Indo American Journal of Pharmaceutical Research, 2013 ISSN NO: 2231-6876

INDO AMERICAN
Journal home page: JOURNAL OF
http://www.iajpr.com/index.php/en/ PHARMACEUTICAL
RESEARCH

FORMULATION AND DESIGN OF TASTE MASKED QUETIAPINE FUMARATE

ORALLY FAST DISINTEGRATING TABLETS BY SUBLIMATION METHOD
Mettu Srikanth Reddy1, N. G. Raghavendra Rao*1, Krishna. D2
1
Department of Pharmaceutics, Jyothishmathi Institute of Pharmaceutical Science, Thimmapur, Karimnagar - 505481, AP. India.
2
Department of Pharmaceutics, St. Peter’s Institute of Pharmaceutical Sciences, Warangal -506001, AP, India.

ARTICLE INFO ABSTRACT

Article history Quetiapine Fumarate bioavailability is 9%. Used in the treatment of schizophrenia.
Received 20 Dec 2012 It is preferable to administer in the form of fast disintegrating tablets used for
Available online xxxxx depressive episodes, acute manic episodes associated with bipolar I disorder at a
short time. In present research work an attempt has been made to prepare taste
masked fast dissolving tablets of Quetiapine Fumarate were prepared by using
sublimation method. Crosspovidone is used as a superdisintegrant. Camphor, Urea
Keywords and Menthol are used as a sublimating agent. The prepared tablets were evaluated
Fast dissolving for various parameters like weight variation, hardness, friability, disintegration
tablet, time, drug content, water absorption ratio, wetting time, in-vitro drug release, FTIR
studies and short term stability studies. IR spectral analysis study showed that there
Quetiapine was no drug interaction with formulation additives of the tablet. The blend was
Fumarate, examined for the pre-compressional parameters. The prepared tablets formulations
Crosspovidone, were evaluated for post-compressional parameters. The values of pre-compression
Camphor, parameters evaluated were within prescribed limits and indicated good free flowing
Menthol, property. All the post-compressional parameter are evaluated were prescribed
limits and results were within IP acceptable limits. The disintegration time of 15 to
Disintegration time. 68 sec, water absorption ratio of 66.75 to 83.52%, wetting time of 32 to 61.22 sec.
In-vitro dissolution studies of all the formulations were carried various dissolution
parameter values viz., percent drug dissolved in 4 min, 8 min, 12 min, 16 min, 20
min, 24 min, and 28min (D4, D8, D12, D16, D20, D24, and D28), t50% and t90%. This data
reveals that overall, the formulation SQF1, SQF2, SQF3 and SQF9 shows nearly
faster drug release. The formulations SQF1, SQF2, SQF3 and SQF9 50 % of drug
released in 0.92 min, 0.80min, 0.65 min, and 0.86 min respectively, and 90 % of
drug released in 5.90 min, 4.88 min, 2.89 min and 6.98 min, respectively when
compared to other tablet formulation. Among all the formulation SQF3 were found
to be promising and showed a disintegration time of 15 sec, 50 % of drug released
in 0.65 min, and 90 % of drug released in 2.89 min. The results obtained showed
that the quantity of Crosspovidone and camphor significantly affect response
variables. The stability study conducted as per the ICH guidelines and the
formulations were found to be stable. The results concluded that fast dissolving
tablets Quetiapine Fumarate showing enhanced dissolution, will lead to improved
bioavailability, improved effectiveness and hence better patient compliance.
1446

Corresponding author: Dr. N. G. Raghavendra Rao, Principal and HOD, Jyothishmathi Institute of Pharmaceutical Science, Ramakrishna Colony,

Thimmapur, KARIMNAGAR-505481, Andhra Pradesh, Mob No: +919966794479, +919448570193

Page

Email: ngraghu@rediffmail.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

INTRODUCTION:
Quetiapine Fumarate bioavailability is 9%. Half-life of drug is Approximately 6 hrs. Quetiapine
Fumarate is a psychotropic agent belonging to a chemical class, the dibenzothiazepine derivatives. Used in the
treatment of schizophrenia. It is preferable to administer in the form of fast disintegrating tablets used for
depressive episodes, acute manic episodes associated with bipolar I disorder at a short time 1-3.
Most pharmaceutical forms for oral administration are formulated for direct ingestion, for chewing, for
prior dispersion and /or dissolution in water; some of them are absorbed in mouth (sublingual or buccal tablets).
Elderly individuals have difficulty in swallowing when prescribed in conventional tablet and capsule form 4-6.
The problem of swallowing is also evident in pediatrics, psychiatric as well as travelling patients who may not
have ready access to water 7.The rapidly disintegrating tablet in mouth or oro dispersible tablets overcome all
the above problems and thus offer an alternate form of oral medication, which provide patient s with a more
convenient means of taking their medication 8. Addition of super disintegrating agent in the formulation is one
of the approaches to formulate oro dispersible tablets 9-15.
Orally Disintegrating tablets (ODTs) rapidly disintegrate in the mouth without chewing upon oral
administration and without the need for water, unlike other drug delivery systems and conventional oral solid
immediate-release dosage form. ODT dosage forms, also commonly known as fast melt, quick melts, fast
disintegrating and orodispersible systems have the unique property of disintegrating the tablet in the mouth in
sec.
The desired criteria for the FDT they should Have a pleasing mouth feel, Leave minimal or no residue in
the mouth after oral administration and not require water to swallow, but it should dissolve or disintegrate in the
mouth in a matter of sec 16-17. Most commonly used methods to prepare these tablets are; freeze-
drying/Lyophilization18 tablet molding19 and direct-compression methods20. Lyophilized tablets show a very
porous structure, which causes quick penetration of saliva into the pores when placed in oral cavity18,21.
Moulded tablets dissolve completely and rapidly. However, lack of strength and taste masking are of great
concern22. Main advantages of direct compression are low manufacturing cost and high mechanical integrity of
the tablets23. Therefore, direct-compression appears to be a better option for manufacturing of tablets.
In present research work an attempt has been made to prepare fast dissolving tablets of Quetiapine
Fumarate by using sublimation method. The fast disintegrating tablets are prepared by sublimation method, in
general based on the action established by superdisintegrant such as Crosspovidone and sublimating agents such
as camphor, urea and menthol. Effects of sublimated tablets (Drug, polymer and sublimating agent) on wetting
time, disintegrating time, drug content, in-vitro release, and stability studies parameters have been studied.

MATERIALS AND METHODOLOGY:

Materials:
Quetiapine Fumarate was procured from Gift sample from Aan Pharma Ltd. Gujarat. Crosspovidone was
procured as a gift sample from Signet (Mumbai), Mannitol, MCC, aspartame, talc and magnesium stearate
purchased from S.D. Fine chem., Mumbai. All other materials were of analytical reagent grade.
1447

Preparation of Drug Polymer Complex:

Quetiapine Fumarate and Eudragit E100 complex was prepared by solvent evaporation method. Saturated stock
solutions of Quetiapine Fumarate and Eudragit E100 were prepared in absolute Ethanol. Aliquots of drug and
Page

polymer solutions were taken to obtain various ratios (1:0.5, 1:1, 1:2, 1:3) and mixed continuously at 150 rpm
on a magnetic stirrer. Stirring was allowed to continue until the solvent is completely evaporated. After this

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

mixture was kept at 35oC for 2 hours and dried under vacuum for 24 hrs to obtain a hard matrix. Then the hard
matrix is subsequently pulverized and screened through 60 mesh to obtain the uniform sized fine powder of
drug polymer complex (DPC) and it was finally stored in a tightly closed container for further studies.

Taste evaluation:
Taste evaluation was performed on six healthy human volunteers for pure drug, and for four different ratios of
drug: polymer. Bitterness was recorded immediately and at several intervals for 5 min according to the
bitterness intensity scale from 0 to 5 where 0, 0.5, 1, 2, and 3 indicate no, threshold, slight, moderate, and strong
bitterness.

Preparation of fast dissolving tablets by direct compression technique 24:

The basic principle involved in preparing fast dissolving tablets by sublimation technique shown in Fig 1 using
inert sublimating agents and crosspovidone were added to other tablet excipients and the blend was compressed
into tablet. Removal of volatile material by sublimation generated a porous structure. Accurately weighed
ingredients were sifted through sieve no.44 and thoroughly mixed for 10 min and magnesium stearate and other
ingredients were added to the blend and thoroughly mixed. The tablets were compressed using Rimek tablet
punching machine. The composition of the tablets was given in Table 1. The compressed tablets were than
subjected to sublimation at 50 C for 60 min. The tablets were evaluated for disintegration time and mean tablet
weight. The tablets dissolve within 10-20 sec. and exhibit sufficient mechanical strength for practical use.

Drug + Camphor + Other Excipients

Compression

Camphor

Lactose
Compressed Tablet

Sublimation

o o o o o o Pores developed on
o o o o o Sublimation of Camphor
o o o o o o

Fig 1: Schematics figure of Sublimation method for design of Mouth dissolving tablets
1448
Page

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Table 1: Formulation of Quetiapine Fumarate fast dissolving tablets prepared by

sublimation method (1-tablets)
Ingredient Formulation code
(mg) SQF1 SQF2 SQF3 SQF4 SQF5 SQF6 SQF7 SQF8 SQF9
QF 50 50 50 50 50 50 50 50 50
CP 24 24 24 24 24 24 24 24 24
Camphor 10 15 20 -- -- -- -- -- --
Urea -- -- -- 10 15 20 -- -- --
Menthol -- -- -- -- -- -- 10 15 20
Aspartame 6 6 6 6 6 6 6 6 6
D-M 45 45 45 45 45 45 45 45 45
MCC 47 42 37 47 42 37 47 42 37
PVP 15 15 15 15 15 15 15 15 15
Talc 1 1 1 1 1 1 1 1 1
Mg St 2 2 2 2 2 2 2 2 2
Total 200 200 200 200 200 200 200 200 200

Note: QF=Quetiapine Fumarate, CP=Crosspovidone, D-M=D-Mannitol, MCC=Microcrystalline cellulose

(Avicel PH-102), Mg St= Magnesium stearate.
After compression the tablets were collected and vacuum dried in a vacuum oven at 80° C until a
constant weight was obtained to ensure the complete removal of sublimable component to make the tablet
porous (Table 2).

Evaluation of Quetiapine Fumarate tablets:

Micromeritic properties of powder blend of tablets before compression: the prepared tablet blends are evaluated
for different tests like angle of repose, apparent bulk density, tapped density, percent compressibility and
Hausner ratio,

Evaluation of Tasted masked Quetiapine Fumarate Fast Disintegrating Tablets25-28:

Weight variation: Average weight of 20 tablets is calculated using an electronic balance. Individual weight of
each tablet is calculated and compared with the average weight. The Mean ± SD and RSD were noted. The
tablets meet USP specifications if no more than 2 tablets outside the percentage limit and if no tablet differs by
1449

more than 2 times the percentage limit.

Tablet Thickness: Randomly 10 tablets should be taken and thickness was measured for each tablet by placing
it between two anvils and rotating the sliding knob until the tablet was tightly fitted and the reading was noted.
Page

The tablet thickness should be controlled within a ±5% variation of a standard value.

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Hardness and Friability: Tablet hardness has been defined as “the force required to break a tablet in a
diametric compression test”. To perform this test, the tablet is placed between two anvils, force is applied to the
anvils, and the crushing strength that just causes the tablet to break is recorded. Hardness is thus sometimes
called as “tablet crushing strength”. Several devices that commonly serve the purpose of determining the tablet
hardness are the Monsanto tester, the Strong-cobb tester, the Pfizer tester, the Erweka tester and the Schleuniger
tester.

Table 2: Tablet weight before vacuum drying (BVD) and after vacuum drying
(AVD)

Formulation Tablet Weight

BVD AVD

SQF1 201 (0.54) 176 (0.63)

SQF2 200 (0.62) 180 (0.58)

SQF3 202 (0.34) 178 (0.68)

SQF4 199 (0.44) 161 (0.82)

SQF5 202 (0.67) 165 (0.92)

SQF6 200 (0.98) 158 (0.36)

SQF7 201 (0.28) 149 (0.72)

SQF8 200 (0.66) 152 (0.76)

SQF9 201 (0.92) 148 (0.64)

Hardness of tablet was determined by using a Monsanto tablet hardness tester (Cadmach Machinery Co,
Ahmadabad, India). Friability of ten tablets from each formulation was determined using the Roche friabilator
(Campbell Electronics, Mumbai, India). This device subjects a no of tablets to the combined effect of abrasions
and shock by utilizing a plastic chamber that revolves at 25 rpm dropping the tablets at distance of 6 inches with
each revolution. Pre-weighed sample of tablets was placed in the friabilator, which was then operated for 100
revolutions. Tablets were dusted and re-weighed.

Content uniformity: Six tablets from each formulation were taken randomly and powdered. A quantity of
powder equivalent to weight of one tablet was transferred in to a 100mL volumetric flask, containing 0.1 N
HCL and mixed thoroughly for few minutes and the volume was made up to 100mL with 0.1 N HCL. The
1450

solution was filtered through whatman filter paper and suitably diluted with the same medium and the drug
content was estimated from the standard plot by measuring the absorbance at 290 nm using UV-Visible
spectrophotometer.
Page

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

In vitro disintegration time: In vitro disintegration time of FDTs was determined by following the procedure
described in earlier reports (Gohel et al., 2004). Briefly 10 mL of 0.1N HCL at room temperature was taken in a
petri dish of 10cm in diameter. The tablet was then carefully placed in the centre of petri dish and the time
required for the tablet to completely disintegrate into fine particles was noted. Measurements were carried out in
triplicates.

Wetting time and water absorption ratio: The wetting time of the tablets was measured using a simple
procedure. Five circular tissue papers of 10-cm diameter were placed in a Petri dish with a 10-cm diameter. Ten
milliliters of water containing a water-soluble dye was added to the petri dish. A tablet was carefully placed on
the surface of tissue paper in the petri dish at room temperature. The time required for water to reach the upper
surface of the tablets and completely wet them was noted as the wetting time. To check for reproducibility, the
measurements were carried out (n=6) and the mean value was calculated.
The weight of the tablet before keeping in the petri dish was noted (Wb). The wetted tablet from the petri
dish was taken and reweighed (Wa). The Water absorption ratio, R, was determined according to the following
equation:
R = 100 (Wa - Wb) / Wb
Where Wb and Wa are the weight before and after water absorption respectively.
Measurement of wetting time of a tablet was shown in Fig 2.

10.75 cm
12 cm

Petridish (i.d=6.5 cm)

Tablet

Tissue Paper

Tissue Paper
Fig 2: Simple method for the measurement of wetting time of a tablet.
Simple Method for the Measurement of Wetting Time of a Tablet
In vitro Dissolution Studies 29: The in vitro dissolution study of taste masked Quetiapine Fumarate
FDTs were performed using USP type II (paddle) apparatus. The dissolution medium consists of
900mL of 0.1N HCL thermostated at 37±0.5°C and stirred continuously at 50 rpm through out the
experiment. An aliquot of 5mL was collected at predetermined time intervals (5, 10, 20, 30, 45, 60
min) and replaced with fresh dissolution medium. The samples were filtered, by passing through
1451

0.45 µm membrane filter and analyzed spectrophotometrically at 290 nm. Dissolution rate was
studied for all designed formulations.
Page

Fourier Transform Infrared Spectroscopy (FTIR): The chemical interaction between the drug and polymer
was evaluated by subjecting drug, polymer, DPC to FTIR studies. FTIR spectra were obtained on Shimadzu

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

FTIR (Shimadzu Corp., India). Samples were prepared in KBr disks, the scanning range was 4000 and 400 cm -
1
.
The stability study of the tablets was carried out according to International conference on Harmonization
guidelines for zone III and IV. The formulations were stored at (25°C/60% RH) and (40°C/75% RH for three
months by storing the samples in stability chamber (Thermo Lab, Mumbai). The promising formulations were
subjected to short term stability study. The formulations SQF3, SQF6 and SQF9 were selected.
RESULT AND DISCUSSION:
Taste evaluation: Taste evaluation was performed on six healthy human volunteers and the results were
reported in the Table 3. The pure drug was felt bitter immediately after it was kept on the tongue and the sense
was even carried up to 5 min. However the bitterness of the drug was reduced or even masked after
complexation with eudragit EPO in different ratios ( 1:0.5, 1:1, 1:2, 1:3). In case of 1: 0.5 ratio it was felt
slightly bitter after 1 min and it is apparent from the results that the increasing concentrations of the polymer
have completely have completely masked the bitter taste of the drug. Since the drug is not in the native form
and entrapped with in the polymeric matrix, and there by reduction in the solubility of the drug in the saliva
could have led to the masking of the bitter taste. Even though the Quetiapine Fumarate taste was masked with
drug polymer complex (1:0.5, 1:1, 1:2, 1:3) ratios, we have selected 1:1 for further studies, since higher
amounts of polymer may retard the dissolution performance of the final fast disintegrating tablets of Quetiapine
Fumarate. Erythritol (1%w/w) was included in all the formulations to improve the palatability.

Table 3: comparative taste evaluation.

Form of

Quetiapine 10 sec 30 sec 1 min 2 min 5 min

Fumarate

Pure drug 3 3 3 3 2

DPC (1:0.5) 0.5 1 1 1 0

DPC (1:1) 0 0 0.5 0.5 0

DPC (1:2) 0 0 0.5 0 0

DPC (1:3) 0 0 0.5 0 0

The values of pre-compression parameters evaluated were within prescribed limits and indicated good free
flowing property (Table 4). All the post compressional parameter are evaluated were prescribed limits and
results were within IP acceptable limits. Results were shown in (Table 5). In all the formulations, hardness test
indicated good mechanical strength ranges from 2.6 to 3.3kg/cm².The friability range is 0.63 to 0.74 % to be
well within the approved range (<1%)indicated that tablet had good mechanical resistance. The weight variation
1452

was found in all designed formulations in the range 195 to 200 mg. All the tablets passed weight variation test
as the average percentage weight variation was within 7.5% i.e.in the pharmacopoeia limits. The thickness was
almost uniform in all the formulations and values ranged from 3.48 mm to 3.74 mm. The standard deviation
Page

values indicated that all the formulations were within the range. Rapid disintegration within several minutes was
observed in all the formulations. The in-vitro disintegration data is tabulated in the (Table 6) and Fig 3. The in-

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

vitro disintegration time of fast dissolving tablets were found to be 15 to 68 sec. which is in the range of
fulfilling the official requirements. By the addition of superdisintegrants the disintegration time increased
significantly (P<0.05) tablets prepared.Based on the in-vitro disintegration time, formulation SQF3 were found
to be promising and showed a disintegration time of 15 sec. These results suggest that the disintegration times
can be decreased by using wicking type disintegrants (Crosspovidone).Wetting time is closely related to the
inner structure of the tablet. The wetting time of Quetiapine Fumarate tablets were found to be in the range of
22.62 to 88.62 sec. The water absorption ratio in the range 71.32 to 84.41%. The percentage drugs content of
the tablets were found to be between 97.46 to 99.66% of Quetiapine Fumarate. The results were within the
range and that indicated uniformity of mixing. The wetting time, water absorption ratios and drug content
results were tabulated in the Table 6.
Table 4: Pre-compression parameters Quetiapine Fumarate fast dissolving tablets.
Bulk Tapped Percent
Formulation Angle of Hausner’s
Density Density Compressibility
code Repose ( ° ) Ratio
(gm/cm3) (gm/ cm3) Index (I)
SQF1 36.4 0.48 0.62 22.58 1.29
SQF2 37.2 0.51 0.61 16.39 1.19
SQF3 37.5 0.49 0.6 18.33 1.22
SQF4 33.2 0.5 0.58 13.79 1.16
SQF5 30.5 0.48 0.58 17.24 1.20
SQF6 26.8 0.51 0.59 13.55 1.15
SQF7 27.4 0.52 0.59 11.86 1.13
SQF8 30.2 0.50 0.60 16.66 1.20
SQF9 26.3 0.48 0.62 22.58 1.29
* Average of three determinations
Table 5: Post-compression parameters Quetiapine Fumarate fast dissolving tablets

Hardness * Friability Thickness* Weight variation*

FC (Kg/cm²) (%) (mm) (mg)
SD SD SD
SQF1 3.2 0.16 0.63 0.02 3.64 0.12 200.00 1.2
SQF2 3.1 0.15 0.65 0.06 3.48 0.14 198.32 1.6
SQF3 2.6 0.12 0.68 0.12 3.52 0.12 199.98 1.2
SQF4 3.2 0.14 0.69 0.06 3.62 0.14 199.42 1.0
SQF5 2.7 0.12 0.68 0.14 3.72 0.5 198.75 0.6
SQF6 2.8 0.16 0.70 0.12 3.66 0.12 199.59 1.2
SQF7 2.9 0.12 0.72 0.18 3.74 0.14 199.99 1.6
1453

SQF8 3.1 0.22 0.71 0.12 3.48 0.06 199.54 1.2

SQF9 3.3 0.14 0.74 0.14 3.62 0.12 197.84 1.6
* Average of three determinations
Page

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Table 6: Post-compression parameters Quetiapine Fumarate fast dissolving tablets

Disintegration Wetting time* Water absorption Drug Content*
FC time* (sec) SD ratio* SD (%) SD
(sec) SD
SQF1 27.02 1.2 28.42 1.2 84.41 1.4 99.66 1.1

SQF2 22.60 0.8 24.41 1.2 82.98 1.2 98.42 1.2

SQF3 15.12 0.9 22.62 1.2 80.43 1.4 99.24 1.4

SQF4 68.01 1.4 88.62 0.8 78.32 1.0 97.88 0.4
SQF5 49.36 1.2 74.32 0.4 75.32 1.2 99.46 0.2
SQF6 38.46 1.6 33.62 1.2 71.87 1.4 98.50 1.2
SQF7 39.84 1.2 38.14 1.2 75.50 1.6 97.46 1.1
SQF8 28.46 0.6 30.34 1.4 72.42 1.4 97.88 0.2
SQF9 21.62 0.8 25.31 0.6 71.32 1.2 98.74 1.2

* Average of three determinations

Fig 3: Disintegration time v/s. Formulation (SQF1 – SQF9).

1454

In-vitro dissolution studies of all the formulations were carried out in 0.1N HCL, the release results were
Page

shown in Figs 4-6. All the formulations were carried out various dissolution parameter values viz., percent
drug dissolved in 4 min, 8 min, 12 min, 16 min, 20 min, 24 min, and 28min (D4, D8, D12, D16, D20, D24, and D28),

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

t50% and t90% are shown in Table 7 . This data reveals that overall, the formulation SQF1, SQF2, SQF3 and
SQF9 shows nearly faster drug release.
The formulations SQF1, SQF2, SQF3 and SQF9 50 % of drug released in 0.92 min, 0.80min, 0.65 min,
and 0.86 min respectively, and 90 % of drug released in 5.90 min, 4.88 min, 2.89 min and 6.98 min,
respectively when compared to other tablet formulation. Among all the formulation SQF3 were found to be
promising and showed a disintegration time of 15 sec, 50 % of drug released in 0.65 min, and 90 % of drug
released in 2.89 min.
The Table 8 shows the parameters of the tablets after stability study. The promising formulations were
subjected to short term stability study by storing the formulations at 25oC/65% and 40oC/75% RH up to three
month. The formulations SQF3, SQF6 and SQF9 were selected. After three month the tablets were again
analyzed for the hardness, friability, drug content uniformity and disintegration time. Decrease in the
disintegration time was observed in tablets prepared by camphor sublimation method. Since during the
preparation of tablets by camphor sublimation method, only 6 hrs at 50°C was used, where as 90 days and 45°C
were used during stability studies.

Fig 4: Release profile of formulation containing camphor (SQF1-SQF3)

1455
Page

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Fig 5: Release profile of formulation containing urea (SQF4-SQF6)

1456
Page

Fig 6: Release profile of formulation containing menthol (SQF7-SQF9)

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Table 7: In-vitro release profile of Quetiapine Fumarate fast dissolving Tablets

FC Parameters
D4 D8 D12 D16 D20 D24 D28 D t 50% D t 90%
SQF1 74.87 96.73 -- -- -- -- -- 0.92 min 5.90 min
SQF2 85.75 99.93 -- -- -- -- -- 0.80 min 4.88 min
SQF3 97.40 -- -- -- -- -- -- 0.65 min 2.89 min

SQF4 47.95 57.57 67.31 74.77 83.40 91.58 98.02 5.69 min 23.58 min

SQF5 52.33 61.64 71.06 79.84 92.88 99.88 -- 3.82 min 19.38 min

SQF6 61.82 73.42 84.05 93.15 99.80 -- -- 1.81 min 15.4 min

SQF7 64.17 80.04 94.59 -- -- -- -- 1.96 min 10.81 min

SQF8 67.15 87.64 99.23 -- -- -- -- 1.00 min 8.95 min

SQF9 74.18 94.30 -- -- -- 0.86 min 6.98 min

In the present study the IR spectra for pure drug Quetiapine Fumarate and its formulations with various
polymers and other excipients is taken to establish the physical characterization of drug and its formulations
(Fig 7). FTIR analysis was used to study the possible chemical interaction between the drug and polymer. The
pure drug which is an dibenzothiazepine derivatives showed a characteristic peak at 3317.5 cm-1 this is due to
N-H stretching and peaks at 1598.99 cm-1and 1571.99 cm-1 indicative of the N-H deformation. The peak at
1336.67 cm-1 is due to the C-O stretching and peaks at 1458.18 cm-1 and 1413.82 cm-1 are indicative of C=C
stretching of aromatic nucleus. Eudragit E100 which is an methacrylic acid ester showed important peaks at
1732.08 cm-1 indicative of C=O stretch of the ester group. The peaks at 2954.95 cm-1 indicative of C-H stretch
in the alkane and 2769.78 cm-1 and 2821.86 cm-1 can be assigned to the dimethyl amino group.
The FTIR spectra of Drug Polymer Complex (DPC) displayed all the characteristic peaks of both drug
and polymer. The N-H and C-O stretch band of drug and C=O stretch and C-H stretch in dimethyl amino group
and C-H stretch in alkane of the polymer bands were detected in the same position. Consequently the FTIR of
DPC and physical mixture seemed to be summation of drug and eudragit E100. The physical mixture showed
additional characteristic peak at 3385.07 cm-1 indicative of free O-H stretch. Overall there was no alteration in
the characteristic peaks of drug and polymer in the DPC suggesting that there was no interaction between the
drug and polymer. 1457
Page

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Table 8: Result for promising Quetiapine Fumarate fast dissolving tablets

at (25°C/60% RH) and (40°C/75% RH) for 3 months.

Hardness percentage Dispersion

Sl. No. FC Month
Kg/cm² Friability time (sec)

(25°C/60% RH)
1st 3.2 0.63 27.02
1 SQF1 2nd 3.2 0.64 28.14
3rd 3.3 0.65 29.06
1st 3.1 0.65 22.60

2 SQF2 2nd 3.1 0.66 23.34

3rd 3.3 0.67 24.46

1st 2.6 0.68 15.12

3 SQF3 2nd 2.8 0.69 16.22
3rd 2.8 0.70 17.46
1st 3.3 0.74 21.62
4 SQF9 2nd 3.4 0.73 22.42
3rd 3.4 0.75 23.64

(40°C/75% RH)

1st 3.2 0.63 27.02

5 SQF1 2nd 3.3 0.65 28.42
3rd 3.4 0.66 29.32
st
1 3.1 0.65 22.60
6 SQF2 2nd 3.2 0.67 23.44
3rd 3.3 0.67 24.62
1st 2.6 0.68 15.12
7 SQF3 2nd 2.7 0.69 16.64
3rd 2.9 0.71 17.82
1st
1458

3.3 0.74 21.62

8 SQF9 2nd 3.4 0.72 22.21
Page

3rd 3.5 0.75 23.82

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

Fig 7: FTIR spectra of pure drug Quetiapine Fumarate and formulations SQF1, SQF2, SQF3 and SQF9.

CONCLUSION:
The above results concluded that, although differences existed between the superdisintegrants, the fast
dissolving Quetiapine Fumarate tablets could be prepared by using any of the superdisintegrants used. Overall
results indicates that formulation SQF3 which contain 15% Crosspovidone and camphor was better one and
satisfies all the criteria as fast dissolving tablet. Quetiapine Fumarate showing enhanced dissolution, may lead
to improved bioavailability, improved effectiveness and hence better patient compliance.

1459
Page

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

REFERENCES:
1. Seroquel XR Sustained-Release Tablets information http://www.drugs.com/mtm/ seroquel.htm.
2. Bauer M, Pretorius H, Constant E, Earley W, Szamosi J, Brecher M. Extended release Quetiapine as
adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-
controlled, double-blind study. J Clin Psychiatry. 2009;70:540-549.
3. El-Khalili N, Joyce M, Atkinson S, Buynak R, Datto C, Lindgren P, Eriksson H, Brecher M. Adjunctive
extended release Quetiapine Fumarate (Quetiapine XR) in patients with major depressive disorder and
inadequate antidepressant response. Poster presented at: the 161st Annual Meeting of the American
Psychiatric Association; May 3-8, 2008; Washington, DC.
4. Rajitha K, Shravan YK, Adukondalu D, Ramesh G, and Rao YM. Formulation and evaluation of orally
disintegrating tablets of buspirone. Int. J. Pharmaceutical Sciences and Nanotechnology. 2009; 1(4): 327-
334.
5. Chang RK, Guo X, Burnside BA, Couch RA. Fast dissolving tablets. Pharm. Tech. 2000; 24(6): 52-58.
6. Yeola BS, Pisal SS, Paradhkar AR, and Mahadik KR. New drug delivery systems. Indian Drugs.2000;
37(7):312-18.
7. Sastry SV, Nyshadham JR, and Fix JA. Recent technological advances in oral drug delivery - A Review.
Pharm. Sci. Tech. Today.2000;3(4):138-45.
8. Ito A, and Sugihara M. Development of oral dosage forms for elderly patients: Use of ager as base of
rapidly disintegrating oral tablets. Chem. Pharm. Bull. 1996; 44(11): 2132-36.
9. Watanabe Y, Koizumi K, Zama Y, Kiriyama M, Matsumoto Y, and Matsumoto M. New compressed
tablet rapidly disintegrating in saliva in saliva in the mouth using crystalline cellulose and a disintegrant.
Biol. Pharm. Bull. 1995; 18 (9):1308-10.
10. Bi Y, Sunada H, Yonnezawa Y, Danjo K, and Lida K. Preparation and evaluation of a compressed tablet
rapidly disintegrating in orall cavity. Chem .Pharm. Bull. 1996; 44(11): 2121-27.
11. Watanabe Y, Ishikawa T, Utoguchi N, and Matsumoto M. Preparation and evaluation of rapidly
disintegrating in saliva containing bitter taste- masked granules by the compression method. Chem.
Pharm. Bull. 1999; 47 (10):1451-54.
12. Gills PMV and Deconde VFV. Fast-dissolving galanthamine hydrobromide tablet. US Patent. 2000 ;(
6)099.863.
13. Makooi-Morehead WT, Buehler JD and Landmann BR. Formulation of fast dissolving efavirenz capsules
or tablets using superdisintegrants, US patent. 2001 ;(6): 238, 695.
14. Grassano A, Marchiorri M, Ditoro M, Castegin F. Fast dissolving compositions having analgesic activity.
US patent. 2001;(6): 197, 336.
15. Ishikawa T, Kuizumi N, Mukai B, Utoguchi N, Fujii M. Matsumoto M, Endo H, Shirrotake S, and
Watanabe Y. Preparation of rapidly disintegrating tablets using new types of microcrystalline cellulose
(Ph. M Series) and L-HPC by direct compression method. Chem. Pharm. Bull. 2001; 49 (27): 134-39.
16. Nangude TD, Chatap VK, Bhise KS, Sharma D.K. Mouth dissolving tablets: Geriatrics and pediatrics
friendly drug delivery system. Ind Drugs. 2007; 44(6): 471-3.
1460

17. Indurwade NH, Rajyaguru TH, Nakhat PD. Novel approach- Fast dissolving tablets. Ind Drugs. 2002;
39(8): 405-8.
18. Virley P, Yarwood R Zydis; A novel fast dissolving dosage form. Manu Chem. 1990; 61:22-9.
Page

19. Dobetti L; Fast-melting tablets: Developments and technologies. Pharm Technol Eur. 2000; 12:32-42.

www.iajpr.com
Vol 2, Isuue 12, 2013. Mettu Srikanth Reddy et al. ISSN NO: 2231-6876

20. Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, Iida K; Preparation and evaluation of a compressed
tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull. 1996; 4:2121-7.
21. Patrick K, Sang K W; Method of making freeze-dried dosage form. US Patent 5 631 023; 1997.
22. Chang R K, Guo X, Burnside B, Couch R; Fast dissolving tablets. Pharm Technol. 2000; 24:52-8.
23. Takao M, Yoshinori M, Muneo F; Intra-buccally dissolving compressed mouldings and production
process thereof. US patent 5 576 014; 1996.
24. Lachman L, Libermann HA, Kanig JL. The theory and practice of industrial pharmacy. Varghese
Publishing House, 3rd edition; 1991; 297-301.
25. Vijaya KS, Mishra DN. Rapidly disintegrating oral tablets of meloxicam. Ind Drugs. 2006; 43(2): 117-21.
26. Raju SA, Rampure MV, Shrisand SB, Swamy PV, Nagendra DK, Basawaraj B, Raghunandan D.
Formulation and evaluation of orodispersible tablets of alfuzosin. Int. J Pharm. Tech. Res. 2010; 2 (1): 84-
88.
27. Stephen BR, Rajveer CH, Sudarshini SA, Kishore Reddy. Preparation and evaluation of mucoadhesive
microcapsules of nimodipine. Int. J Res. Pharm. Sci. 2010; 1(2): 219-224.
28. Desai SA, Kharade SV, Petkar KC and Kuchekar BS. Orodissolving tablets of promethazine
hydrochloride. Ind J Pharm Edu Res. 2006; 40(3): 172-4.
29. Stephen BR, Rajveer CH, Prashant KC, Ganesh SB, Gajanan VS. Studies of dissolution behavior of
sustained release solid dispersions of nimodipine. Int. J Pharm. Review and Res. 2010; 3(1): 77-82.

75754552544547454

Submit your next manuscript to IAJPR and take

advantage of:
• Access Online first
• Double blind peer review policy
• No space constraints
• Rapid publication
• International recognition
Submit your manuscript at:
editorinchief@iajpr.com
1461
Page

www.iajpr.com