20110424_kiran et al IJAPR.pdf - international journal of advances ...

B. Kiran Kumar et al. / International Journal of Advances in Pharmaceutical Research 

IJAPR 

Available Online through 

www.ijapronline.org 

Research Article 

ISSN: 2230 – 7583 

FORMULATION DEVELOPMENT AND EVALUATION OF FAST DISSOLVING TABLET OF 

CARVEDILOL USING SUPER DISINTEGRANTS AND SOLID DISPERSION TECHNIQUE 

B. Kiran Kumar *1 , S.Suresh Kumar 1 , M.Lakshman Chandu 1 , K.Mallikarjuna Rao 2 , 

S.V.Krishna prasanth 3 . 

1 Vels University, Velam Nagar, P.V.Vaithiyalingam Road, Pallavaram, Chennai – 600 117. 

2 Ratnam Institute of Pharmacy, Pidathapolur – 524346, Nellore, A.P, India. 

3 Vels College of Pharmacy, M.G.R University, Velam Nagar, P.V.Vaithiyalingam Road, Pallavaram, 

Chennai – 600 117. 

Received on 04- 01- 2011 Revised on 27-01-2011 Accepted on 03-02-2011 

ABSTRACT 

Oral Disintegrating Tablet ODT is a solid dosage form containing medicinal substances which disintegrates 

rapidly, usually within a matter of seconds, when placed under the tongue. Therefore the present investigation is 

concerned with the development of Oral Disintegrant Tablet (ODT) of Carvedilol. In the present research work, the 

fast dissolving tablets were prepared using superdisintegrants like Ac-Di-sol, SSG and polymer is PEG by Solid 

Dispersion with dry granulation method. Those tablets were evaluated for weight variation, hardness, friability, taste 

masking, disintegration and In-Vitro drug release. Eight formulations of Carvedilol was prepared it was found that 

the post compressional parameters like hardness, friability, weight variation, disintegration time, in-vitro drug 

release studies and taste masking parameters was found to be better formulation F-8. 

Key Words: 

Carvedilol, Solid Dispersion, dry granulation, Disintegrants, ethyl cellulose, PEG, Ac-Di-sol, SSG. 

INTRODUCTION 

Numerous solid dispersion systems have 

been demonstrated in the pharmaceutical literature to 

improve the dissolution properties of poorly watersoluble 

drugs. Other methods, such as salt formation, 

complexation with cyclodextrins, solubilization of 

drugs in solvent(s), and particle size reduction have 

also been utilized to improve the dissolution 

properties of poorly water-soluble drugs; however, 

there are substantial limitations with each of these 

techniques 1,2,3 . 

Correspondence address 

B.Kiran kumar, 

M.Pharmacy, 

1 Vels University, 

Velam Nagar, 

P.V.Vaithiyalingam Road, 

Pallavaram, Chennai – 600 117, 

E-Mail: kirankumarboggarapu@gmail.com 

Mobile No: 9849070388. 

On the other hand, formulation of drugs as solid 

dispersions offers a variety of processing and 

excipient options that allow for flexibility when 

formulating oral delivery systems for poorly watersoluble 

drugs. With recent advances in molecular 

screening methods for identifying potential drug 

candidates, an increasing number of poorly watersoluble 

drugs are being identified as potential 

therapeutic agents. In fact, it has been estimated that 

40% of new chemical entities currently being 

discovered are poorly water-soluble 2 . Unfortunately, 

many of these potential drugs are abandoned in the 

early stages of development due to solubility 

concerns. It is therefore becoming increasingly more 

important that methods for overcoming solubility 

limitations be identified and applied commercially 

such that the potential therapeutic benefits of these 

active molecules can be realized 4, 5, 6 . 

Tablet is the most popular among all dosage 

forms existing today because of its convenience of 

self administration, compactness and easy 

IJAPR / Feb 2011/ Vol. 2 / Issue. 2/ 45 - 51 45


manufacturing; however hand tremors, dysphasia in 

case of geriatric patients, the underdeveloped 

muscular and nervous systems in young individuals 

and h case of uncooperative patients, the problem of 

swallowing is common phenomenon which leads to 

poor patient compliance 7, 8 . 

To overcome these drawbacks, mouth 

dissolving tablets (MDT) or orally disintegrating 

tablets; (ODT) has emerged as alternative oral dosage 

forms. These are novel types; of tablets that 

disintegrate/dissolve/ disperse in saliva within few 

seconds'. According to European Pharmacopoeia, the 

ODT should disperse/disintegrate in less than three 

minutes. The basic approach used in development of 

MDT is the use of superdisintegrants like Cross 

linked carboxymelhylcellulose (Croscarmeliose), 

Sodium starch glycolate (Primogel, Explotab). 

Polyvinylpyrrolidone (Polyplasdone) etc. which 

provide instantaneous disintegration of tablet after 

putting on tongue, thereby releasing the drug in 

saliva. The bioavailability of some drugs may be 

increased due to absorption of drugs in oral cavity 

and also due to pregastric absorption of saliva 

containing dispersed drugs that pass down into the 

stomach. Moreover, the amount of drug that is 

subject to first pass metabolism is reduced as 

compared to standard tablets 9, 10 . 

The rate of absorption and the extent of 

bioavailability for such insoluble hydrophobic drug 

are controlled by the rate of dissolution. Hence, an 

attempt has been made to increase the dissolution of 

such poorly water soluble drugs into solid dispersions 

to increase their effectiveness and simultaneously 

reduce their doses and hence the toxic effect. Solid 

dispersions traditionally have been used as an 

effective method to improve the dissolution 

properties and bioavailability of poorly water soluble 

drugs. Many substances can be employed as carriers 

to prepare solid dispersions. Among the popular 

carriers used in the formation of solid dispersion are 

polyethylene glycol and 2HP-β-cyclodextrin. Both 

polymers are often employed as a vehicle due to its 

low toxicity, low melting point, rapid solidification 

rate, high aqueous solubility. These and other 

properties make them a very suitable vehicle for 

formulations into dosage forms. The main objective 

of work is to improve the dissolution properties and 

bioavailability of carvedilol by solid dispersion 11 . 

MATERIALS AND METHODS 

COMPATABILITY STUDIES FOR DRUG AND 

POLYMERS 

Fourier Transform Infra-Red Spectroscopy 

(FTIR) 

The Fourier transform infra-red (FTIR) 

analysis was conducted for the structure 

characterization. FTIR of pure drug, polymer, and 

selected formulation were recorded. Samples were 

taken in a KBr pellet using ABB BOMEN MB 104 

SERIES FTIR instrument. Approximately 5 mg of 

spectroscopic grade KBr and samples were scanned 

in the IR range from 500 to 1500 cm -1 with a 

resolution of 4 cm -1 . 

Powder X-ray diffraction 

XRD patterns were recorded using Philips PW 1729 

X-ray generator (Computer 1710). Powder X-ray 

diffraction patterns were traced for carvedilol, PEG 

4000 and solid dispersion F 8 . The position and 

intensities of diffraction peaks were considered for 

the identification and comparison of crystallinity of 

the drug or carrier. 

PREPARATION OF CARVEDILOL SOLID 

12, 13 

DISPERSION TABLET 

The required quantities of each formulation 

(composition mentioned in table No: 01) were 

weighed and transferred to separate container. All the 

ingredients passed through the sieve no 40 

individually. After that all the ingredients were mixed 

by using the polythene bag. The mixed powder 

content were compressed into tablet by using rotary 

punching machine. 

EVALUATION OF TABLETS 

14, 15 

Thickness and diameter 

The thickness and diameter of the tablets 

were found out using Vernier Caliper and the results 

were expressed in millimeter. A 5% may be 

allowed depending on the size of the tablet. 

Hardness test 16 

Tablets require a certain amount of strength 

or hardness and resistance to friability to withstand 

mechanical shocks of handling in manufacture, 

packing and shipping. The hardness of tablet was 

measured by Monsanto hardness tester. Ten tablets 

from the batch were used for hardness studies and 

results are expressed in Kg/cm 2 . 

Weight variation test 17 

Ten tablets were selected at random, 

individually weighed in a single pan electronic 

balance and the average weight was calculated. The 

uniformity of weight was determined according to I.P 

specification. As per I.P not more than two of 

individual weight would deviate from average weight 



by not more than 5% and none deviate by more than 

twice that percentage. 

Friability test 18 

It was performed in Roche Friabilator 

apparatus where the tablets were subjected to the 

combined effect of abrasion and shock by utilizing a 

plastic chamber that revolves at 25 rpm dropping the 

tablets at a distance of six inches with each 

revolution. Preweighed samples of 20 tablets were 

placed in the Friabilator, which is then operated for 

100 revolutions. The tablets are then dedusted and 

reweighed. Conventional compressed tablets that 

loose less than 0.5 to 1% of their weight are generally 

considered acceptable. 

Drug content analysis 19 

Carvedilol solid dispersion tablets were 

tested for their drug content. The tablet was finely 

powdered in a mortar and pestle. Tablet equivalent to 

10 mg of Carvedilol was accurately weighed and 

transferred to a 100 ml standard flask. To the drug 

powder, methanol was added and made up to the 

volume with distilled water. It was shaken thoroughly 

for 30 minutes to ensure complete solubility of the 

drug. 10ml of the resultant liquid was pipetted out in 

another standard flask and volume was made up to 

100ml with distilled water. The absorbance of the 

final solution was measured at 244 nm in a UV- 

Visible spectrophotometer (Shimadzu). The amount 

of drug and the percentage purity of each formulation 

were evaluated. 

In-vitro drug release 20 

Tablet dissolution was assessed using standard USP 

dissolution apparatus type II taking 900ml of 

dissolution medium, pH 6.8 for 25 min. The 

rotational speed of the paddle was set at 50 rpm at 37 

± 0.5º C. The 5 ml of aliquots was withdrawn at 

predetermined time interval for every 1 min for 25 

min by maintaining sink condition. The samples were 

analyzed for drug content using double beam UV 

spectrophotometer at 244nm. 

RESULTS AND DISCUSSION 

The aim of this work was to investigate the 

influence of PEG 4000 in solid dispersion on the 

physiochemical characteristics and dissolution rate of 

Carvedilol. In order to analyze the prepared 

products, selective physical determinations based on 

FTIR spectroscopy, XRD were used. The results 

revealed that the rate of dissolution could be 

enormously improved by making Carvedilol solid 

dispersion with PEG 4000. PEG 4000 was used 

extremely as carriers for dispersions due to their low 

melting point and their hydrophilic environment. So, 

it is used as carrier for the solid dispersion. 

In the present study, solid dispersion tablets 

of Carvedilol and PEG 4000 in 1:4 by using 

combination of two superdisintegrants were made. 

Based on the results out x 100 of all the formulations, the 

formulation f8 having the combination of 

superdisintegrants (Ac-Di-Sol, Sodium starch 

glycolate) in 2% concentration shown the best drug 

release at the end of the 5min in Sorenson buffer pH 

6.8. Hence it was concluded that f8 formulation was a 

desirable formulation. This ensures that solid 

dispersion technique have reduced the drug particle 

size and changes the micro environment of the drug 

particle, which increases the rate of dissolution and 

absorption and thus changes the biopharmaceutical 

properties of poorly water soluble drugs. 

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Table: 01, Composition Of Solid Dispersion Tablets 

Quantity in mg 

Ingredients F1 F2 F3 F4 F5 F6 F7 F8 

Carvedilol 12.5 12.5 12.5 12.5 _ _ _ _ 

Carvedilol+PEG _ _ _ _ 62.6 62.6 62.6 62.6 

4000 

Ac-Di-Sol 3.75 5 _ _ 1.25 1.25 2.5 2.5 

SSG _ _ 3.75 5 1.25 2.5 1.25 2.5 

Dextrose 18 18 18 18 _ _ _ _ 

Lactose 18 18 18 18 _ _ _ _ 

Sorbitol 25 25 25 25 18.75 18.75 18.75 18.75 

Mannitol 12.5 11.25 12.5 11.25 11.15 9.9 9.9 8.65 

MCC 25 25 25 25 25 25 25 25 

Talc 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 

Magnesium 

stearate 

2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 

Table 02, Precompression properties of formulations 

S.No 

Formulation 

Code 

Angle of 

repose(º) 

Bulk 

density(g/ml) 

Tapped 

density(g/ml) 

Compressibility 

index 

Hausner’s 

Ratio 

1 F1 25.25 0.439 0.457 3.938 1.025 

2 F2 28.45 0.431 0.449 4.008 1.018 

3 F3 25.12 0.449 0.476 5.672 1.068 

4 F4 26.10 0.451 0.491 8.146 1.166 

5 F5 23.91 0.368 0.395 6.835 1.103 

6 F6 27.46 0.456 0.493 7.505 1.157 

7 F7 27.01 0.367 0.392 6.377 1.098 

8 F8 25.92 0.447 0.473 5.496 1.058 



Table No: 03, Results for fast dissolving tablets of Carvedilol. 

S.No 

Formulatio 

Hardness(kg/ Friability Disintegr 

n Code Thickness(mm) cm2) (%) ation time 

1 F1 3.15 4.40 0.77 53 

2 F2 3.48 5.20 0.43 41 

3 F3 3.53 4.37 0.48 59 

4 F4 3.54 5.13 0.77 43 

5 F5 3.50 4.17 0.55 51 

6 F6 3.41 4.33 0.41 41 

7 F7 3.49 4.67 0.63 39 

8 F8 3.61 4.63 0.55 35 

S.No 

Table 04, Assay of formulations 

Weight of 

SD(mg) 

Weight of SD equivalent to 

12.5mg of Carvedilol 

Formulations 

% drug content 

1 F1 25 98.96 ± 0.12 26.3 

2 F2 37.5 98.12 ± 0.25 38.4 

3 F3 50 97.45 ± 0.36 51.2 

4 F4 62.5 99.86 ± 0.45 63.5 

5 F5 75 99.14 ± 0.78 76.3 

6 F6 87.5 97.45 ± 0.14 88.3 

7 F7 100 98.35 ± 0.74 101.3 

8 F8 112.5 99.63 ± 0.87 113.5 

TIME(min) 

Table 10: In-vitro drug release of formulations 

% CUMULATIVE DRUG RELEASE 

F1 F2 F3 F4 F5 F6 F7 F8 

5 45.3 60.5 43.5 50.5 65.24 68.46 70.79 72.2 

10 53.7 69.7 50.06 59.7 70.29 72.18 75.26 79.29 

15 65.8 74.9 59.5 65.9 77.88 78.53 79.78 82.62 

20 75.06 80.7 67.12 72.7 83.96 84.98 85.47 89.38 

25 85.78 90.06 77.78 83.63 92.06 94.56 96.7 99.64 



FOURIER TRANSFORM INFRARED 

SPECTROSCOPY 

X - RAY DIFFRACTION 

Figure 04, XRD diffractogram of Carvedilol, 

Figure01 : FTIR of Carvedilol 

Figure 05, XRD diffractogram of PEG 4000 

Figure 02, FTIR of PEG 4000 

Figure 03, FTIR of Carvedilol + PEG 4000 

Fig No: 06, Formulation XRD 



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