickness Weight Drug
Code (kg/cm 2) (mm) Diameter Friability Variation Content
n=5 n=20 (mm) (%) (mg) (%)
n=20 n=20 n=3
F1 3.90 4.94 7.49 0.5616 199.7 99.10
0.100 0.0228 0.0058 1.1742 0.6100
F2 3.78 4.96 7.49 0.4117 200.25 99.44
0.0836 0.0329 0.0044 1.4823 0.5086
F3 3.84 4.94 7.5 0.4723 200.15 99.60
0.1341 0.0290 0.0064 1.3518 0.4000
F4 3.86 4.96 7.49 0.4419 200 99.81
0.1140 0.0372 0.0075 1.0760 3987

Table 9: Evaluation of post compression parameters of orodispersible tablets containing Cinnarizine solid
dispersion.
Formulation code Wetting time (sec) Dispersion time Water absorption Disintegration time
(sec) ratio (%) (sec)

F1 31.330.5773 34.330.01 88.160.7636 26.160.7527


F2 24.661.1547 28.330.04 90.000.5000 21.50.8366
F3 19.660.5773 23.330.01 90.831.0408 16.830.7527
F4 14.01.000 19.330.01 94.661.0408 130.8944
Mean, SD, n=3

www.iajps.com Page 920


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Dissolution study of formulated tablet min. The percent cumulative drug release rate of
The formulated tablets were subjected to formulation F1 was 99.14 0.4240 % in 24 min.
dissolution study in USP type II dissolution F2 was 99.49 0.4672 %in 21 min, 99.4461
apparatus at 50 rpm in 900 ml pH 1.2 buffer 0.2273 % in 18 min and F4 was 99.7582 0.6297
solution as a dissolution medium. Temperature of % in 15 min. Among all these formulations F4 is
dissolution medium was maintained at 37 0.50C. best due to percent cumulative drug release that is
Orodispersible tablet equivalent to 25 mg of 99.7582 % in 15 min.
Cinnarizine were added in each vessels. 5 ml From the results of dissolution studies, the
sample withdrawn at regular time interval of 3 min, formulation F4 is selected as a final formulation
filtered through Whatman filter paper. An equal and compared with marketed tablet.
volume of fresh dissolution medium was added in
order to kept total volume of dissolution medium
constant. Filtered samples absorbance was
measured at 254 nm and results are shown in table
no 10 and figure no14.
The orodispersible tablet containing Cinnarizine
solid dispersion prepared with Soluplus by solvent
evaporation method in ratio 1:3 showed better
percent cumulative drug release in less than 30

Table 10: Results of percentage cumulative drug release of orodispersible tablet formulations F1-F4
Mean, SD, n=3

Time (min) F1 F2 F3 F4
0 0 0 0 0
3 27.45250.2688 28.77410.3583 31.9810.4655 34.94650.3905
6 35.64790.4756 36.48590.2682 44.15860.7357 49.65230.2358
9 46.62620.2366 47.98430.6224 57.42830.4733 70.99950.4751
12 59.76270.9956 60.86960.3233 71.8480.4733 88.68551.013
15 73.07410.6237 76.11740.6058 84.75740.7862 99.75820.6297
18 86.40590.8609 88.0010.2340 99.44610.2273 -
21 96.60270.8748 99.4980.4672 - -
24 99.14750.4240 - - -

Fig 14: In-vitro dissolution profile of orodispersible tablet formulations F1-F4

www.iajps.com Page 921


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Comparison between marketed Cinnarizine tablet (conventional) and selected


formulation F4
Table 11: Comparative result of marketed Cinnarizine tablet and formulation F4
Parameter Marketed Tablet Formulation F4
Weight Variation(n=20) 198.211.5301 200.001.0760
Hardness (Kg/cm2)(n=5) 4.31 0.7524 3.86 0.1140
Wetting Time (Sec.) 176.20.231 14.0 1.000
Friability (%) 0.7525 0.4419
Disintegration Time (Sec.) 305.53.526 13.00 0.894
Drug Content (%) 97.720.2350 99.810.3987
Mean, SD, n=3
Table 12: Results of percentage cumulative drug release of marketed tablet and formulation F4
Time (min) Marketed Tablet Formulation F4
0 0 0
3 24.42930.2370 34.94650.3905
6 36.20290.6258 9.65230.2358
9 44.75161.0082 70.99950.4751
12 56.06731.3602 88.68551.013
15 66.92720.2321 99.75820.6297
Mean, SD, n=3

Fig 15: In-vitro dissolution profile of marketed tablet and formulation F4


Comparative results between marketed Cinnarizine formulation show better results than conventional
tablet (conventional) and formulation F4 are marketed Cinnarizine tablet.
reported in table no 11-12 and figure no 15. Mouth
dissolving tablet of Cinnarizine is not available in Stability study
market. Percent cumulative drug release of The physical appearance of the samples kept for
marketed formulation in 15 min was 66.9272 stability studies were checked each month and
0.2321 % and F4 formulation was 99.7582 found that there was no difference in the
0.6297 %. appearance.
From the comparative study between marketed
tablet and formulation F4, it was concluded that F4

www.iajps.com Page 922


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Table 13: Stability studies for orodispersible tablets (F4)


Parameter 40C 2C/75% 5% RH

30 Day 60 Day 90 Day

Hardness (Kg/cm 2) 3.89 0.4370 3.940.7590 4.930.2743

Dispersion time (sec) 19.630.4211 20.170.3871 20.180.1835

Disintegration time (sec.) 13.470.1457 13.641.3804 14.200.2752

Drug content (%) 99.440.2758 99.500.3620 98.980.1552

In-vitro Dissolution 99.320.5387 99.290.1575 98.920.1560

Mean, SD, n=3


After completion of three month stability study there was no any significance change occurred in formulation
F4.
SUMMARY AND CONCLUSION: 0.8050 % to 100.04 0.4000 % and these values
The enhancement of the oral bioavailability is are within the acceptable range. Low values of
currently one of the greatest challenge in the standard deviation with respect to drug content
development of poorly water soluble drugs. To indicate uniformity of drug distribution in all the
increase the solubility and hence the bioavailability physical mixtures and solid dispersions of
it is important to increase the dissolution of the Cinnarizine.
poorly water soluble drugs. One of the possible In FTIR study were peaks of SD1:3 shows one
way to overcome this limitation is the use of solid additional peak at 3537.20 cm-1 than pure
dispersion technique. Cinnarizine is a H1 receptor Cinnarizine peaks, which is indicative of
antagonist is mostly prescribed in treatment of intermolecular hydrogen bonding between
motion sickness, vomiting and vertigo. It is BCS Cinnarizine and Soluplus. In DSC study
class II drug having low solubility and high thermogram of Cinnarizine shows sharp endotherm
permeability, and shows variable bioavailability at 121C indicating melting point of Cinnarizine.
and delay in onset of action. It is well established The thermogram of Soluplus shows change in heat
fact that, dissolution is the rate limiting step in the capacity at 81C indicating melting point of
absorption process. Conventional tablet of Soluplus. In SD 1:3 thermogram shows the
Cinnarizine is available in markets which are not reduction in melting point from 1210C to 1150C
suitable where fast onset of action is needed. and intensity of peak also reduced. This decrease in
In order to overcome above problems, the present melting point of Cinnarizine may attribute to
study was carried out to develop orodispersible crystalline to amorphous nature in solid dispersion.
tablets containing Cinnarizine solid dispersion. In order to investigate in-vitro release of pure drug,
Solid dispersions of Cinnarizine were prepared by physical mixtures and solid dispersions with
using novel polymer Soluplus in different ratios by Soluplus were subjected to dissolution study in
physical mixture and solvent evaporation method. USP type II dissolution apparatus. PD, PM1:1, 1:2
The drug and polymer ratio of 1:1, 1:2, 1:3 were and 1:3 shows 49.432 0.4227 %, 61.025 0.9124
used in order to enhance solubility and dissolution %, 66.669 0.8894 % and 75.916 0.4513 % drug
rate. After formulation completed Cinnarizine, release respectively in 30 min. Solid dispersion
physical mixture and solvent evaporation method SD1:1, SD1:2 and 1:3 shows 75.916 0.9570 %,
dispersions were proceeds for its evaluation study 98.893 0.2632% and 99.829 0.3998 % drug
Saturation solubility of Cinnarizine was found to be release in 30 min, 27 min and 24 min respectively.
0.6326 mg/ml and 0.0039 mg/ml in pH 1.2 buffer It indicate that SD1:3 shows higher drug release
solution and pH 6.8 phosphate buffer respectively. 99.82 0.3998 % within 24 min compared to PD,
Physical mixture and solid dispersion with PMs and SD1:1, 1:2. From the results of
Soluplus shows increase in solubility respectively. dissolution studies SD1:3 is selected as best
The ratio 1:3 of solid dispersion gives the formulation for tablet formulation.
maximum saturation solubility among all the Orodispersible tablets of SD1:3 were prepared by
physical mixture and solid dispersions i.e. 4.8460 using Kyron T-314 as a superdisintegrant in
mg/ml and 0.030684 mg/ml in pH 1.2 buffer different concentration 1 %, 2 %, 3 % and 4 % by
solution and pH 6.8 phosphate buffer respectively. direct compression method. These formulations are
Drug content was found to be in range 98.78 coded as F1, F2, F3 and F4. In order to establish

www.iajps.com Page 923


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

compatibility study, the FTIR spectra of Formulation of orodispersible tablet by using solid
formulation blend shows all characteristic peaks of dispersion of Cinnarizine is unique technique by
Cinnarizine and SD1:3 and it indicates that there is which solubility and bioavailability of drug can be
no any significance interaction between SD1:3 and enhanced with improving patient compliance and
Kyron T 314. convenience.
The blends of all the formulations were evaluated It can be concluded that combination of solid
for pre-compression parameters like angle of dispersion and superdisintegrant is a promising
repose, bulk density, tapped density, carrs index approach to prepare efficient orodispersible tablet
and housners ratio. The results that are obtained of BCS class II drug (low solubility, high
for formulation F1-F4 shows good compression permeability).
and flow property. The prepared tablets were Standardized orodispersible tablet formulation F4
subjected for post-compression parameters. The was found to be stable after three month
results for all formulations possessed good accelerated stability study.
mechanical strength with sufficient hardness in the Thus, the objectives of the research work were
range of 3.78 to 3.90 kg/cm2. The percent friability successfully achieved.
was found to be 0.4117 to 0.5616 which is less than
1m% indicating tablets were mechanically stable. REFERENCES:
All formulations show 199.7 to 200.25 mg/tablet 1.Das Sanjoy Kumar, Roy Sudipta, Yuvaraja
weight, which complies with pharmacopeias limit. Kalimuthu, Khanam Jasmina, Nanda Arunabha.
Drug contents were found to be within Solid dispersions: An approach to enhance the
pharmacopeias limit. The wetting time, dispersion bioavailability of poorly water soluble drugs,
time, disintegration time for all formulations was International Journal of Pharmacology and
found to be 14.0 to 31.33 sec., 19.33 to 34.33 sec. Pharmaceutical Technology, Vol.-I, Issue-1, p.37-
and 13.0 to 26.16 sec. It is decreasing wetting, 46.
dispersion and disintegration time with increasing 2.Sharma D, Soni M, Kumar S, Gupta GD.
concentration of Kyron T-314. Solubility enhancement eminent role in poorly
The in-vitro dissolution profiles were indicates soluble drugs. Research Journal of Pharma and
faster and maximum drug release from all Tech, 2009; 2 (2), p. 220-224.
formulations F1 to F4. F1 shows 99.1475 0.4240 3.Patel T, Patel L, Patel T, Makwana S, Patel T.
% in 24 min., F2 shows 99.498 0.4672 % in 21 Enhancement of dissolution of Fenofibrate by solid
min., F3 shows 99.4461 0.2273 % in 18 min and dispersion technique. International Journal
F4 shows 99.7582 0.6297 % in 15 min. Based on Research and Pharm Science 2010; 1(2), p. 127-
obtained results, the formulation F4 is selected as a 132.
best formulation and which is compared with 4.IlseWeuts, Dieter Kempena, Geert Verreck,
marketed formulation. Percent drug release of JefPeeters, Marcus Brewster, Norbert Blaton,. Salt
marketed formulation in 15 min was 66.9272 formation in solid dispersions consisting of
0.2321 % and F4 formulation was 99.7582 polyacrylic acid as a carrier and three basic model
0.6297 %. compounds resulting in very high glass transition
The prepared orodispersible tablet of Cinnarizine temperatures and constant dissolution properties
solid dispersion has shown better release and upon storage. European Journal of Pharmaceutical
stability as compared to marketed formulation. Science, 2005; 25, p. 387393.
The conclusions from present research work are as 5.Bramhmankar DM, Jaiswal SB,
follows: Biopharmaceutics and Pharmacokinetics- A
The use of Soluplus for obtaining solid dispersion Treatise, Vallabh Prakashan, Second edition, p. 24-
of Cinnarizine proved successful. 30, 314-336.
The significance increase in solubility and 6.Dhirendra K, Lewis S, Udupa N. Solid
dissolution was observed from solid dispersion dispersions: A review, Pak Journal of
containing Cinnarizine and Soluplus in 1:3 ratio Pharmaceutical Science, Vol 22, April 2009; p.
prepared by solvent evaporation method as 234-246.
compared to pure drug, physical mixtures and other 7.Kuchekar BS, Aruagam VA. Review: Fast
solvent evaporation method dispersions. dissolving tablets. Indian Journal of Pharmaceutical
Soluplus as a solid dispersion carrier imparts good Education, 2001; 35, p. 150-152.
surface adsorbent property and leaves drug in 8.Lindgreen S, Janzon L. Dysphagia: Prevalence of
amorphous state that increases the surface area, due swallowing complaints and clinical findings.
to enhances the dissolution rate. Medical Clinic of North America. 1993; 77, p. 3-5.
Formulation of orodispersible tablet of Cinnarizine 9.Bangale GS, Shinde GV, Stephen B. New
solid dispersion (1:3) by using Kyron T- 314 generation of orodispersible tablets: recent
showed rapid in-vitro disintegration and dispersion advances and future prospects, International
time.

www.iajps.com Page 924


IAJPS 2017, 4 (04), 910- 925 Dhananjay M.Patil et al ISSN 2349-7750

Journal of Advances in Pharmaceutical Sciences, 2, 22.Khan S, Kataria P, Nakhat P, Yeole P. Taste


2011; p. 17-28. masking of Ondensetron hydrochloride by polymer
10.Patel Bipin, Patel Jayvadan, Thakor Rashmin, carrier system and formulation of rapid
Rajput Ganesh, Patel Kalpesh. Improvement of disintegrating tablet. AAPS Pharmceutical Science
solubility of Cinnarizine by using solid dispersion and Techchnology. 2007; 8(2), p. 238-243
technique, International Research Journal of 23.Gandhi B. R., Mundada A. S., Gandhi K. R.,
Pharmacy, 2010; 1(1), p. 127-131. Evaluation of Kyron T-314 (polacrillin potassium)
11.Suresh Preeti K, Sharma Sudhanshu. as a novel superdisintegrant, International Journal
Formulation and in-vitro characterization of self- of Drug Delivery, Vol. 3, 2011; p. 109-114.
nanoemulsifying drug delivery system of 24.Natalie MC, Clure. Stability studies in overview
Cinnarizine , International Journal of of ICH Guidelines for Drug Products. Matrix
Comprehensive Pharmacy, 2011; Vol. 02, Issue 09, Pharmaceutical Inc., 1997.
p 1-6. (http://www.mcclurenet.com).
12.Bangale GS, Shinde GV, Stephen B. New
generation of orodispersible tablets: recent
advances and future prospects, International
Journal of Advances in Pharmaceutical Sciences, 2,
2011; p. 17-28.
13.Gandhi B. R., Mundada A. S., Gandhi K. R.,
Evaluation of Kyron T-314 (polacrillin potassium)
as a novel superdisintegrant, International Journal
of Drug Delivery, Vol. 3, 2011; p. 109-114.
14.Tiwari Ruchi, Tiwari Gaurav, Srivastava
Brijendra, Rai Awani, Radke R. Development and
optimization of multi-unit solid dispersion systems
of poorly water soluble drug, Research Journal of
Pharm. and Tech. Oct-Dec 2008; 1(4), p. 444-449.
15.Shinde Sharad N, Satej S. Magdum, Kamla K.
Chandak, Mahesh R. Mishra, Smita S. Singhal.
Modification of solubility characteristics of
cinnarizine using -cyclodextrin, International
Imperial Journal Pharmaceutics & Cosmetology
2(1): May 2012; p. 30-36.
16.Pokharkar Varsha, Mendiratta Charu, Kadam
Vivek, Lansoprazole solid dispersion using a novel
amphiphilic polymer Soluplus, Journal of Chemical
and Pharmaceutical Research, 2011; 3(6), p. 536-
543.
17.Bahar Kalava, Muzeyyen Demirel, Yasemin
Yazan, Physicochemical characterization and
dissolution properties of Cinnarizine solid
dispersions, Turkish Journal of Pharmaceutical
Science Vol 2, 2005, p. 51-61.
18.The United State Pharmacopoeia 28 / The
National Formulary 23, Asian edition, The Official
Compendia of Standards, United State
Pharmacopoieal Conviction Inc. Rockville, 2004;
p. 2724-2725, 2412-14, 2379-2380, 2000,1675.
19.Remington. The science and practice of
pharmacy. 20th Ed: B.I. Publications Pvt. Ltd:
2000; 1, p. 858-862.
20.Lachman L. Libberman HA, Kanig JL. Theory
and Practice of Industrial Pharmacy. 3rd edition
Varghese publishingn house, 1990; p. 296-302
21.Yunxia B, Sunada H, Yonezawa Y, and Danjo
K. Evaluation of rapidly disintegrating tablets
prepared by direct compression method. Drug
Devlivery of Indian Pharma 1999; 25(5), p. 571-
581.

www.iajps.com Page 925