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DEVELOPMENT AND CHARACTERIZATION OF CARVEDILOL FAST DISSOLVING TABLETS UTILIZING
CYCLODEXTRIN COMPLEXES
BY
XXXXXX, IV B.PHARMACY
UNDER THE GUIDANCE OF
BABU, M.PHARMACY, (Ph.D)
Institute of Pharmaceutical Sciences, Guntur (D.t) - 522601
OBJECTIVES
To obviate the demerit of pill swallowing difficulty in case of geriatrics, fast dissolving tablets are preferred.
Present study aimed at developing the fast dissolving tablets for a poorly soluble drug with low bioavailability due to its first pass effect.
Development of FDT based on a effective drug-cyclodextrin complex system.
Concept of fast dissolving tablets may overcome the first pass metabolism.
Solubility enhancement obtained by complexation with cyclodextrins.
Increasing solubility may substantially contribute the enhancement of absorption consequently bioavailability.
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 -CD and HP--CD.
Phase solubility study
IR spectroscopy
In vitro dissolution study
Optimization of type and ratio of cyclodextrin
Formulation and evaluation of carvedilol FDT
Hardness
Friability
Disintegration
Wetting time
In vitro dissolution study
MATERIALS
Carvedilol -cyclodextrin (-CD) Hydroxypropyl- -cyclodextrin (HP--CD) Dichloromethane Methanol Mannitol Sodium starch glycolate Crosspovidone Crosscarmellose sodium Magnessium stearate Talc
EXPERIMENTAL METHODOLOGY
CALIBRATION 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 + 0.0087R² = 0.9992
0.0000
0.2000
0.4000
0.6000
0.8000
1.0000
0 2 4 6 8 10
Abs
orba
nce
Concentration (µg/ml)
Figure 3.1.1: Calibration Curve of Carvedilol in 0.1 N HCl
Phase solubility studies
Excess amount of carvedilol added to water containing
βCD or HPβCD (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achieve equilibrium, 2ml aliquots were withdrawn were filtered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 12Con
cent
ratio
n of
Car
vedi
lol (
mM
)
Concentration of Cyclodextrins (mM)
βCD
HPβCD
CHARACTERIZATION OF DRUG-CYCLODEXTRIN COMPLEXES
IR Spectroscopy of pure drug and complex were taken.
IN VITRO DISSOLUTION STUDY
C-βCD (1:1) C-βCD (1:2) C-βCD (1:3) C-HPβCD (1:1)
C-HPβCD (1:2)
C-HPβCD (1:3)
0
20
40
60
80
100
77.283.5
88.6
99.47 99.82 99.14
% D
rug
Rel
ease
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
PREPARATION OF CARVEDILOL FDT UTILIZING DRUG:CYCLODEXTRIN COMPLEX SYSTEMS
Procedure:
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-HPβCD(1:1) 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25Sodium starch glycolate 7 8 9 - - - - - -
Crospovidone - - - 7 8 9 - - -Croscarmellose sodium - - - - - - 7 8 9
Mannitol 82.75 81.75 80.75 82.75 81.75 80.75 82.75 81.75 80.75Magnessium stearate 2 2 2 2 2 2 2 2 2Talc 2 2 2 2 2 2 2 2 2
EVALUATION OF VARIOUS PARAMETERS OF FDT
Parameter CFDT 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
IN VITRO DISSOLUTION PROFILES OF CARVEDILOL FAST DISSOLVING TABLETS
0
20
40
60
80
100
120
OFDT1
OFDT2
OFDT3
OFDT4
OFDT5
OFDT6
OFDT7
OFDT8
OFDT9
% C
arve
dilo
l Rel
ease
d
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--CD> -CD.
Inclusion complexes of carvedilol with HP--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--CD (1:1) with different ratios of
superdisintegrants.
In-vitro dissolution study shows the tablet formulation CFDT 5 containing drug:
HP--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.
CONCLUSIONS Carvedilol fast dissolving tablet was developed and
optimized, CFDT 5 containing C-HPβCD (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 HPβCD 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.
REFERENCES
1. Dong-han won et al. Improved physicochemical characteristics of carvedilol solid dispersion particles by super critical anti-solvent precipitation 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.
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