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achieve equilibrium, 2ml aliquots were withdrawn were filtered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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