CARVEDILOL FDT

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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



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.



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



MATERIALS

Carvedilol

F-cyclodextrin ( F-CD)

Hydroxypropyl- F-cyclodextrin (HP- F-CD)

Dichloromethane

Methanol

Mannitol Sodium starch glycolate

Crosspovidone

Crosscarmellose sodium

Magnessium stearate Talc



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



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achieve equilibrium, 2ml aliquots were withdrawn were filtered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





CHARACTERIZATION OF DRUG-CYCLODEXTRIN COMPLEXES

IR Spectroscopy of pure drug and complex were

taken.



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



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



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



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



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.



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.



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.



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CARVEDILOL FDT