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Naimish et al. / Pharma Science Monitor 8(3), Jul-Sep 2017, 225-242

Pharma Science Monitor 8(3), Jul-Sep 2017

STUDIES ON FILM COATED PULSATILE RELEASE FORMULATION OF

DIACEREIN

Naimish A. Sarkhejiya1*, Praful D. Bharadia2

1Senior Research Fellow, Emcure Pharmaceuticals Ltd., Adalaj, Gandhinagar-382421, Gujarat, India.2Professor, L. M. College of Pharmacy, Navrangpura, Ahmedabad-380009, Gujarat, India.

ABSTRACTThe objective of this study was to design and evaluate film coated pulsatile release formulationof Diacerein (use as a model drug) according to circadian rhythm. Cores containing Diacereindrug were prepared by direct compression method using croscarmellose sodium as a superdisintegrant. Core tablets were coated sequentially with pH dependent polymer of Eudragit S100and Eudragit L100. Coating solution was prepared by Eudragit S100 and Eudragit L100 aspolymers and Triethylcitrate as a plasticizer. A 23 full factorial design was used for optimizationof formulation. In this design, amount of croscarmellose sodium (% w/w, in core tablet), ratio ofEudragit S100 to Eudragit L100 and % weight gain of coating were evaluated to find Lag timeand In-vitro drug release of pulsatile drug delivery system. Compatibility of drugs with polymerswas assured by FTIR study.KEYWORDS: Pulsatile formulation, Diacerein, film coated tablets, Eudragit S100 and EudragitL100.

INTRODUCTION

Chronopharmaceutics, the drug delivery based on circadian rhythm is recently gaining much

attention worldwide. Various diseases like asthma, hypertension, and arthritis show circadian

variation, that demands time scheduled drug release for effective drug action. [1-3] To follow this

principle, one must have to design the dosage form so that it can be given at the convenient time,

e.g. bed time for the above mentioned diseases with the drug release in the morning. For this, a

pulsatile release profile, where the drug is released completely after a defined lag time, is

advantageous. A pulsatile drug delivery that can be administered at bed time but releases drug in

early morning would be a promising chronotherapeutics system. The majority of drugs are

preferentially absorbed from the small intestine. [4-7] Hence, drug release at site of better

absorption can improve therapeutic efficacy of drug. This is of more concern for drug delivery

that is meant for pulse drug release after a lag period of 6-8h following oral administration of

dosage form.

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Arthritis patients have a problem related to pain and inflammation in joint during morning time.

It’s mainly due to the diurnal variations in the levels of circulating proinflammatory cytokines,

tumor necrosis factor-α and/or interleukin-6. So, this study deals with formulation of pulsatile

dosage form which will be released drug at right time, right place, and in right amounts, holds

good promises of benefit to the patients. [8-10]

Diacerein, a purified anthraquinone derivative, has rhein (1,8-dihydroxy-3-

carboxyanthraquinone) as its active metabolite, and was first discovered in plants with anti-

inflammatory and analgesic activities. [11] Its wide range of biological activities have been

applied and discussed for several decades. However, the beneficial effect of diacerein has been

associated mainly with joint-derived tissues/cells (i.e., chondrocyte, synovial fibroblast,

subchondral osteoblast etc.) for osteoarthritis treatment. [12-15] Meta-analysis reports have found

diacerein to be significantly superior to placebo and comparable to nonsteroidal anti-

inflammatory drugs (NSAIDs) but with better tolerability and safety profiles. [16] To date, there

are no reports describing the therapeutic effects of Diacerein for periodontal diseases. Two

mechanisms of action have been validated: In-vitro inhibition of interleukin-1 (IL-1) synthesis,

the main cytokine involved in cartilage destruction, and activity on the synthesis of

proteoglycans, and hyaluronic acid, the principal component of cartilage. [17]

The goal of present research work in drug delivery is to develop a formulation that meets

therapeutic need relating to particular pathological conditions. Both variations in disease state

and plasma drug concentration need to be taken in consideration in developing a meaningful

drug delivery system.

MATERIALS AND METHODS

MATERIALS

Diacerein was gifted by Ami Life sciences. Croscarmellose sodium and microcrystalline

cellulose (Avicel PH 112) were gifted from FMC biopolymers, Mumbai, India. Mannitol SD 200

was gifted from ROQUETTE, Ahmedabad, India. Povidone K30 gifted from BASF, Mumbai,

India. Magnesium stearate was gifted from Peter Greven, Mumbai, India. Talc was gifted from

IMERYS, Mumbai, India. Triethyl citrate was gifted from MERK, Mumbai, India. Aerosil 200,

Eudragit S100 and Eudragit L100 were gifted from Evonik, Mumbai, India.

METHODS

Formulation of film coated pulsatile tablets

A 23 full factorial design was used in the present study for optimization of formulation. It is

suitable for investigating the quadratic response surfaces and for constructing a second-order



polynomial model, thus enabling optimization of the pulsatile drug delivery system. In this

design, three factors were evaluated, each at two levels with three center points and experimental

trials were performed at all eleven possible combinations. The effect of three independent

variables,

1. X1= Croscarmellose sodium

2. X2= Ratio of Eudragit S100:Eudragit L100

3. X3= % Weight gain of coating

were studied on the Lag time and In-vitro drug release of pulsatile drug delivery system. These

three independent variables were varied at two different levels as describe in Table 1. Hand book

of pharmaceutical excipients was suggested that 2-5% concentration of croscarmellose sodium

used as a disintegrating agent. So 3 mg and 7.5 mg range of croscarmellose sodium were taken

as a variable. % wt gain and ratio of polymer range were taken from previously trial based.

Preliminary studies provided a setting of the levels for each independent variable. Each of factor

and levels was transformed in such a way that the high level of each factor was (+1) and low

level was (-1).

Table 1: Transformed values for high and low levels

Variables Variable level

Independent Variable -1 1

Cross Carmellose Na (mg) 3 7.5

Eudragit S100 : Eudragit L100 80:20 90:10

% Wt Gain 10 14

Dependent variable

Lag time

T90 % drug release



Table 2: Formulation of Different Batches for 23 Full Factorial Designs

For Core tablets

Batch

No

Real Value Transformed Value

Croscarmellose

sodium (mg)

Croscarmellose

sodium (mg)

C1 3 -1

C2 5.25 0

C3 7.5 1

For Coating of tablets

Batch

No

Real Value Transformed Value

Core

tablet

batch No

Eudragit S100 :

Eudragit L100

% Wt

Gain

Core

tablet

batch No

Eudragit S100 :

Eudragit L100

%

Wt

Gain

D1 C1 80:20 10 -1 -1 -1

D2 C3 80:20 10 1 -1 -1

D3 C1 90:10 10 -1 1 -1

D4 C3 90:10 10 1 1 -1

D5 C1 80:20 14 -1 -1 1

D6 C3 80:20 14 1 -1 1

D7 C1 90:10 14 -1 1 1

D8 C3 90:10 14 1 1 1

D9 C2 85:15 12 0 0 0

D10 C2 85:15 12 0 0 0

D11 C2 85:15 12 0 0 0



Table 3: Composition of Batches According to 23 Full Factorial Designs

Ingredients C1 C2 C3Core Tablet (quantity in mg/Tablet)

Diacerein 50.00 50.00 50.00Croscarmellosesodium

3.00 5.25 7.50

Mannitol SD 200 50.00 50.00 50.00Povidone K30 4.50 4.50 4.50MCC (Avicel Ph112)

40.50 38.25 36.00

Aerosil 200 1.00 1.00 1.00Mg. Stearate 1.00 1.00 1.00Core Tablet Weight 150.00 150.00 150.00

Ingredients D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11Core TabletBatch No

C1 C3 C1 C3 C1 C3 C1 C3 C2 C2 C2

Coating of Tablet (quantity in mg/Tablet)Core TabletWeight

150.00

150.00

150.00

150.00

150.00

150.00

150.00

150.00

150.00

150.00

150.00

Eudragit S10010.4

810.4

811.7

911.7

914.6

714.6

716.5

016.5

013.3

513.3

513.3

5Eudragit L100 2.62 2.62 1.31 1.31 3.67 3.67 1.83 1.83 2.36 2.36 2.36Triethylcitrate 0.65 0.65 0.65 0.65 0.92 0.92 0.92 0.92 0.79 0.79 0.79Talc 1.31 1.31 1.31 1.31 1.83 1.83 1.83 1.83 1.57 1.57 1.57

Total Weight165.06

165.06

165.06

165.06

171.08

171.08

171.08

171.08

168.07

168.07

168.07

% Coating 10 10 10 10 14 14 14 14 12 12 12

Preparation of Core tablets

The Core tablets were prepared according to the composition given in table by direct

compression. [18- 20] By varying the concentration of microcrystalline cellulose (Avicel pH 112)

and Croscarmellose sodium, eleven different formulations were prepared. The core tablets were

prepared by direct compression. The tablet ingredients were passed through 40 # sieve, mixed

with each other according to the geometric dilution method & blended for 10 minutes in a

mortar. The Magnesium stearate was passed through 60 # sieve, mixed with above mixture &

blended for 5 minutes in a mortar. Now, this blend was subjected to Preformulation study &

compression. The powder blend was compressed using rotary tablet press.

Preparation of coating solution

The coating solution was prepared by dissolving Eudragit S100 and Eudragit L100 in mixture of

acetone and isopropyl alcohol (50:50) (8% w/w solution) using overhead stirrer and was stirred



until clear solution obtained. Add Triethylcitrate in the solution and stir it for 30 minutes. Add

talc in this solution and stir it for 10 minutes. Solution was prepared based on supplier technical

notes. This solution was then passed through sieve 60 # to remove un-dissolved solids.

Coating of core tablets

Table 4: Process parameters for the coating of core tablets in factorial formulation [19]

Process Parameter Condition

Nozzle Diameter 1.0 mm

Preaheating Temperature 40°-45°C

Preaheating Time 15 min

Inlet Temperture 30°-40°C

Bed Temperature 25°-30°C

Exhaust Temperature 25°-30°C

Gun to Bed Distance 2 to3 Inch

Spray Rate 6 to 10 gm/min

Curing Temperature 50°-60°C

Curing Time 2 hr

The core tablets were coated using Neocota coating machine. Core tablets were coated with a

Eudragit S100 and Eudragit L100 solution in mixture of acetone and isopropyl alcohol, using

triethylcitrate as a plasticizer. Dummy tablets were used in coating to maintain coating pan load.

The polymer solution was sprayed using spray gun onto the core tablets till the desired weight

gain. At each stage the coated tablets were further dried in the coating pan for 2 hr at 50°-60°C.

Percent weight gain was calculated by following equation

% Weight gain=Wt – W0

W0× 100

Where Wt = Weight of tablet after coating;

Wo = Initial weight of tablet.

Check point batch

The values of independent variables selected and composition of checkpoint batch was shown in

Table-5 and Table-6 respectively.



Table 5: Independent Variables in Checkpoint Batch

Trial No

Real Value

Croscarmellose Na

(mg)

Eudragit S100 :

Eudragit L100

% Wt

Gain

D12 6 85:15 12

Composition of checkpoint batch

Table 6: Composition of checkpoint batch

Ingredients D12

Core tablet (quantity in mg/Tablet)

Diacerein 50.00

Croscarmellose sodium 3.00

Mannitol SD 200 50.00

Povidone K30 4.50

MCC (Avicel Ph 112) 40.50

Aerosil 200 1.00

Mg. Stearate 1.00

Core Tablet Weight 150.00

Coating of Tablet (quantity in mg/Tablet)

Eudragit S100 13.35

Eudragit L100 2.36

Triethylcitrate 0.79

Talc 1.57

Total Weight 168.07

% Coating 12

Check point batch was prepared similar to the Factorial batches and evaluated for Core tablet and

coated tablet.

EVALUATION OF FORMULATION [22 - 25]

Evaluation of powder blend:

Powder blend of different Batches were evaluated for Physical properties. Factorial formulations

were evaluated for the powder blend property like Bulk density, Tapped density, Carr’s index,

Hausner’s ratio and Angle of repose.



Evaluation of core tablets:

The core tablets were evaluated for physical parameters such as weight variation, hardness,

friability, disintegration time and Drug content.

Evaluation of pulsatile tablets:

The Pulsatile release tablets (PRTs) were evaluated for lag time and In-vitro drug release study.

Rupture test (Lag time determination) [26]

The lag time of the tablets is defined as the time required for the outer coat to rupture. It was

determined visually using USP type II dissolution apparatus at 50 rpm. Media for the first 2 hr

was 900 ml of 0.1 N HCl (pH 1.2), then 2 hr was 4.5 acetate buffer and continued in phosphate

buffer pH 6.8 for the next 10 hr or as required.

In-vitro drug release study

The prepared coated tablets were subjected to In-vitro drug release sequentially in three different

suitable dissolution media to assess their ability to provide the desired lag time before drug

release. USP type-II dissolution apparatus was used. The dissolution medium for the first 2 hr

was 900 ml of 0.1 N HCl (pH 1.2) then 2 hr was 4.5 acetate buffer and continued in phosphate

buffer pH 6.8 for the next 10 hr or as required. The temperature of dissolution medium was

maintained at 37 ± 0.5 °C and the paddle was rotated at 50 rpm. An aliquot of 5 ml was

withdrawn at predetermined time intervals and replaced with an equal volume of the fresh

dissolution medium to maintain sink conditions. The samples were filtered through a 0.45 µm

syringe filter and analyzed at 340 nm [22], for the percentage drug release using an UV-Visible

spectrophotometer.

Drug Excipients Compatibility Studies:

The FT-IR spectra of the physical mixture of drugs–polymer were recorded to check interaction

between drugs and polymers. FT IR Spectrum of pure drugs and optimized formulation were

taken for checking compatibility study. The drugs and optimized formulation were previously

ground and mixed thoroughly with potassium bromide, an infrared transparent matrix, at 1:5

(Sample: KBr) ratio, respectively. The KBr discs were prepared by compressing the powders at a

pressure of 5 tons for 5 min in a hydraulic press. Scans were obtained at a resolution of 4 cm−1,

from 4,000 to 600 cm−1.

RESULTS AND DISCUSSION

Evaluation of Powder blend

Powder blend of different Batches were evaluated for Physical properties. Factorial formulations

were evaluated for the powder blend property like Bulk density, Tapped density, Carr’s index,



Hausner’s ratio and Angle of repose. The Carr’s index was found to be in range of 13.32 to 15.47

which was considered as good flow property. Angle of repose less than 30° indicates good flow

property of the powder blend. The bulk density of all the formulation was in the range of 0.482

to 0.497. Hausner’s ratio of all formulation was below 1.5 indicating good compression

characteristics.

Evaluation of Core tablets

The core tablets were evaluated for physical parameters such as weight variation, hardness,

friability, disintegration time and Drug content. According to the results of post-compression

parameters (tablets), tablets were obtained in the range with uniform thickness and acceptable

weight variations limit as per Pharmacopoeia specifications i.e. less than 7.5% for tablets of 150

mg of weight. The results are shown in Table-7. Hardness was found in the range for all the

factorial batches and friability for the same was found to be less than 1% indicating sufficient

mechanical integrity and strength of the prepared tablets.

Table 7: Evaluation parameters for core tablets of Factorial formulation

Batch C1 C2 C3

Hardness (Kp) * 6.88 ± 1.07 6.72 ± 0.81 6.45 ± 0.50

Diameter (mm) * 7.03 ± 0.011 7.03 ± 0.008 7.02 ± 0.005

Thickness (mm) * 4.06 ± 0.070 4.07 ± 0.029 4.09 ± 0.010

Uniformity of weight

(mg)** 151.33 ± 2.20 150.33 ± 2.79 149.54 ± 2.73

% Friability# 0.21 ± 0.06 0.26 ± 0.12 0.20 ± 0.08

Disintegration time

(min)*# 6.04 ± 0.43 3.03 ± 0.39 2.53 ± 0.71

Drug content (%)*# 99.56 ± 2.38 99.96 ± 1.58 100.62 ± 2.06

Water Content (By

KF) (%)*# 0.81 ± 0.18 0.80 ± 0.22 0.76 ± 0.23*Values are mean ± SD, (n=10), **Values are mean ± SD, (n=20),

#Values are mean ± SD, (n=3), *#Values are mean ± SD, (n=6)

Evaluation of pulsatile tablets

The Pulsatile release tablets (PRTs) were evaluated for Lag time and In-vitro drug release

study. Tablets of all the batches had smooth surface with attractive appearance. Lag time and In-



vitro drug release were significantly affected by concentration of croscarmellose sodium, ratio of

polymer (EudragitS100: Eudragit L100) and weight gain of coating. Lag time of tablets is

shown in Figure 1, which indicate that higher concentration of croscarmellose sodium decrease

lag time.

Figure 1: Lag time of tablets from formulation D1 to D11

In-vitro drug releases profile of tablets are shown in Figure 2 to 4. Eudragit S100 and Eudragit

L100 concentration and % weight gain of coating assist to hold drug release for certain period of

time due to its pH dependent solubility of Eudragit. Formulation D1 and D2 having a less

Eudragit S100 concentration, exhibit less lag time and fast drug release. While in the case of D3

to D8, increased Eudragit S100 concentration, which hold drug release according to its

concentration present in formulation.

Figure 2: In- vitro drug release of Diacerein from formulation D1 to D4

012345678

D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11

Lag

tim

e (h

r)

Batch No.

020406080100120

0 1 2 3 4 5 6 7 8 9 10

% D

rug

Rele

ase

Time (hr)

D1D2





Figure 5 and Figure 6 indicate that increased concentration of croscarmellose sodium which

decreased lag time and helps bursting effect for drug release. In case of ratio of Eudragit,

increased Eudragit S100 concentration which increased lag time and increased Eudragit L100

concentration which decreased lag time. Eudragit having a pH dependent solubility which

significantly affected on lag time. Eudragit L100 soluble in pH 5 and above. Eudragit S100

soluble in pH 7 and above. Combination of polymer (EudragitS100: Eudragit L100) were

required for achieved a lag time of 6 hr.

020406080100120

0 1 2 3 4 5 6 7 8 9 10

% D

rug

Rele

ase

Time (hr)

D5D6D7D8

020406080100120

0 1 2 3 4 5 6 7 8 9 10

% D

rug

Rele

ase

Time (hr)

D9D10D11



Significant factors for Lag time

As per ANOVA results, the Model F-value of 6.69 implies the model is significant. There is only

a 4.35% chance that an F-value this large could occur due to noise. Values of "Prob > F" less

than 0.05 indicate model terms are significant.

The "Lack of Fit F-value" of 0.01 implies the Lack of Fit is not significant relative to the pure

error. There is a 92.30% chance that a "Lack of Fit F-value" this large could occur due to noise.

Non-significant lack of fit is good.

Final Equation in Terms of Coded Factors:

Lag Time = 5.87 - 0.059 × A + 0.62 × B + 0.71 × C - 0.016 × AB - 0.031 × AC - 0.18 × AC

Final Equation in Terms of Actual Factors:

Lag Time = - 27.76807 + 0.18000 × croscarmellose sodium + 0.34233 × Eudragit S100: Eudragit

L 100 + 1.88771 × % Weight Gain - 1.44444E-003 × croscarmellose sodium ×

Eudragit S100: Eudragit L100 - 6.94444E-003 × croscarmellose sodium × %

Weight Gain - 0.017625 × Eudragit S100: Eudragit L100 × % Weight Gain

Significant factors for T90% drug release

As per ANOVA results, the Model F-value of 6.22 implies the model is significant. There is only

a 4.92% chance that an F-value this large could occur due to noise. Values of "Prob > F" less

than 0.05 indicate model terms are significant.

The "Lack of Fit F-value" of 16.53 implies the Lack of Fit is not significant relative to the pure

error. There is a 5.70% chance that a "Lack of Fit F-value" this large could occur due to noise.

Non-significant lack of fit is good.

Final Equation in Terms of Coded Factors:

Lag Time = 6.63 - 0.18 × A + 0.39 × B + 0.60 × C + 3.750E-003 × AB + 6.250E-003 × AC -

0.14 × BC

Final Equation in Terms of Actual Factors:

Lag Time = - 17.42723 - 0.12444 × croscarmellose sodium + 0.24650 × Eudragit S100: Eudragit

L 100 + 1.49396 × % Weight Gain + 3.33333E-004 × croscarmellose sodium ×

Eudragit S100: Eudragit L100 + 1.38889E-003 × croscarmellose sodium × %

Weight Gain - 0.014125 × Eudragit S100: Eudragit L100 × % Weight Gain



Figure 5: Contour plot and response surface plot of Y1 factor (Lag time)

Figure 6: Contour plot and response surface plot of Y2 factor (T90% Drug Release)

Design-Expert® SoftwareFactor Coding: ActualLag Time (hr)

Design Points7.28

4.51

X1 = A: croscarmellose NaX2 = B: Eudragit S100 : Eudragit L 100

Actual FactorC: % Weight Gain = 12.00

3.00 3.90 4.80 5.70 6.60 7.50

80.00

82.00

84.00

86.00

88.00

90.00Lag Time (hr)

A: croscarmellose Na (mg)

B:

Eu

dra

git

S1

00

: E

ud

rag

it L

10

0 (

Ra

tio

)

5.4

5.6

5.8

6

6.2

6.4

3

Design-Expert® SoftwareFactor Coding: ActualLag Time (hr)

Design points below predicted value7.28

4.51



80.0082.00

84.0086.00

88.0090.00

3.00 3.90

4.80 5.70

6.60 7.50

4.5

5

5.5

6

6.5

7

7.5

La

g T

ime

(h

r)

A: croscarmellose Na (mg)B: Eudragit S100 : Eudragit L 100 (Ratio)

Design-Expert® SoftwareFactor Coding: ActualT90% Drug Release (%)

Design Points7.73

5.47



3.00 3.90 4.80 5.70 6.60 7.50

80.00

82.00

84.00

86.00

88.00

90.00T90% Drug Release (%)


B:

Eu

dra

git

S1

00

: E

ud

rag

it L

10

0 (

Ra

tio

)

6.2

6.4

6.6

6.8

7

3

Design-Expert® SoftwareFactor Coding: ActualT90% Drug Release (%)

Design points below predicted value7.73

5.47



80.0082.00

84.0086.00

88.0090.00

3.00 3.90

4.80 5.70

6.60 7.50

5

5.5

6

6.5

7

7.5

8

T9

0%

Dru

g R

ele

ase

(%

)

A: croscarmellose Na (mg)B: Eudragit S100 : Eudragit L 100 (Ratio)



Figure 7: Overlap Contour plot

Evaluation of check point batch D12:

In-vitro dissolution study

Dissolution study of Formulation D12 was carried out in 0.1N HCl, 4.5 acetate buffer and

phosphate buffer pH6.8 and observes the effect of pH on drug release.

Figure 8: In- vitro drug release of Diacerein from formulation D12

From the Results of Dissolution Profile of Check Point Batch D12, it was concluded that there is

no significant difference in Experimental Lag time than that of Predictable one. Data of

Dissolution of batch D12 at different pH of dissolution media reveals that pH had not significant

effect on the lag time. Batch D12 release drug after lag time of 6.21 ± 0.06 hours, which is near

Design-Expert® SoftwareFactor Coding: ActualOverlay Plot

Lag TimeT90% Drug Release

Design Points



3.00 4.13 5.25 6.38 7.50

80.00

82.50

85.00

87.50

90.00Overlay Plot


B: Eu

dragit

S100

: Eud

ragit L

100 (

Ratio

)

Lag Time: 5.3

Lag Time: 6.3T90% Drug Release: 7

3

020406080100120

0 1 2 3 4 5 6 7 8 9 10

% D

rug

Rele

ase

Time (hr)

D12

Lag time: 5.84878T90% release 6.58873X1 6.00X2 85.00



to the said hypothesis of the study, 6 hours. Thus, batch D12 was the Optimized Batch of the

present study.

FTIR spectroscopy:

Figure 9: FTIR spectroscopy pure drugs and physical mixtures

Infrared spectra of drugs and polymers were used to study the compatibility between

them. No change in peak shows that there were no interaction between drugs and

polymers. The IR spectrum of the pure drug (Diacerein) and optimized form given in

figure.

The FTIR spectrum of drugs shows characteristic bands at 1768.78 cm-1 of carbonyl

group of ester, COOH (Carboxyl groups) stretching at 3313.71 cm-1 and 1620 cm-1 is

aromatic ring peak.

The FT-IR spectra of the physical mixture of drugs-polymer were recorded to check

interaction between drugs and polymers. The characteristic peak due to pure Diacerein

has appeared in the spectra without any markable change in the position. It indicates that

there were no chemical interaction between Diacerein and polymers.

The results of physical mixtures of drugs and various excipients revealed no considerable

changes in the IR peaks of drugs thereby indicating the absence of any interaction.

CONCLUSION

Consistent lag time, immediate release of the active pharmaceutical ingredient (API) and the

requirements for developing the chronotherapeutics was achieved with the developed

formulation. Diacerein was successfully formulated as a modified pulsatile drug deliver after




present study.

FTIR spectroscopy:





figure.



aromatic ring peak.







CONCLUSION







present study.

FTIR spectroscopy:





figure.



aromatic ring peak.







CONCLUSION






predetermine lag time of 5.5 hrs. Croscarmellose sodium is ideal excipient as super disintegrant

and swelling agent while Eudragit S100 and Eudragit L100 is ideal polymer showing predefinate

lag time. Thus this approach of pulsatile/programmable release where in tablet of Diacerein is

taken at bed time, releasing drug in the morning hours when the symptoms are more prevalent

can prove to be a revolution in the treatment of various inflammatory disorders like rheumatoid

arthritis, osteoarthritis and spondylitis.

ACKNOWLEDGEMENT

We acknowledge and thank the Emcure Pharmaceuticals Ltd., Gandhinagar for providing

necessary excipients, infrastructure, constant support and enthusiasm to carry this work.

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