carvedilol fdt
TRANSCRIPT
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DEVELOPMENT AND CHARACTERIZATION OF
CARVEDILOL FAST DISSOLVING TABLETS UTILIZINGCYCLODEXTRIN COMPLEXES
BY
PADMA, IV B.PHARMACY
UNDER THE GUIDANCE OF
BABU, M.PHARMACY, (Ph.D)
Institute of Pharmaceutical Sciences
, Guntur (D.t) - 522601
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OBJECTIVES
To obviate the demerit of pill swallowing difficulty in caseof geriatrics, fast dissolving tablets are preferred.
Present study aimed at developing the fast dissolvingtablets for a poorly soluble drug with low bioavailabilitydue to its first pass effect.
Development of FDT based on a effective drug-cyclodextrincomplex system.
Concept of fast dissolving tablets may overcome the firstpass metabolism.
Solubility enhancement obtained by complexation withcyclodextrins.
Increasing solubility may substantially contribute theenhancement of absorption consequently bioavailability.
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PLAN OF WORK
Literature review
Selection of drug and polymers
Procurement of materials
Preformulation studies
Preparation and characterization of drug-cyclodextrin complexes using different
concentrations of F-CD and HP- F-CD.
y Phase solubility study
y IR spectroscopy
y In vitro dissolution study
Optimization of type and ratio of cyclodextrin
Formulation and evaluation of carvedilol FDT
y Hardness
y Friability
y Disintegration
y Wetting time
y In vitro dissolution study
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MATERIALS
Carvedilol
F-cyclodextrin ( F-CD)
Hydroxypropyl- F-cyclodextrin (HP- F-CD)
Dichloromethane
Methanol
Mannitol Sodium starch glycolate
Crosspovidone
Crosscarmellose sodium
Magnessium stearate Talc
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EXPERIMENTA L METHODOLOGY
CA LIBRATION CURVE FOR CARVEDILOL IN 0.1 N HCL
A UV spectrophotometric method based on the measurement of absorbance at
242 nm in 0.1N HCl, was used in the present study for the estimation of
carvedilol.
0.1020
0.2013
0.4130
0.6167
0.8097
0.9887
y = 0.0993x + 0.0087
R² = 0.9992
0.0000
0.2000
0.4000
0.6000
0.8000
1.0000
0 2 4 6 8 10
A b s o r b a n c e
Concentration (µg/ml)
Figure 3.1.1: Calibration Curve of Carvedilol in 0.1 N HCl
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Phase solubility studies
Excess amount of carvedilol added to water containing CD
or HPCD (2-12 mM) were shaken at room temperature (25 ±
0.5°C) for 72 hours on a rotary shaker. After 48 hours of shaking to
achieve equilibrium, 2ml aliquots were withdrawn were filtered
using 0.45µ nylon disc filter. Samples were diluted suitably and
measure at 242 nm against blanks.
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0 2 4 6 8 10 12 C o n c e n t r a t i o n o f C a r v e d i l o l ( m M )
Concentration of Cyclodextrins (mM)
CD
HPCD
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CHARACTERIZATION OF DRUG-CYCLODEXTRIN COMPLEXES
IR Spectroscopy of pure drug and complex were
taken.
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I N VITRO DISSOLUTION STUD Y
77.2
83.588.6
99.47 99.82 99.14
0
20
40
60
80
100
C-CD (1:1) C-CD (1:2) C-CD (1:3) C-HPCD(1:1)
C-HPCD(1:2)
C-HPCD(1:3)
% D
r u g R e l e a s e d
DISSO 2000, Lab India 8-Station Dissolution Test Apparatus with a
paddle stirrer. powder containing drug: cyclodextrin complexes
equivalent to 6.25 mg of carvedilol was studied in 900 ml of 0.1N HCl
as dissolution medium at a speed of 50 rpm and a temperature of
37±0.59
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PREPARATION OF CARVEDILOL FDT UTILIZING DRUG:CYCLODEXTRIN
COMPLEX SYSTEMS
Procedure:
y Required quantities of drug and excients were
weighed accurately and passed through sieve #40 and
were compressed in to tablet by direct compression
technique. Formulae given below
Ingredients CFDT 1 CFDT 2 CFDT 3 CFDT 4 CFDT 5 CFDT 6 CFDT 7 CFDT 8 CFDT 9
C-HPCD(1:1) 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25
Sodium starch
glycolate 7 8 9 - - - - - -
Crospovidone - - - 7 8 9 - - -
Croscarmellosesodium - - - - - - 7 8 9
Mannitol 82.75 81.75 80.75 82.75 81.75 80.75 82.75 81.75 80.75
Magnessium stearate 2 2 2 2 2 2 2 2 2
Talc 2 2 2 2 2 2 2 2 2
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EVALUATION OF VARIOUS PARAMETERS OF FDT
ParameterCFDT 1 CFDT 2 CFDT 3 CFDT 4 CFDT 5 CFDT 6 CFDT 7 CFDT 8 CFDT 9
Hardness
(kg/cm
3.5 4 4 3.5 4 4 4 4 4
Friability (%) 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
Disintegration
(min)
6.4 5.7 5 5.4 2.7 2.9 3 5.1 4.4
Wetting time
(min)
3.4 4.5 4.7 5.9 2.3 3 3 5.6 4
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I N VITRO DISSOLUTION PROFILES OF CARVEDILOL FAST
DISSOLVING TABLETS
0
20
40
60
80
100
120
OFDT
1
OFDT
2
OFDT
3
OFDT
4
OFDT
5
OFDT
6
OFDT
7
OFDT
8
OFDT
9
% C
a r v e d i l o l R e l e
a s e d
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RESULTS & DISCUSSION
Solid state of inclusion complexes were characterized by phase solubility studies and
were confirmed by FTIR analysis.
The drug content is uniform and dissolution enhancement efficacy is in the order of
HP- F-CD> F-CD.
Inclusion complexes of carvedilol with HP- F-CD (1:1) were found by dissolution
studies to be superior due to its greater hydrophilicity and higher wetting ability.
Fast dissolving tablets prepared employing optimized concentration of cyclodextrin
complexes of carvedilol with HP- F-CD (1:1) with different ratios of
superdisintegrants.
In-vitro dissolution study shows the tablet formulation CFDT 5 containing drug: HP-
F-CD in the ratio of 1:1 binary system with 8% cross povidone as super disintegrent
showed excellent dissolution profile 99.81% in 45 minutes when compared to other
formulations as well as marketed formulation.
The wetting time and disintegration time of these tablets is 2.3 and 2.7 minutes
respectively, the DE (30%) value is 3.17 and T50 (min) value is only 22minutes.
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CONCLUSIONS
Carvedilol fast dissolving tablet was developed and optimized,
CFDT 5 containing C-HPCD (1:1) employing 8% of crospovidone
showed better dissolution rate i.e 99.81% in 45 min when
compared to other formulations.
Wetting and disintegration times are in the order of
crospovidone<croscarmellose sodium<sodium starch glycolate.
Results of in vitro dissolution study are in agreement with the
disintegration values observed.
FDT containing co-precipitated drug with HPCD satisfied with
all the requirements for rapid dissolving , allowing more than
85% drug dissolved within 30 min.
Enhancement of dissolution rate may result in the increase of its
bioavailability with the possibility of reducing drug dose and side
effects.
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REFERENCES
1. Dong-han won et al. Improved physicochemical characteristics of
carvedilol solid dispersion particles by super critical anti-solventprecipitation process international journal of pharmaceutics 2005; 30(1):
199-208.
2. Dario leonardi et al. Development of predisolone: poly ethylene glycol
6000 fast release tablets from solid dispersions: solid-state
characterization, dissolution behaviour, and formulation parameters Aaps pharm sci tech. 2007; 8(4): 108.
3. Omaima A. sammour et al. Formulation and optimization of mouth
dissolve tablets containing carvedilol solid dispersion Aaps pharm sci
tech 2006; 7(2): 55.