SlideShare a Scribd company logo
1 of 40
“DESIGN AND EVALUATION OF
BILAYER TABLETS OF CAPECITABINE
AND ONDANSETRON”
Register number: 261311006
DEPARTMENT OF PHARMACEUTICS Under the guidance of
CHERRAAN’S COLLEGE OF PHARMACY Dr. N. THIRUMOORTHY,
COIMBATORE-641039 M. PHARM, PH.D.,
It comprises of two layers, one of which is sustained release of
Capacetabine and another one is immediate release of
Ondansetron.
Hence, it uses Dual Release Drug Absorption System(DUREDAS)
technology.
 To provide once a day dosage form for the treatment of nausea
and vomiting .
 As Capacetabine having shorter half life, bilayer tablet provide
extended release of Capacetabine .
 Hence reduce dose frequency. Also, Ondansetron formulated as
an immediate release part provides initial relief as is the case with
loading dose in an extended release formulation.
 Give additive effect of used both the drugs.
 Hence reduce dose dependent side -effects. Also, Ondansetron is
able to overcome the some side effects of Capacetabine.
 The process involves reduced manufacturing steps and
manufacturing time and finally makes a cost effective formulation
1. AIM OF PRESENT WORK
2. BILAYER TABLET
 Bi-layer tablet which is made up of two Distinct
layers. compressed together with the individual
layers lying one on top of Another.
 The administration of sustained release preparation
as one layer with the immediate release preparation
as the second layer is possible. The separation of
two incompatible substances with addition of any
barrier layer between them is possible.
 DUal RElease Drug Absorption System
 (DUREDAS technology) is a bilayer tablet which can
provide immediate or sustained release of two drugs
or different release rates of the same drug in one
dosage form.
3. LITERATURE REVIEW
Researcher Research Title
M.Sowmya, M.Saritha
Has developed and optimized bilayered sustained
release matrix tablets of Valsartan.
Pandey H developed sustained release bilayer tablet of
domperidone using hydrophilic matrix material such
as HPMC, carbapol and poly-ethylene oxide.
Shirwaikar A. formulated sustained release of Diltiazem
hydrochloride tablets by utilizing the bilayer
concept using matrix material rosin and ethyl
cellulose.
Bhavesh Shiyani et
al.
The aim of this study was to prepare bi-layer tablet
of Metoclopramide Hydrochloride (MTH) and
Ibuprofen (IB) for the effective treatment of
migraine.
Jayabalan Nirmal et
al
formulated bilayer tablets consisting of
atorvastatin calcium (AT) as an immediate
release layer and nicotinic acid (NA) as an
extended release layer.
4. PLAN OF WORK
Pre-formulation studies
 Calibration curve.
 Flow properties.
 Drug excipient compatibilities.
 Preparation Of Tablets By Direct Compression Method ( IR
tablets).
 Preparation Of Tablets By Direct Compression Method (SR
tablets).
 Evaluation of the prepared tablets for various physico-
chemical parameters such as.
 Appearance.
 Hardness.
 Weight variation.
 Friability.
 Thickness.
 In vitro drug release.
 Kinetic studies.
4.DRUG PROFILE
Name Capacetabine
Brand names Xeloda
Categories
 Antineoplastic
 Antimetabolites
Indication For the treatment of patients with metastatic breast cancer
resistant to both paclitaxel and an anthracycline-containing
chemotherapy regimen.
Plasma Half life Capacetabine having shorter half life, 45-60 minutes and its
metabolites.
Mechanism of action Folate cofactor, N5-10-methylenetetrahydrofolate, bind to
thymidylate synthase (TS) to form a covalently bound
ternary complex. This binding inhibits the formation of
thymidylate from 2'-deaxyuridylate.
Absorption Readily absorbed through the GI tract (~70%).
Properties:
State
melting point
Solid
110-121 °C
polarizability 35.81
Dosage forms Tablet oral
4.DRUG PROFILE
Name Ondansetron
Description A competitive serotonin type 3 receptor antagonist. It is
effective in the treatment of nausea and vomiting caused by
cytotoxic chemotherapy drugs.
Category Antiemetics
Indication For the prevention of nausea and vomiting associated with
emetogenic cancer chemotherapy, postoperation, and
radiation.
Mechanism
of action
Ondansetron is a selective serotonin 5-HT3 receptor antagonist.
The antiemetic activity of the drug is brought about through
the inhibition of 5-HT3 receptors present both centrally
(medullary chemoreceptor zone) and peripherally (GI tract).
Absorption
Ondansetron is well absorbed after oral administration and
undergoes limited first-pass metabolism.
Protein binding 70%-76% (Plasma protein binding)
Half life 5.7 hours
State solid
EXCIPIENTS
POVIDONE Enhancer; tablet Disintegrant;
dissolution binder.
MAGNESIUM STEARATE Tablet and capsule lubricant .
CROSS POVIDONE (CP) Tablet disintegrant. and dissolution
agent.
SODIUM STARCH GLYCOLATE
(SSG)
Tablet and capsule disintegrant.
Microcrystalline cellulose (MCC) Adsorbent; suspending agent; tablet
and capsule diluent; tablet
disintegrant.
Hydroxy Propyl Methyl Cellelose
(HPMC) Minimize interaction problems when
used in acidic, basic,
Polyvinyle pyrrolydine (PVP)
Binder in wet granulation
Ethyl Cellelose (EC)
Coating agent,
Sodium Lauryl Sulphate (SLS)
Excipient in dissolvable dosage forms.
Talc Lubricant
5.PREFORMULATION & FORMULATIONS STUDY
.PREFORMULATION STUDY:
◦ Organoleptic properties
◦ Solubility
◦ Density
◦ Carr’s compressibility index & Hausner’s ratio
◦ Angle of repose(ɵ)
◦ Compatibility studies
◦ F.T.I.R
 FORMULATIONS
 The bilayer tablet was prepared by direct compression method.
 As shown in Table powder mixtures of Capacetabine,
microcrystalline cellulose, polymers and binder were dry
blended for 20 min followed by addition of Magnesium Stearate
and Talc.
 The mixtures were then further blended for 10 min., 400mg of
resultant powder blend was manually compressed using KBr
hydraulic press at a pressure of 1 ton, with a 12mm punch and
die to obtain the tablet.
a) First layer fill ; b) First layer tamping;
c) Upper punch withdrawal; d) second layer fill;
e) main compression; f) Ejection;
Ingredien
ts
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Capacetabi
ne (mg)
150 150 150 150 150 150 150 150 150 150
HPMC
K4M(%)
10 -- -- -- -- -- 5 -- -- --
HPMC
K100M(%)
-- 10 -- -- 15 20 15 15 15 20
HPMC E15
(%)
-- -- 10 -- -- -- -- 5 -- --
EC(%) -- -- -- 10 -- -- -- -- 5 5
PVP K30
(%)
5 5 5 5 5 5 5 5 5 5
Talc (%) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
Magnesium
stearate(%
)
2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
MCC(mg) Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S
Total
weight
(mg)
400 400 400 400 400 400 400 400 400 400
COMPOSITION OF SUSTAINED RELEASE LAYER
Table no 1 formulation table for sustained release layer
5.PREFORMULATION & FORMULATIONS STUDY
 DIRECT COMPRESSION FOR IMMEDIATE LAYER
All the ingredients were passed through sieve and
mixed in a motor and pestle for 30min for uniform
mixing. The addition of ingredients was done in a
geometrical manner. Then the ondansetron layer was
compressed using 8mm round punch.
COMPOSITION OF IMMEDIATE RELEASE LAYER
Table no2: formulation table for immediate release layer
Ingredi
ents
(mg)
F1 F2 F3 F4 F5 F6 F7 F8 F9
Ondans
etron
8 8 8 8 8 8 8 8 8
HPC
(%)
5 5 5 5 5 5 5 5 5
SSG(%) 5 -- -- -- -- -- -- -- --
CCS(%) -- 5 -- 7.5 10 12.5 10 10 10
CP(%) -- -- 5 -- -- -- -- -- --
Lactose
monohy
drate
Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S
Magnesi
um
stearate
(%)
2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
Talc
(%)
2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
SLS(%) -- -- -- -- -- -- 0.5 1 1.5
BILAYERED TABLET PUNCH
After the batch was optimized in both immediate release layer ( F8) and
sustained release layer (F7).The optimized batch in both was
compressed by using same ingredients
Flow Properties
Angle of Repose
Bulk density:
Tapped density
Compressibility index and Hausner ratio
TABLE NO 3 : ACCEPTANCE CRITERIA OF FLOW PROPERTIES
Flow properties Angle of repose(θ) Compressibility
Index (%)
Hausner ratio
Excellent 25-30 <10 1.00-1.11
Good 31-35 11-15 1.12-1.18
Fair 36-40 16-20 1.19-1.25
Passable 41-45 21-25 1.26-1.34
Poor 46-55 26-31 1.35-1.45
Very poor 56-65 32-37 1.46-1.59
Very very poor > 66 >38 >1.6
EVALUATION’S PARAMETERS
 Appearance
 Weight variation test
 Thickness test
 Hardness test
 Friability test
 Development of analytical methods
 In-vitro studies
 Swelling index
 Drug content(assay of tablet)
 Release of kinetics
 Stability study
6. RESULT & DISCUSSION
 Pre-compression parameters:
 Preformulation studies:
 Capacetabine(API)
 Physical characterization:
 physical characterization of Capacetabine was
studied.
 Density and flow properties of drug:
the drug having the excellent flow properties.
 Evaluation of Formulated blend: Bulk density,
Tapped density, Carr’s compressibility index ,
Hausner’s ratio and Angle of repose are
studied .the values are within the limits. And
the Formulation blend was good flow property
6. RESULT & DISCUSSION
 Preparation of standard calibration
curve of Ondansetron: in 0.1N HCl
calibration curve of Ondansetron in 0.1N HCl
 Standard Graph of Capacetabine (0.1 N
Hcl):
calibration curve for Capacetabine in 0.1N HCl
at 303nm
 Standard Graph of Capacetabine in
6.8pH phosphate buffer :
calibration curve for capacetabine in 6.8pH
phosphate buffer at 304nm
COMPATIBILITY STUDIES
 (FTIR) was used for infrared analysis of samples to intercept the
interactions of drug with polymers and other ingredients. The powder
sample along with KBr was used for FTIR studies. The samples were
analyzed between the wave numbers 4000 and 400 cm2.
 Fig no 1: FTIR spectra of Capecitabine pure drug
Fig no 2: FTIR spectra of Ondansetron pure drug
Fig no 3: FTIR spectra of bilayered tablet
EVALUATION OF PRE COMPRESSION PARAMETERS FOR
SUSTAINED RELAESE LAYER OF CAPACETABINE
 Formulations
 Angle of Repose (θ)
 Loose Bulk
 Density (g/ml)
 Tapped Bulk
 Density (g/ml) %
 Compressibility
 Hausner’s ratio
 INVITRO DISSOLUTION STUDIES FOR SR TABLETS -
 DISSOLUTION STUDY ( SR TABLETS) :
 Acidic Stage:
 Medium : 0.1N HCL
 Type of apparatus : USP - II (paddle type)
 RPM : 50
 Volume : 900ml
 Temperature : 37ºC± 0.5
 Time : 2hrs
 Buffer Stage:
 Medium : 6.8pH phosphate buffer
 Type of apparatus : USP - II (paddle type)
 RPM : 50
 Volume : 900ml
 Time : 24hrs
 In vitro dissolution for SR tablets were done initially in 0.1N HCL for 2hrs
and next in 6.8 phosphate buffer for 12hrs
In-Vitro Drug Release Studies for SR tablets:
Table no 4. Cumulative Percentage Drug Release of Sustained Layer
Time
(hrs)
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Dissolution medium 0.1N HCL
1 38.5 45.9 80.4 32.4 25.5 19.6 25.5 34.5 35.6 26.3
2 45.7 72.2 95.6 45.5 39.9 24.3 39.2 42.1 40 33.2
6.8pH phosphate buffer
3 53.8 80.7 -- 67.4 43.4 31.4 46.5 52.7 49.7 40.1
4 70.4 92.4 -- 72.6 59.4 45.9 55.2 60.3 53.9 45.6
5 84.9 -- -- 85.4 78.2 57.3 68.5 72.4 63.8 55.2
6 93.6 -- -- 95.8 94.2 80.7 75.9 78.3 70.4 63.8
8 -- -- -- -- -- 94.9 81.3 80.1 75.8 73.6
12 -- -- -- -- -- -- 96.5 -- 84.9 80.4
Dissolution Medium for SR tablets
Table no 5: Dissolution profile of bilayered tablet
S.NO Sampling time
Percentage drug released (%)
ONDANSETRAN CAPACETABINE
1 15mins 80.7 4.2
2 30 mins 99.8 6.6
3 1hr -- 20.6
4 2hr -- 37.7
5 3hr -- 45.4
6 4hr -- 53.8
7 5hr -- 69.7
8 6hr -- 77.9
9 8hr -- 89.0
10 12hr -- 97.3Discussion for in-vitro release of Capacetabine layer SR
From the table, it was confirmed that the F1, F2, F3, F4, F5, F6 and F8 of SR layer
does not fulfill the sustained release theory up to 12 hrs. And also from the table,
it was also confirmed that the formulation made with combination of HPMC K100
and HPMC K4M (F7) showed maximum drug release up to 12hrs.
 KINETIC RELEASE MODELS:
 Drug release kinetics and mechanism:
 To analyze the mechanism of drug releasefrom
the formulation, the dissolution profile of all
the batches were fitted to zero order, first
order, Higuchi and Peppas models to ascertain
the kinetic modeling of drug release.
• Zero Order: Q = K0 t
• First order: Log Qt = Log Qo+ K1t /
2.303
• Peppas model: Mt/M∞ = ktn
Higuichi model: Q = K2 t1/2
y = 1.523x + 0.6649
R² = 0.6341
0
0.5
1
1.5
2
2.5
0 0.2 0.4 0.6 0.8 1 1.2
L
O
G
%
C
D
R
LOG TIME
PEPPAS
y = 8.1531x + 15.432
R² = 0.8791
0
20
40
60
80
100
120
0 5 10 15
%
C
D
R
TIME IN HRS
ZERO ORDER
Fig no 5 - kinetic release graph for F7 sustained release formulation
Table no 6:
 EVALUATION PARAMETERS FOR IMMEDIATE RELEASE
LAYER OF ONDANSETRANPRE COMPRESSION
PARAMETERSFormulation
s
Angle of
Repose (θ)
Loose Bulk
Density
(g/ml)
Tapped Bulk
Density
(g/ml)
%
Compressibil
ity
Hausner’s
ratio
F1 23.90 0.3 0.35 14.29 1.17
F2 24.20 0.38 0.45 15.56 1.18
F3 27.20 0.53 0.62 14.52 1.17
F4 25.50 0.57 0.68 16.18 1.19
F5 23.80 0.43 0.49 12.24 1.14
F6 24.10 0.37 0.45 17.78 1.22
F7 29.40 0.43 0.5 14.00 1.16
F8 22.100 0.44 0.51 13.73 1.16
F9 26.40 0.4 0.47 14.89 1.18From the above pre-compression parameters it was clear
evidence that drug and excipients has good flow properties and
suitable for direct compression.
Post-compression parameters:
Post compression evaluation parameters for immediate
release formulation
 The results of the uniformity of weight, hardness,
thickness and friability of the tablets are given in
Table.
 All the tablets of different batches complied with the
official requirements of uniformity of weight as their
weights varied between 147 to 152mg.
 The hardness of the tablets ranged from 3.1 to
3.6kg/cm2 and the friability values were less than
0.5% indicating that the matrix tablets were compact
and hard.
 The thickness of the tablets ranged from to 2.1 to
2.5mm. Thus all the physical attributes of the prepared
tablets were found be practically within control.
Table no 7. Post compression parameters for
immediate release tablets
Formulation
s
Average weight
(mg)
Hardness
Kg/cm2
Thickness
(mm)
Friability (%)
F1 149 3.4 2.1 0.29
F2 147 3.5 2.3 0.25
F3 150 3.1 2.5 0.30
F4 152 3.3 2.2 0.41
F5 150 3.6 2.4 0.52
F6 150 3.2 2.2 0.49
F7 148 3.1 2.5 0.44
F8 149 3.4 2.4 0.43
F9 150 3.3 2.3 0.42
Table No 8. Dissolution for immediate release
tablet of Ondansetran
Time
in
mins
F1 F2 F3 F4 F5 F6 F7 F8 F9
5 25 22 14 22 36 31 40 65 48
10 37 38 26 42 57 59 67 70 63
15 45 49 40 56 65 65 79 84 80
30 50 56 54 63 72 72 86 96 94
45 48 72 63 78 88 86 94 -- --
60
62 80 75 89 93 95
--
-- --
BILAYERED TABLET COMPRESSION
 After the batch was optimized in both immediate release layer (F8) and sustained release
layer (F7).The optimized batch in both was compressed by using same ingredients.
 DISSOLUTION STUDY (BILAYERED TABLETS) :
 Dissolution Medium for IR tablets
 Acidic Stage:
 Medium : 0.1N HCL
 Type of apparatus : USP - II (paddle type)
 RPM : 50
 Volume : 900ml
 Temperature : 37ºC± 0.5
 Time : 30min
In vitro dissolution for IR tablets were done in 0.1N HCL for 30 minutes.
 Dissolution Medium for SR tablets
 Acidic Stage:
 Medium : 0.1N HCL
 Type of apparatus : USP - II (paddle type)
 RPM : 50
 Volume : 900ml
 Temperature : 37ºC± 0.5
 Time : 2hrs
 In vitro dissolution for SR tablets were done in 6.8 pH for 12hrs.
Table no 9 : Dissolution profile of bilayered tablet
S.NO Sampling time
Percentage drug released (%)
ONDANSETRAN CAPACETABINE
1 15mins 80.7 4.2
2 30 mins 99.8 6.6
5 1hr -- 20.6
6 2hr -- 37.7
7 3hr -- 45.4
8 4hr -- 53.8
9 5hr -- 69.7
10 6hr -- 77.9
11 8hr -- 89.0
12 12hr -- 97.3
Stability Studies
 Stability of a drug has been defined as the ability of a particular formulation, in
a specific container, to remain within its physical, chemical, therapeutic and
toxicological specifications.
 The purpose of stability testing is to provide evidence on how the quality of a
drug substance or drug product varies with time under
the influence of a variety of environmental factors such as
temperature, humidity, light, and enables recommended
storage conditions.
 Overall observations from different evaluation studies such as drug-polymer
interactions, evaluation of prepared formulations and drug release studies
were carried out.
 Based on the obtained results best formulation was subjected for further
stability study.
 The stability study was conducted as per ICH guidelines for the period of six
months at various accelerated temperature and humidity conditions of
25°C/65%RH, 40°C/75%RH.
 The accelerated stability study of the best formulations was carried out as per
the ICH guidelines
Table 10 :STABILITY DATA OF OPTIMIZED FORMULATION
S.No
Time points
(min)
Initial
Cumulative % Drug Release (mean SD) (n=3)
25C/60%RH 40C/75%RH
1st Month 3rd Month 1stMonth
3rd
Month
1
0.5 99.8
99.4 98.2 98.0 97.7
2
1
20.6 20.1 19.8 20.5 19.1
3
2
37.7 35.1 35.0 34.8 34.2
4
3
45.4 45.2 44.7 45.0 44.6
5
4
53.8 52.1 51.9 50.5 50.7
6
5
69.7 67.2 67.1 66.7 66.2
7 6 77.9 77.1 76.3 77.2 76.1
8 8 89.0 88.8 87.4 88.4 86.4
9 Assay 99.7 99.3 99.4 99.2 98.7
SUMMARY & CONCLUSION
 The Bilayered tablets containing Capacetabine SR and
Ondansetron IR were successfully prepared by direct
compression method respectively.
 Various formulations were prepared and evaluated with an
aim of presenting Capacetabine as sustained release and
Ondansetron as immediate release for improving the patient’s
compliance.
 The physiochemical evaluation results for the granules of all
trials pass the official limits in angle of repose,
compressibility index.
 The prepared blend for IR layer tablets and SR layer tablets
were also maintained the physiochemical properties of tablets
such as thickness, hardness, weight variation, friability.
 The optimized formulation F8 in IR formulations contains the
average thickness of 2.4mm, average hardness of 3.4 kg/cm2,
average weight of 149mg, friability of 0.43%.
SUMMARY & CONCLUSION
 The optimized formulation F7 in SR formulations contains the
average thickness of 2.3mm, average hardness of 7.3 kg/cm2,
friability of 0.41%.
 The F7 formulation which releases the capacetabine in sustained
manner in 1st hour it releases 25.5% but the remaining drug
release was sustained up to 12 hours and ondansetron immediate
release F7 formulation showed 96 % drug release with in 30 min.
 With the data of kinetic analysis, F7 formulation showed best
linearity in Higuchi’s Equation plot indicating that the release of
drug from matrix tablet follows Non Fickian diffusion.
 The dissolution study was carried out for optimized bilayer tablet
and it correlates with the drug release of individual release layer
formulations.
“Hence it may be summarized that the tablets prepared by direct
compression method for sustained release layer and immediate
release layer might be a perfect and effective formulation to
prevent the side effects in treating cancer”.
BIBLIOGRAPHY
 AM raggi; R mandrioli; A ferranti; J. Pharm. Biomed. Analysis., 2003, 32, 1037-1044.
 Bhavesh shiyani, surendra gattani, and sanjay surana formulation and evaluation of bi-
layer tablet of metoclopramide hydrochloride and ibuprofen .Aaps pharma
scitech.Sep2008;9(3) 818-827.
 Chien yw. Controlled and modulated release drug delivery system in swarbrik J, boylan JC
(eds.). Encyclopaedia of pharmaceutical technology, marcel dekker, new york, 1990: 281-
313.
 Chinam n, arethi b,pandith,singh p,maeduri v design and evaluation of sustained release
bilayer tablet of propranolol hydrochloride. Acta pharm.2007 aug 20;57:479-89.
 Deelip derle, omkar joshi, ashish pawar, jatin patel, amol jagadale formulation and
evaluation of buccoadhesive bi-layer tablet of propranolol hydrochloride. International
journal of pharmacy and pharmaceutical sciences, vol. 1, issue 1, july-sep. 2009
 E rippe. Compression of solids and compressed dosage forms. In: encyclopedia of
 Girish S. Sonara, devendra K. Jaina, dhananjay M. More preparation and in vitro evaluation
of bilayer and fl oating-bioadhesive tablets of rosiglitazone maleate. Bilayer and floating-
bioadhesive tablets of rosiglitazone maleate/asian journal of pharmaceutical sciences 2007,
2 (4): 161-169.
 Grabowski sr. Principles of anatomy and physiology. 10th ed. New york:john willey and
sons; 2002: 866-873.
 Indian pharmacopoeia. Vol. II, 4th ed. Thecontroller of publications, new delhi,1996, p736
 J siepmann; H kranz; R bodmeier; NA peppas; pharm res., 1999, 16, 1748-1756.
 Kulkarni a, bhatia m development and evaluation of regioselective bilayer floating tablets
of atenolol and lovastatin to give immediate release of lovastatin and sustained release of
atenolol.Iranian journal of pharm,research. 2009 june 8(1):15-25.
 Silvina ab, maria cl, claudio js. In-vitro studies of diclofenac sodium controlled-
release from biopolymeric hydrophilic matrices. J pharm pharmaceut sci.
2002;5(3):213-219.
 Talwar n, sen h, staniforth jn, inventors. Orally administered controlled drug
delivery system providing temporal and spatial control. Jul 2001. Us patent 6261
601.
 The united states pharmacopoeia. 29th edn., Asian edition. Rockville, md: usp
conventional inc: 2006, 2673-2680.
 Tripathi kd. Essentials of medical pharmacology, 2009, 6th edition, pg 627-651.
 Upendra kumar sharma , himanshu pandey and avinash chandra pandey.
Controlled release of an anti- emetic agent from a polymeric matrix: formulation
and in-
 Valentina r, alberto r, giorgio r, monica c. Increased absorption rate of diclofenac
from fast acting formulation containing its potassium salt. Arzneimittel-forschung
2001;51(11):885-90.
 Vishnu m patel., Bhupendra g. Et al mucoadhesive bilayer tablets of propranolol
hydrochloride. Aaps pharmscitech. Sep 2007; 8(3): e203–e208.
 Vishnu m. Patel,1 bhupendra g. Prajapati,1 and madhabhai m. Patel formulation,
evaluation, and comparison of bilayered and multilayered mucoadhesive buccal
devices of propranolol hydrochloride. Aaps pharmscitech 2007; 8 (1) article 22
(http://www.Aapspharmscitech.Org).
 Vitro study. Pandey et al., Ijpsr, 2011; vol. 2(10): 2746-2749 .
 Yassin el-said hamza and mona hassan aburahma design and in vitro evaluation
of novel sustained-release double-layer tablets of lornoxicam: utility of
cyclodextrin and xanthan gum combination. Aaps pharmscitech. 2009 dec
Thank you
Reg.261311006

More Related Content

What's hot

DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATE
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATEDEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATE
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATE
Ram C Dhakar
 
Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving TabletsFormulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Dr. Raghavendra Kumar Gunda
 
Design of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design Approach
Design of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design ApproachDesign of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design Approach
Design of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design Approach
Reshma Fathima .K
 
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...
ijperSS
 

What's hot (20)

formulation and evaluation of microbeads
formulation and evaluation of microbeadsformulation and evaluation of microbeads
formulation and evaluation of microbeads
 
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATE
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATEDEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATE
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATE
 
Preparation and evaluation of sustained release matrix tablets of Repaglinide...
Preparation and evaluation of sustained release matrix tablets of Repaglinide...Preparation and evaluation of sustained release matrix tablets of Repaglinide...
Preparation and evaluation of sustained release matrix tablets of Repaglinide...
 
Effect of diluent types and soluble diluents particle size on the dissolution...
Effect of diluent types and soluble diluents particle size on the dissolution...Effect of diluent types and soluble diluents particle size on the dissolution...
Effect of diluent types and soluble diluents particle size on the dissolution...
 
Calcium alginate beads
Calcium alginate beadsCalcium alginate beads
Calcium alginate beads
 
Development and Evaluation of Diclofenac Sodium Loaded Alginate Cross-Linking...
Development and Evaluation of Diclofenac Sodium Loaded Alginate Cross-Linking...Development and Evaluation of Diclofenac Sodium Loaded Alginate Cross-Linking...
Development and Evaluation of Diclofenac Sodium Loaded Alginate Cross-Linking...
 
Formulation and Evaluation of Pantoprazole Sodium Enteric Coated Tablets
Formulation and Evaluation of Pantoprazole Sodium Enteric Coated TabletsFormulation and Evaluation of Pantoprazole Sodium Enteric Coated Tablets
Formulation and Evaluation of Pantoprazole Sodium Enteric Coated Tablets
 
Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using ...
Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using ...Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using ...
Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using ...
 
Advance Techniques of Bilayer tablet: A Review
Advance Techniques of Bilayer tablet: A ReviewAdvance Techniques of Bilayer tablet: A Review
Advance Techniques of Bilayer tablet: A Review
 
Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving TabletsFormulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
Formulation Development and Evaluation of Carbamazepine Fast Dissolving Tablets
 
Development and Evaluation of gastroretentive matrix tablets of Nateglinide
Development and Evaluation of gastroretentive matrix tablets of NateglinideDevelopment and Evaluation of gastroretentive matrix tablets of Nateglinide
Development and Evaluation of gastroretentive matrix tablets of Nateglinide
 
Formulation and evaluation of matrix type rosuvastatin sustained release tablets
Formulation and evaluation of matrix type rosuvastatin sustained release tabletsFormulation and evaluation of matrix type rosuvastatin sustained release tablets
Formulation and evaluation of matrix type rosuvastatin sustained release tablets
 
Bilayer Tablets of Aspirin and Atorvastatin
Bilayer Tablets of Aspirin and AtorvastatinBilayer Tablets of Aspirin and Atorvastatin
Bilayer Tablets of Aspirin and Atorvastatin
 
Formulation and Evaluation of Risperidone Fast Dissolving Tablets
Formulation and Evaluation of Risperidone Fast Dissolving TabletsFormulation and Evaluation of Risperidone Fast Dissolving Tablets
Formulation and Evaluation of Risperidone Fast Dissolving Tablets
 
SUSTAINED RELEASE BEADS
SUSTAINED RELEASE BEADS SUSTAINED RELEASE BEADS
SUSTAINED RELEASE BEADS
 
Design of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design Approach
Design of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design ApproachDesign of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design Approach
Design of Pulsatile Tablets of Pantoprazole Sodium: Factorial Design Approach
 
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...
 
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...
 
Preformulation by Dhiraj Shrestha
Preformulation by Dhiraj ShresthaPreformulation by Dhiraj Shrestha
Preformulation by Dhiraj Shrestha
 
srikanth final presentation
srikanth final presentationsrikanth final presentation
srikanth final presentation
 

Similar to Final project power point

Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...
Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...
Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...
Ajay Champaneri
 
FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...
FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...
FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...
Dhaneshwar P
 
Formulation development and evalution of matrix tablet of
Formulation development and evalution of matrix tablet ofFormulation development and evalution of matrix tablet of
Formulation development and evalution of matrix tablet of
Gajanan Ingole
 

Similar to Final project power point (20)

Formulation and evaluation of omeprazole floating tablets
Formulation and evaluation of omeprazole floating tabletsFormulation and evaluation of omeprazole floating tablets
Formulation and evaluation of omeprazole floating tablets
 
Blt PPT
Blt PPTBlt PPT
Blt PPT
 
METFORMIN HYDROCHLORIDE
METFORMIN HYDROCHLORIDE METFORMIN HYDROCHLORIDE
METFORMIN HYDROCHLORIDE
 
Synopsis copy
Synopsis   copySynopsis   copy
Synopsis copy
 
Formulation and evaluation of mucoadhesive tablets of carvedilol using natura...
Formulation and evaluation of mucoadhesive tablets of carvedilol using natura...Formulation and evaluation of mucoadhesive tablets of carvedilol using natura...
Formulation and evaluation of mucoadhesive tablets of carvedilol using natura...
 
Formulation and evaluation of sumatriptan succinate oral disintegrating table...
Formulation and evaluation of sumatriptan succinate oral disintegrating table...Formulation and evaluation of sumatriptan succinate oral disintegrating table...
Formulation and evaluation of sumatriptan succinate oral disintegrating table...
 
Pensee design and evaluation of ramipril 1
Pensee design and evaluation of ramipril 1Pensee design and evaluation of ramipril 1
Pensee design and evaluation of ramipril 1
 
Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...
Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...
Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatrip...
 
FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...
FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...
FORMULATION, EVALUATION AND OPTIMISATION OF SUSTAINED RELEASE FLOATING BILAYE...
 
DEVELOPMENT AND VALIDATION OF CAPECITABINE TABLET (PHARMACEUTICAL DOSAGE FORM...
DEVELOPMENT AND VALIDATION OF CAPECITABINE TABLET (PHARMACEUTICAL DOSAGE FORM...DEVELOPMENT AND VALIDATION OF CAPECITABINE TABLET (PHARMACEUTICAL DOSAGE FORM...
DEVELOPMENT AND VALIDATION OF CAPECITABINE TABLET (PHARMACEUTICAL DOSAGE FORM...
 
Shivaji shinde colloquium ppt..
Shivaji shinde colloquium ppt..Shivaji shinde colloquium ppt..
Shivaji shinde colloquium ppt..
 
Formulation and evaluation of Repaglinide biphasic mini tablets
Formulation and evaluation of Repaglinide biphasic mini tabletsFormulation and evaluation of Repaglinide biphasic mini tablets
Formulation and evaluation of Repaglinide biphasic mini tablets
 
THE JOURNAL CLUB- venkat m.pharm phramceutical analysis
THE JOURNAL CLUB- venkat m.pharm phramceutical analysisTHE JOURNAL CLUB- venkat m.pharm phramceutical analysis
THE JOURNAL CLUB- venkat m.pharm phramceutical analysis
 
Formulation development and evalution of matrix tablet of
Formulation development and evalution of matrix tablet ofFormulation development and evalution of matrix tablet of
Formulation development and evalution of matrix tablet of
 
Method development and validation for the simultaneous estimation of saxaglip...
Method development and validation for the simultaneous estimation of saxaglip...Method development and validation for the simultaneous estimation of saxaglip...
Method development and validation for the simultaneous estimation of saxaglip...
 
Formulation and evaluation of Gastroretentive Bosentan monohydrate tablets us...
Formulation and evaluation of Gastroretentive Bosentan monohydrate tablets us...Formulation and evaluation of Gastroretentive Bosentan monohydrate tablets us...
Formulation and evaluation of Gastroretentive Bosentan monohydrate tablets us...
 
Formulation and invitro evaluation of gastro retentive floating mini tablets ...
Formulation and invitro evaluation of gastro retentive floating mini tablets ...Formulation and invitro evaluation of gastro retentive floating mini tablets ...
Formulation and invitro evaluation of gastro retentive floating mini tablets ...
 
Methyl phenidate
Methyl phenidate Methyl phenidate
Methyl phenidate
 
Development and characterization of porous starch curcumin solid dispertion...
Development and characterization of  porous starch  curcumin solid dispertion...Development and characterization of  porous starch  curcumin solid dispertion...
Development and characterization of porous starch curcumin solid dispertion...
 
Analytical method development and validation for the estimation of quinapril ...
Analytical method development and validation for the estimation of quinapril ...Analytical method development and validation for the estimation of quinapril ...
Analytical method development and validation for the estimation of quinapril ...
 

Recently uploaded

ppt your views.ppt your views of your college in your eyes
ppt your views.ppt your views of your college in your eyesppt your views.ppt your views of your college in your eyes
ppt your views.ppt your views of your college in your eyes
ashishpaul799
 

Recently uploaded (20)

Features of Video Calls in the Discuss Module in Odoo 17
Features of Video Calls in the Discuss Module in Odoo 17Features of Video Calls in the Discuss Module in Odoo 17
Features of Video Calls in the Discuss Module in Odoo 17
 
The Benefits and Challenges of Open Educational Resources
The Benefits and Challenges of Open Educational ResourcesThe Benefits and Challenges of Open Educational Resources
The Benefits and Challenges of Open Educational Resources
 
Basic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
Basic Civil Engg Notes_Chapter-6_Environment Pollution & EngineeringBasic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
Basic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
 
ppt your views.ppt your views of your college in your eyes
ppt your views.ppt your views of your college in your eyesppt your views.ppt your views of your college in your eyes
ppt your views.ppt your views of your college in your eyes
 
Telling Your Story_ Simple Steps to Build Your Nonprofit's Brand Webinar.pdf
Telling Your Story_ Simple Steps to Build Your Nonprofit's Brand Webinar.pdfTelling Your Story_ Simple Steps to Build Your Nonprofit's Brand Webinar.pdf
Telling Your Story_ Simple Steps to Build Your Nonprofit's Brand Webinar.pdf
 
Exploring Gemini AI and Integration with MuleSoft | MuleSoft Mysore Meetup #45
Exploring Gemini AI and Integration with MuleSoft | MuleSoft Mysore Meetup #45Exploring Gemini AI and Integration with MuleSoft | MuleSoft Mysore Meetup #45
Exploring Gemini AI and Integration with MuleSoft | MuleSoft Mysore Meetup #45
 
Mbaye_Astou.Education Civica_Human Rights.pptx
Mbaye_Astou.Education Civica_Human Rights.pptxMbaye_Astou.Education Civica_Human Rights.pptx
Mbaye_Astou.Education Civica_Human Rights.pptx
 
Capitol Tech Univ Doctoral Presentation -May 2024
Capitol Tech Univ Doctoral Presentation -May 2024Capitol Tech Univ Doctoral Presentation -May 2024
Capitol Tech Univ Doctoral Presentation -May 2024
 
Behavioral-sciences-dr-mowadat rana (1).pdf
Behavioral-sciences-dr-mowadat rana (1).pdfBehavioral-sciences-dr-mowadat rana (1).pdf
Behavioral-sciences-dr-mowadat rana (1).pdf
 
[GDSC YCCE] Build with AI Online Presentation
[GDSC YCCE] Build with AI Online Presentation[GDSC YCCE] Build with AI Online Presentation
[GDSC YCCE] Build with AI Online Presentation
 
Morse OER Some Benefits and Challenges.pptx
Morse OER Some Benefits and Challenges.pptxMorse OER Some Benefits and Challenges.pptx
Morse OER Some Benefits and Challenges.pptx
 
Navigating the Misinformation Minefield: The Role of Higher Education in the ...
Navigating the Misinformation Minefield: The Role of Higher Education in the ...Navigating the Misinformation Minefield: The Role of Higher Education in the ...
Navigating the Misinformation Minefield: The Role of Higher Education in the ...
 
“O BEIJO” EM ARTE .
“O BEIJO” EM ARTE                       .“O BEIJO” EM ARTE                       .
“O BEIJO” EM ARTE .
 
factors influencing drug absorption-final-2.pptx
factors influencing drug absorption-final-2.pptxfactors influencing drug absorption-final-2.pptx
factors influencing drug absorption-final-2.pptx
 
An Overview of the Odoo 17 Discuss App.pptx
An Overview of the Odoo 17 Discuss App.pptxAn Overview of the Odoo 17 Discuss App.pptx
An Overview of the Odoo 17 Discuss App.pptx
 
INU_CAPSTONEDESIGN_비밀번호486_업로드용 발표자료.pdf
INU_CAPSTONEDESIGN_비밀번호486_업로드용 발표자료.pdfINU_CAPSTONEDESIGN_비밀번호486_업로드용 발표자료.pdf
INU_CAPSTONEDESIGN_비밀번호486_업로드용 발표자료.pdf
 
slides CapTechTalks Webinar May 2024 Alexander Perry.pptx
slides CapTechTalks Webinar May 2024 Alexander Perry.pptxslides CapTechTalks Webinar May 2024 Alexander Perry.pptx
slides CapTechTalks Webinar May 2024 Alexander Perry.pptx
 
TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT VẬT LÝ 2024 - TỪ CÁC TRƯỜNG, TRƯ...
TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT VẬT LÝ 2024 - TỪ CÁC TRƯỜNG, TRƯ...TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT VẬT LÝ 2024 - TỪ CÁC TRƯỜNG, TRƯ...
TỔNG HỢP HƠN 100 ĐỀ THI THỬ TỐT NGHIỆP THPT VẬT LÝ 2024 - TỪ CÁC TRƯỜNG, TRƯ...
 
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
 
Championnat de France de Tennis de table/
Championnat de France de Tennis de table/Championnat de France de Tennis de table/
Championnat de France de Tennis de table/
 

Final project power point

  • 1. “DESIGN AND EVALUATION OF BILAYER TABLETS OF CAPECITABINE AND ONDANSETRON” Register number: 261311006 DEPARTMENT OF PHARMACEUTICS Under the guidance of CHERRAAN’S COLLEGE OF PHARMACY Dr. N. THIRUMOORTHY, COIMBATORE-641039 M. PHARM, PH.D.,
  • 2. It comprises of two layers, one of which is sustained release of Capacetabine and another one is immediate release of Ondansetron. Hence, it uses Dual Release Drug Absorption System(DUREDAS) technology.  To provide once a day dosage form for the treatment of nausea and vomiting .  As Capacetabine having shorter half life, bilayer tablet provide extended release of Capacetabine .  Hence reduce dose frequency. Also, Ondansetron formulated as an immediate release part provides initial relief as is the case with loading dose in an extended release formulation.  Give additive effect of used both the drugs.  Hence reduce dose dependent side -effects. Also, Ondansetron is able to overcome the some side effects of Capacetabine.  The process involves reduced manufacturing steps and manufacturing time and finally makes a cost effective formulation 1. AIM OF PRESENT WORK
  • 3. 2. BILAYER TABLET  Bi-layer tablet which is made up of two Distinct layers. compressed together with the individual layers lying one on top of Another.  The administration of sustained release preparation as one layer with the immediate release preparation as the second layer is possible. The separation of two incompatible substances with addition of any barrier layer between them is possible.  DUal RElease Drug Absorption System  (DUREDAS technology) is a bilayer tablet which can provide immediate or sustained release of two drugs or different release rates of the same drug in one dosage form.
  • 4. 3. LITERATURE REVIEW Researcher Research Title M.Sowmya, M.Saritha Has developed and optimized bilayered sustained release matrix tablets of Valsartan. Pandey H developed sustained release bilayer tablet of domperidone using hydrophilic matrix material such as HPMC, carbapol and poly-ethylene oxide. Shirwaikar A. formulated sustained release of Diltiazem hydrochloride tablets by utilizing the bilayer concept using matrix material rosin and ethyl cellulose. Bhavesh Shiyani et al. The aim of this study was to prepare bi-layer tablet of Metoclopramide Hydrochloride (MTH) and Ibuprofen (IB) for the effective treatment of migraine. Jayabalan Nirmal et al formulated bilayer tablets consisting of atorvastatin calcium (AT) as an immediate release layer and nicotinic acid (NA) as an extended release layer.
  • 5. 4. PLAN OF WORK Pre-formulation studies  Calibration curve.  Flow properties.  Drug excipient compatibilities.  Preparation Of Tablets By Direct Compression Method ( IR tablets).  Preparation Of Tablets By Direct Compression Method (SR tablets).  Evaluation of the prepared tablets for various physico- chemical parameters such as.  Appearance.  Hardness.  Weight variation.  Friability.  Thickness.  In vitro drug release.  Kinetic studies.
  • 6. 4.DRUG PROFILE Name Capacetabine Brand names Xeloda Categories  Antineoplastic  Antimetabolites Indication For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. Plasma Half life Capacetabine having shorter half life, 45-60 minutes and its metabolites. Mechanism of action Folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Absorption Readily absorbed through the GI tract (~70%). Properties: State melting point Solid 110-121 °C polarizability 35.81 Dosage forms Tablet oral
  • 7. 4.DRUG PROFILE Name Ondansetron Description A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs. Category Antiemetics Indication For the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, postoperation, and radiation. Mechanism of action Ondansetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). Absorption Ondansetron is well absorbed after oral administration and undergoes limited first-pass metabolism. Protein binding 70%-76% (Plasma protein binding) Half life 5.7 hours State solid
  • 8. EXCIPIENTS POVIDONE Enhancer; tablet Disintegrant; dissolution binder. MAGNESIUM STEARATE Tablet and capsule lubricant . CROSS POVIDONE (CP) Tablet disintegrant. and dissolution agent. SODIUM STARCH GLYCOLATE (SSG) Tablet and capsule disintegrant. Microcrystalline cellulose (MCC) Adsorbent; suspending agent; tablet and capsule diluent; tablet disintegrant. Hydroxy Propyl Methyl Cellelose (HPMC) Minimize interaction problems when used in acidic, basic, Polyvinyle pyrrolydine (PVP) Binder in wet granulation Ethyl Cellelose (EC) Coating agent, Sodium Lauryl Sulphate (SLS) Excipient in dissolvable dosage forms. Talc Lubricant
  • 9. 5.PREFORMULATION & FORMULATIONS STUDY .PREFORMULATION STUDY: ◦ Organoleptic properties ◦ Solubility ◦ Density ◦ Carr’s compressibility index & Hausner’s ratio ◦ Angle of repose(ɵ) ◦ Compatibility studies ◦ F.T.I.R  FORMULATIONS  The bilayer tablet was prepared by direct compression method.  As shown in Table powder mixtures of Capacetabine, microcrystalline cellulose, polymers and binder were dry blended for 20 min followed by addition of Magnesium Stearate and Talc.  The mixtures were then further blended for 10 min., 400mg of resultant powder blend was manually compressed using KBr hydraulic press at a pressure of 1 ton, with a 12mm punch and die to obtain the tablet.
  • 10. a) First layer fill ; b) First layer tamping; c) Upper punch withdrawal; d) second layer fill; e) main compression; f) Ejection;
  • 11. Ingredien ts F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 Capacetabi ne (mg) 150 150 150 150 150 150 150 150 150 150 HPMC K4M(%) 10 -- -- -- -- -- 5 -- -- -- HPMC K100M(%) -- 10 -- -- 15 20 15 15 15 20 HPMC E15 (%) -- -- 10 -- -- -- -- 5 -- -- EC(%) -- -- -- 10 -- -- -- -- 5 5 PVP K30 (%) 5 5 5 5 5 5 5 5 5 5 Talc (%) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Magnesium stearate(% ) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 MCC(mg) Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Total weight (mg) 400 400 400 400 400 400 400 400 400 400 COMPOSITION OF SUSTAINED RELEASE LAYER Table no 1 formulation table for sustained release layer
  • 12. 5.PREFORMULATION & FORMULATIONS STUDY  DIRECT COMPRESSION FOR IMMEDIATE LAYER All the ingredients were passed through sieve and mixed in a motor and pestle for 30min for uniform mixing. The addition of ingredients was done in a geometrical manner. Then the ondansetron layer was compressed using 8mm round punch. COMPOSITION OF IMMEDIATE RELEASE LAYER
  • 13. Table no2: formulation table for immediate release layer Ingredi ents (mg) F1 F2 F3 F4 F5 F6 F7 F8 F9 Ondans etron 8 8 8 8 8 8 8 8 8 HPC (%) 5 5 5 5 5 5 5 5 5 SSG(%) 5 -- -- -- -- -- -- -- -- CCS(%) -- 5 -- 7.5 10 12.5 10 10 10 CP(%) -- -- 5 -- -- -- -- -- -- Lactose monohy drate Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Magnesi um stearate (%) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Talc (%) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 SLS(%) -- -- -- -- -- -- 0.5 1 1.5
  • 14. BILAYERED TABLET PUNCH After the batch was optimized in both immediate release layer ( F8) and sustained release layer (F7).The optimized batch in both was compressed by using same ingredients Flow Properties Angle of Repose Bulk density: Tapped density Compressibility index and Hausner ratio TABLE NO 3 : ACCEPTANCE CRITERIA OF FLOW PROPERTIES Flow properties Angle of repose(θ) Compressibility Index (%) Hausner ratio Excellent 25-30 <10 1.00-1.11 Good 31-35 11-15 1.12-1.18 Fair 36-40 16-20 1.19-1.25 Passable 41-45 21-25 1.26-1.34 Poor 46-55 26-31 1.35-1.45 Very poor 56-65 32-37 1.46-1.59 Very very poor > 66 >38 >1.6
  • 15. EVALUATION’S PARAMETERS  Appearance  Weight variation test  Thickness test  Hardness test  Friability test  Development of analytical methods  In-vitro studies  Swelling index  Drug content(assay of tablet)  Release of kinetics  Stability study
  • 16. 6. RESULT & DISCUSSION  Pre-compression parameters:  Preformulation studies:  Capacetabine(API)  Physical characterization:  physical characterization of Capacetabine was studied.  Density and flow properties of drug: the drug having the excellent flow properties.  Evaluation of Formulated blend: Bulk density, Tapped density, Carr’s compressibility index , Hausner’s ratio and Angle of repose are studied .the values are within the limits. And the Formulation blend was good flow property
  • 17. 6. RESULT & DISCUSSION  Preparation of standard calibration curve of Ondansetron: in 0.1N HCl calibration curve of Ondansetron in 0.1N HCl  Standard Graph of Capacetabine (0.1 N Hcl): calibration curve for Capacetabine in 0.1N HCl at 303nm  Standard Graph of Capacetabine in 6.8pH phosphate buffer : calibration curve for capacetabine in 6.8pH phosphate buffer at 304nm
  • 18. COMPATIBILITY STUDIES  (FTIR) was used for infrared analysis of samples to intercept the interactions of drug with polymers and other ingredients. The powder sample along with KBr was used for FTIR studies. The samples were analyzed between the wave numbers 4000 and 400 cm2.  Fig no 1: FTIR spectra of Capecitabine pure drug
  • 19. Fig no 2: FTIR spectra of Ondansetron pure drug
  • 20. Fig no 3: FTIR spectra of bilayered tablet
  • 21. EVALUATION OF PRE COMPRESSION PARAMETERS FOR SUSTAINED RELAESE LAYER OF CAPACETABINE  Formulations  Angle of Repose (θ)  Loose Bulk  Density (g/ml)  Tapped Bulk  Density (g/ml) %  Compressibility  Hausner’s ratio
  • 22.  INVITRO DISSOLUTION STUDIES FOR SR TABLETS -  DISSOLUTION STUDY ( SR TABLETS) :  Acidic Stage:  Medium : 0.1N HCL  Type of apparatus : USP - II (paddle type)  RPM : 50  Volume : 900ml  Temperature : 37ºC± 0.5  Time : 2hrs  Buffer Stage:  Medium : 6.8pH phosphate buffer  Type of apparatus : USP - II (paddle type)  RPM : 50  Volume : 900ml  Time : 24hrs  In vitro dissolution for SR tablets were done initially in 0.1N HCL for 2hrs and next in 6.8 phosphate buffer for 12hrs
  • 23. In-Vitro Drug Release Studies for SR tablets: Table no 4. Cumulative Percentage Drug Release of Sustained Layer Time (hrs) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 Dissolution medium 0.1N HCL 1 38.5 45.9 80.4 32.4 25.5 19.6 25.5 34.5 35.6 26.3 2 45.7 72.2 95.6 45.5 39.9 24.3 39.2 42.1 40 33.2 6.8pH phosphate buffer 3 53.8 80.7 -- 67.4 43.4 31.4 46.5 52.7 49.7 40.1 4 70.4 92.4 -- 72.6 59.4 45.9 55.2 60.3 53.9 45.6 5 84.9 -- -- 85.4 78.2 57.3 68.5 72.4 63.8 55.2 6 93.6 -- -- 95.8 94.2 80.7 75.9 78.3 70.4 63.8 8 -- -- -- -- -- 94.9 81.3 80.1 75.8 73.6 12 -- -- -- -- -- -- 96.5 -- 84.9 80.4
  • 24.
  • 25. Dissolution Medium for SR tablets Table no 5: Dissolution profile of bilayered tablet S.NO Sampling time Percentage drug released (%) ONDANSETRAN CAPACETABINE 1 15mins 80.7 4.2 2 30 mins 99.8 6.6 3 1hr -- 20.6 4 2hr -- 37.7 5 3hr -- 45.4 6 4hr -- 53.8 7 5hr -- 69.7 8 6hr -- 77.9 9 8hr -- 89.0 10 12hr -- 97.3Discussion for in-vitro release of Capacetabine layer SR From the table, it was confirmed that the F1, F2, F3, F4, F5, F6 and F8 of SR layer does not fulfill the sustained release theory up to 12 hrs. And also from the table, it was also confirmed that the formulation made with combination of HPMC K100 and HPMC K4M (F7) showed maximum drug release up to 12hrs.
  • 26.  KINETIC RELEASE MODELS:  Drug release kinetics and mechanism:  To analyze the mechanism of drug releasefrom the formulation, the dissolution profile of all the batches were fitted to zero order, first order, Higuchi and Peppas models to ascertain the kinetic modeling of drug release. • Zero Order: Q = K0 t • First order: Log Qt = Log Qo+ K1t / 2.303 • Peppas model: Mt/M∞ = ktn Higuichi model: Q = K2 t1/2
  • 27. y = 1.523x + 0.6649 R² = 0.6341 0 0.5 1 1.5 2 2.5 0 0.2 0.4 0.6 0.8 1 1.2 L O G % C D R LOG TIME PEPPAS y = 8.1531x + 15.432 R² = 0.8791 0 20 40 60 80 100 120 0 5 10 15 % C D R TIME IN HRS ZERO ORDER Fig no 5 - kinetic release graph for F7 sustained release formulation
  • 28. Table no 6:  EVALUATION PARAMETERS FOR IMMEDIATE RELEASE LAYER OF ONDANSETRANPRE COMPRESSION PARAMETERSFormulation s Angle of Repose (θ) Loose Bulk Density (g/ml) Tapped Bulk Density (g/ml) % Compressibil ity Hausner’s ratio F1 23.90 0.3 0.35 14.29 1.17 F2 24.20 0.38 0.45 15.56 1.18 F3 27.20 0.53 0.62 14.52 1.17 F4 25.50 0.57 0.68 16.18 1.19 F5 23.80 0.43 0.49 12.24 1.14 F6 24.10 0.37 0.45 17.78 1.22 F7 29.40 0.43 0.5 14.00 1.16 F8 22.100 0.44 0.51 13.73 1.16 F9 26.40 0.4 0.47 14.89 1.18From the above pre-compression parameters it was clear evidence that drug and excipients has good flow properties and suitable for direct compression.
  • 29. Post-compression parameters: Post compression evaluation parameters for immediate release formulation  The results of the uniformity of weight, hardness, thickness and friability of the tablets are given in Table.  All the tablets of different batches complied with the official requirements of uniformity of weight as their weights varied between 147 to 152mg.  The hardness of the tablets ranged from 3.1 to 3.6kg/cm2 and the friability values were less than 0.5% indicating that the matrix tablets were compact and hard.  The thickness of the tablets ranged from to 2.1 to 2.5mm. Thus all the physical attributes of the prepared tablets were found be practically within control.
  • 30. Table no 7. Post compression parameters for immediate release tablets Formulation s Average weight (mg) Hardness Kg/cm2 Thickness (mm) Friability (%) F1 149 3.4 2.1 0.29 F2 147 3.5 2.3 0.25 F3 150 3.1 2.5 0.30 F4 152 3.3 2.2 0.41 F5 150 3.6 2.4 0.52 F6 150 3.2 2.2 0.49 F7 148 3.1 2.5 0.44 F8 149 3.4 2.4 0.43 F9 150 3.3 2.3 0.42
  • 31. Table No 8. Dissolution for immediate release tablet of Ondansetran Time in mins F1 F2 F3 F4 F5 F6 F7 F8 F9 5 25 22 14 22 36 31 40 65 48 10 37 38 26 42 57 59 67 70 63 15 45 49 40 56 65 65 79 84 80 30 50 56 54 63 72 72 86 96 94 45 48 72 63 78 88 86 94 -- -- 60 62 80 75 89 93 95 -- -- --
  • 32. BILAYERED TABLET COMPRESSION  After the batch was optimized in both immediate release layer (F8) and sustained release layer (F7).The optimized batch in both was compressed by using same ingredients.  DISSOLUTION STUDY (BILAYERED TABLETS) :  Dissolution Medium for IR tablets  Acidic Stage:  Medium : 0.1N HCL  Type of apparatus : USP - II (paddle type)  RPM : 50  Volume : 900ml  Temperature : 37ºC± 0.5  Time : 30min In vitro dissolution for IR tablets were done in 0.1N HCL for 30 minutes.  Dissolution Medium for SR tablets  Acidic Stage:  Medium : 0.1N HCL  Type of apparatus : USP - II (paddle type)  RPM : 50  Volume : 900ml  Temperature : 37ºC± 0.5  Time : 2hrs  In vitro dissolution for SR tablets were done in 6.8 pH for 12hrs.
  • 33. Table no 9 : Dissolution profile of bilayered tablet S.NO Sampling time Percentage drug released (%) ONDANSETRAN CAPACETABINE 1 15mins 80.7 4.2 2 30 mins 99.8 6.6 5 1hr -- 20.6 6 2hr -- 37.7 7 3hr -- 45.4 8 4hr -- 53.8 9 5hr -- 69.7 10 6hr -- 77.9 11 8hr -- 89.0 12 12hr -- 97.3
  • 34. Stability Studies  Stability of a drug has been defined as the ability of a particular formulation, in a specific container, to remain within its physical, chemical, therapeutic and toxicological specifications.  The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, light, and enables recommended storage conditions.  Overall observations from different evaluation studies such as drug-polymer interactions, evaluation of prepared formulations and drug release studies were carried out.  Based on the obtained results best formulation was subjected for further stability study.  The stability study was conducted as per ICH guidelines for the period of six months at various accelerated temperature and humidity conditions of 25°C/65%RH, 40°C/75%RH.  The accelerated stability study of the best formulations was carried out as per the ICH guidelines
  • 35. Table 10 :STABILITY DATA OF OPTIMIZED FORMULATION S.No Time points (min) Initial Cumulative % Drug Release (mean SD) (n=3) 25C/60%RH 40C/75%RH 1st Month 3rd Month 1stMonth 3rd Month 1 0.5 99.8 99.4 98.2 98.0 97.7 2 1 20.6 20.1 19.8 20.5 19.1 3 2 37.7 35.1 35.0 34.8 34.2 4 3 45.4 45.2 44.7 45.0 44.6 5 4 53.8 52.1 51.9 50.5 50.7 6 5 69.7 67.2 67.1 66.7 66.2 7 6 77.9 77.1 76.3 77.2 76.1 8 8 89.0 88.8 87.4 88.4 86.4 9 Assay 99.7 99.3 99.4 99.2 98.7
  • 36. SUMMARY & CONCLUSION  The Bilayered tablets containing Capacetabine SR and Ondansetron IR were successfully prepared by direct compression method respectively.  Various formulations were prepared and evaluated with an aim of presenting Capacetabine as sustained release and Ondansetron as immediate release for improving the patient’s compliance.  The physiochemical evaluation results for the granules of all trials pass the official limits in angle of repose, compressibility index.  The prepared blend for IR layer tablets and SR layer tablets were also maintained the physiochemical properties of tablets such as thickness, hardness, weight variation, friability.  The optimized formulation F8 in IR formulations contains the average thickness of 2.4mm, average hardness of 3.4 kg/cm2, average weight of 149mg, friability of 0.43%.
  • 37. SUMMARY & CONCLUSION  The optimized formulation F7 in SR formulations contains the average thickness of 2.3mm, average hardness of 7.3 kg/cm2, friability of 0.41%.  The F7 formulation which releases the capacetabine in sustained manner in 1st hour it releases 25.5% but the remaining drug release was sustained up to 12 hours and ondansetron immediate release F7 formulation showed 96 % drug release with in 30 min.  With the data of kinetic analysis, F7 formulation showed best linearity in Higuchi’s Equation plot indicating that the release of drug from matrix tablet follows Non Fickian diffusion.  The dissolution study was carried out for optimized bilayer tablet and it correlates with the drug release of individual release layer formulations. “Hence it may be summarized that the tablets prepared by direct compression method for sustained release layer and immediate release layer might be a perfect and effective formulation to prevent the side effects in treating cancer”.
  • 38. BIBLIOGRAPHY  AM raggi; R mandrioli; A ferranti; J. Pharm. Biomed. Analysis., 2003, 32, 1037-1044.  Bhavesh shiyani, surendra gattani, and sanjay surana formulation and evaluation of bi- layer tablet of metoclopramide hydrochloride and ibuprofen .Aaps pharma scitech.Sep2008;9(3) 818-827.  Chien yw. Controlled and modulated release drug delivery system in swarbrik J, boylan JC (eds.). Encyclopaedia of pharmaceutical technology, marcel dekker, new york, 1990: 281- 313.  Chinam n, arethi b,pandith,singh p,maeduri v design and evaluation of sustained release bilayer tablet of propranolol hydrochloride. Acta pharm.2007 aug 20;57:479-89.  Deelip derle, omkar joshi, ashish pawar, jatin patel, amol jagadale formulation and evaluation of buccoadhesive bi-layer tablet of propranolol hydrochloride. International journal of pharmacy and pharmaceutical sciences, vol. 1, issue 1, july-sep. 2009  E rippe. Compression of solids and compressed dosage forms. In: encyclopedia of  Girish S. Sonara, devendra K. Jaina, dhananjay M. More preparation and in vitro evaluation of bilayer and fl oating-bioadhesive tablets of rosiglitazone maleate. Bilayer and floating- bioadhesive tablets of rosiglitazone maleate/asian journal of pharmaceutical sciences 2007, 2 (4): 161-169.  Grabowski sr. Principles of anatomy and physiology. 10th ed. New york:john willey and sons; 2002: 866-873.  Indian pharmacopoeia. Vol. II, 4th ed. Thecontroller of publications, new delhi,1996, p736  J siepmann; H kranz; R bodmeier; NA peppas; pharm res., 1999, 16, 1748-1756.  Kulkarni a, bhatia m development and evaluation of regioselective bilayer floating tablets of atenolol and lovastatin to give immediate release of lovastatin and sustained release of atenolol.Iranian journal of pharm,research. 2009 june 8(1):15-25.
  • 39.  Silvina ab, maria cl, claudio js. In-vitro studies of diclofenac sodium controlled- release from biopolymeric hydrophilic matrices. J pharm pharmaceut sci. 2002;5(3):213-219.  Talwar n, sen h, staniforth jn, inventors. Orally administered controlled drug delivery system providing temporal and spatial control. Jul 2001. Us patent 6261 601.  The united states pharmacopoeia. 29th edn., Asian edition. Rockville, md: usp conventional inc: 2006, 2673-2680.  Tripathi kd. Essentials of medical pharmacology, 2009, 6th edition, pg 627-651.  Upendra kumar sharma , himanshu pandey and avinash chandra pandey. Controlled release of an anti- emetic agent from a polymeric matrix: formulation and in-  Valentina r, alberto r, giorgio r, monica c. Increased absorption rate of diclofenac from fast acting formulation containing its potassium salt. Arzneimittel-forschung 2001;51(11):885-90.  Vishnu m patel., Bhupendra g. Et al mucoadhesive bilayer tablets of propranolol hydrochloride. Aaps pharmscitech. Sep 2007; 8(3): e203–e208.  Vishnu m. Patel,1 bhupendra g. Prajapati,1 and madhabhai m. Patel formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride. Aaps pharmscitech 2007; 8 (1) article 22 (http://www.Aapspharmscitech.Org).  Vitro study. Pandey et al., Ijpsr, 2011; vol. 2(10): 2746-2749 .  Yassin el-said hamza and mona hassan aburahma design and in vitro evaluation of novel sustained-release double-layer tablets of lornoxicam: utility of cyclodextrin and xanthan gum combination. Aaps pharmscitech. 2009 dec