Diclofenac Sodium By Direct Compression Method

Published Date: 02 Nov 2017

Main author: Mehul B Ranpariya1, Chintan H Trivedi1, Sarita P Ratanpara1, Ramesh B Parmar1.

S.J.Thakkar pharmacy college Rajkot

Postbox No. 1508 , Avadh Road,

Near N.R.I. Bunglows,

kalawad Road,

Opp. Drive In Cinema,

Rajkot 360005, Gujarat, India.

Correspondence address: "Mehul"

Block No. 94

Kailash kewlum,

Opp. Pradhyuman green city

Kalawad road, Rajkot 360005.

E-mail: [email protected]

Abstract:

Fast disintegrating tablets are now-a-days prominence novel drug delivery because of the faster action. By adding different super disintegrating in different concentration achievement of fast disintegrating is achieved. Diclofenac is a traditional nonsterodial anti-inflammatory agent. It is nonselective cyclooxygenase inhibitor. It inhibits prostaglandin synthesis. And its sodium salt increases its solubility and reduces its side effects. As widely useful in rheumatic arthritis as well as osteoarthritis as a pain relief and wound healing. Here different 9 batches with different disintegrating agent concentration are shown among them croscarmelose (4%) and sodium starch glycolate (3%) showing best result among them.

Key words: Fast disintegrating, Diclofenac sodium, Croscarmelose sodium, Sodium starch glycolate, Quicker action.

INTRODUCTION:

Conventional tablet and capsules require higher disintegrating time and time require to reach the minimum effective concentration is higher which may not be beneficial for all cases, but now a-days newer dosage form fast disintegrating formulation are widely used to overcome this problem. This can be achieved through by formulation changes like by using super disintegrating or combination. And also some time many patients find it difficult to swallow tablets and hard gelatin capsules and thus do not comply with prescription, which results in high incidence of noncompliance and ineffective therapy.

Fast disintegrating tablets are known as fast dissolving/fast disintegrating/mouth dissolving, rapid-dissolve, and rapid melts, porous tablets, these are tablets that disintegrate within 3min. to form a suspension in a small amount of water. (1- 4)

When this tablet placed in mouth, rapidly dispersed or dissolved and can be swallowed in form of liquid. Recently fast dissolving formulation is popular as NDDS because they are easy to administer and lead to better patient compliance. 5

A solid dosage form that dissolve or disintegrates rapidly in oral cavity, resulting in solution or suspension without the need of water is the saliva will serve to rapidly dissolve the tablet & super disintegrate will rapidly disintegrate the tablet & aid in the dissolution of tablet. The mechanism by which tablet is broken down into smaller particles & then produces a homogeneous suspension or solution is based on Capillary action, and High swellabilty of disintegrates.

A wide range of drugs like cardiovascular, analgesics, antibiotics and narcotics are candidates for this dosage form. The technologies used in the manufacture of Fast dissolving tablets include tablet molding6 Freeze –drying or lyophilization7, direct compression, Spray drying8, Sublimation 9, and Mass extrusion.

Now a day diclofenac sodium fast disintegrating tablet formulated for the treatments of the osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Diclofenac inhibits PG synthesis and somewhat selective COX-2 inhibitors. Diclofenac block the pain sensitizing mechanism induced by the bradykinin, TNFα, interleukins (ILs). Therefore more effective against inflammation associated pain.10

MATERIALS AND METHODS

Materials

Diclofenac sodium was obtained as a gift sample from ACS chemicals Baroda. Croscarmellose and microcrystalline cellulose was obtained as a gift sample from Chemdyes Corporation Ahmadabad. Sodium saccharine was obtained as a gift sample from loba chemical Baroda. Sodium starch glycolate and magnesium stearate was obtained as a gift sample from suvidhinath laboratory Baroda. All other ingredient was of analytical grade.

Methods:

Sr.no

Ingredients(mg/tablet)

F1

F2

F3

F4

F5

F6

F7

F8

F9

1

Diclofenac

50

50

50

50

50

50

50

50

50

2

Croscarmelose sodium

3

4

5

-

-

-

3

4

5

3

Sodium starch glycolate

-

-

-

3

4

5

4

3

5

4

MCC

q.s

q.s

q.s

q.s

q.s

q.s

q.s

q.s

q.s

5

Sodium saccharine

3

3

3

3

3

3

3

3

3

6

Magnesium stearate

3

3

3

3

3

3

3

3

3

Table 1: Composition of various batch of diclofenac tablet.

PROCEDURE:

Weight all the material accurately by using digital weight balance (Model CP- 224 S). Passed all the materials through 80# sieve. Now mix all the material by graduated method in the mortar. After mixing press the tablet by using rotary tablet compression machine.

EVALUATION:

Tablet hardness11

The hardness of the tablets was determined by diametral compression using a dial type hardness tester (Model no 1101, Shivani Scientific Ind). A tablet hardness of about 4-5 kg is considered adequate for mechanical stability. Determinations were made in triplicate.

Tablet thickness12

Tablet thickness can be measured using a simple procedure. 5 tablets were taken and their thickness was measured using Varnier calipers. The thickness was measured by placing tablet between two arms of the Varnier calipers.

Tablet friability11

The friability of the tablets was measured in a Roche friabilator (Camp-bell Electronics, Mumbai). Tablets of a known weight (W0) or a sample of 20 tablets are dedusted in a drum for a fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated from the loss in weight as given in equation as below. The weight loss should not be more than 1 %. Determination was made in triplicate.

Uniformity of weight12

The weights were determined to within ±1mg by using Sartorious balance (Model CP- 224 S). Weight control is based on a sample of 20 tablets. Determinations were made in triplicate. The mean SD values were calculated.

In-vitro disintegration Time13

The test was carried out on 6 tablets using phosphate buffer pH 6.8 at 37ºC ± 2ºC was placed in a Petridis of 10 cm diameter. The table was then taken carefully positioned in the center of Petridis and the time required for the tablet to completely disintegrate into fine particles was noted.

Drug content14

For the drug content ten tablets were randomly selected from each formulation and pulverized to a fine powder. Now powdered tablet transfer to the 100ml volumetric flask and add distilled water to make 100ml. if require make appropriate dilution, and take absorbance in UV spectrometer at 276nm.

In-vitro dissolution study15

The release rate drug from fast dissolving tablets was determined using United State Pharmacopoeia (USP) XXIV dissolution testing apparatus II (paddle method). The dissolution test was performed using 900 ml of 0.1 N HCl (PH=1.2), at 37± 0.50C and 50 rpm. A sample (10 ml) of the solution was withdrawn from the dissolution apparatus at 2, 4, 6, 8, and 10min. The samples were replaced with fresh dissolution medium of same quantity. The samples were filtered through a 0.45 µ membrane filter. Absorbance of these solutions was measured at 285 nm using a Shimadzu UV-1601 UV/Vis double beam spectrophotometer. Cumulative percentage of drug release was calculated using an equation obtained from a standard curve.

Wetting time16

Five circular tissue paper were placed in a Petri dish of 10 cm diameter. 10 ml water containing 0.5% eosin, a water soluble dye, was added. The dye solution was used to identify complete wetting of the tablet surface. A tablet was carefully placed on the surface of the tissue paper in the Petridis at 25 0C. The time required for water to reach the upper surface of the tablet and to completely wet them was noted as the wetting time. These measurements were carried out in replicate of six.

CALIBRATION CURVE OF DICLOFENAC SODIUM

Accurately weight 100 of diclofenac sodium and dissolved in 100 ml phosphate buffer pH 6.8. By appropriate dilution to prepare 10, 20, 30 and 40µg/ml solution. Now measure UV absorbance at 276nm. Plot the calibration curve using Microsoft excel.

Fig.1: Standard curve of diclofenac sodium.

RESULT AND DISCUSSION:

Total nine formulations were prepared and evaluated. In all the formulation weight variation was within 1.93%, Hardness was within0.29%,Friability 0.25% all the formulation passed %friability limit, uniformity of drug content was more than 95.87% in the all formulations. Wetting time was determined all the formulations. Wetting time is more than 30sec. Disintegratation time is an important criterion for optimization of formulation. F1, F5 and F8 batches having lower disintegration time than other batches, among these F8 batch having optimum concentration of disintegrating agents concentration, these having a 7.33sec, disintegrating time.

Formulation code

Avg weight(mg)

±SD(n=3)

Hardness

(Kg/cm2)

±SD(n=3)

Wetting time

±SD(n=3)

Friability

±SD(n=3)

Disintegrating

Time(sec)

±SD(n=3)

Content uniformity.

F1

100.36±0.57

2.92±0.05

45.33±0.57

0.62±0.13

10.00±1.00

99.98

F2

99.36±0.58

2.54±0.20

54.66±0.57

0.57±0.12

12.66±1.52

95.96

F3

98.66±1.52

2.66±0.10

30.66±1.15

0.74±0.25

14.66±0.57

99.97

F4

99.14±0.83

2.15±0.06

60.33±0.57

0.65±0.02

12.66±0.57

97.26

F5

98.95±1.47

2.98±0.00

39.66±0.57

0.7±0.11

10.00±1.73

100.58

F6

100.89±1.01

2.56±0.29

42.66±1.52

0.86±0.13

11.66±0.52

98.09

F7

99.65±0.58

3.79±0.23

47.00±1.73

0.065±0.03

15.66±1.52

99.47

F8

99.77±1.93

2.74±0.13

34.23±1.52

0.45±0.02

7.33±0.57

96.57

F9

99.63±0.57

2.75±0.07

45.66±2.08

0.46±0.01

17.00±2.00

95.87

Table 2: Evaluation of prepared batches of diclofenac sodium tablets.

In vitro release studies

In vitro release of fast disintegrating tablets is similar to the conventional tablet. All prepared batches release more than 85.00% of the drug within 10min in vitro disintegration time considering wetting time, in vitro dissolution test, %friability and cumulative % drug released, formulation F8 was considered to be optimized.

Conclusion:

In this experiment prepared nine batches of different concentration of disintegrating agent from this F8 batch having better result so consider optimized formula as a F8 formulation.