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 enhancement of absorption consequently bioavailability. the

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.

1.0000 y = 0.0993x + 0.0087 R = 0.9992 0.6167

Absorbance

0.9887
0.8097

0.8000

0.6000 0.4130

0.4000 0.2013 0.2000 0.1020

0.0000

Concentration (g/ml)

10

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 0.5C) for 72 hours on a rotary shaker. After 48 hours of shaking to

achieve equilibrium, 2ml aliquots were withdrawn were filtered

using 0.45 nylon disc filter. Samples were diluted suitably and measure at 242 nm against blanks.
0.07

Concentration of Carvedilol (mM)

0.06 0.05 0.04 0.03 CD HPCD

0.02 0.01 0 0 2 4 6 8 10 12

Concentration of Cyclodextrins (mM)

CHARACTERIZATION OF DRUG-CYCLODEXTRIN COMPLEXES

IR Spectroscopy of pure drug and complex were taken.

IN VITRO DISSOLUTION STUDY

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 370.59
100 99.47 99.82 99.14

88.6
83.5 80 77.2

% Drug Released

60

40

20

0 C-CD (1:1) C-CD (1:2) C-CD (1:3) C-HPCD (1:1) C-HPCD (1:2) C-HPCD (1:3)

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 C-HPCD(1:1) Sodium starch glycolate Crospovidone Croscarmellose sodium Mannitol Magnessium stearate Talc CFDT 1 6.25 7 82.75 2 2 CFDT 2 6.25 8 81.75 2 2 CFDT 3 6.25 9 80.75 2 2 CFDT 4 6.25 7 82.75 2 2 CFDT 5 6.25 8 81.75 2 2 CFDT 6 6.25 9 80.75 2 2 CFDT 7 6.25 7 82.75 2 2 CFDT 8 6.25 8 81.75 2 2 CFDT 9 6.25 9 80.75 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

3.5

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

5.4

2.7

2.9

5.1

4.4

Wetting time (min)

3.4

4.5

4.7

5.9

2.3

5.6

IN VITRO DISSOLUTION PROFILES OF CARVEDILOL FAST

DISSOLVING TABLETS
120 100
% Carvedilol Released

80 60 40 20 0 OFDT OFDT OFDT OFDT OFDT OFDT OFDT OFDT OFDT 1 2 3 4 5 6 7 8 9

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-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-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. Omaima A. sammour et al. Formulation and optimization of mouth dissolve tablets containing carvedilol solid dispersion Aaps pharm sci tech 2006; 7(2): 55.

3.

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