4: Analytical Profile of Aceclofenac - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/28939/15/15...Result and Discussion Department of Pharmaceutical Sciences, Bhagwant University,

Result and Discussion

Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 96

4: Analytical Profile of Aceclofenac:

4.1: Differential Scanning Calorimetry:

DSC provides information about the physical properties of the sample as crystalline or

amorphous nature and demonstrates a possible interaction between drug and polymers in

Formulations. According to the thermograms, aceclofenac presented a sharp endothermic

peak at 158.3ºC corresponding to the melting point of the drug in the crystalline form.

The DSC graphs are given in fig.4.1

Fig. 4.1 DSC spectrum of Aceclofenac 4.2 STANDARD CURVE OF ACECLOFENAC:

4.2.1Preparation of 0.1 N HCl:

85 ml of concentrated hydrochloric acid was diluted upto 1000 ml with distilled water. 10

ml of resulting solution was further diluted to 100 ml with distilled water.

4.2.2 Scanning of Aceclofenac in 0.1 N hydrochloric acid (HCl):

The solution containing 10 g/ml of Aceclofenac in 0.1 N HCl was prepared and scanned

over the wavelength range of 200 nm to 400 nm against 0.1 N HCl as a blank using

double beam UV spectrophotometer. The plot of absorbance v/s wavelength was

recorded using double beam UV spectrophotometer.



4.2.3 Preparation of standard curve in 0.1 N HCl:

An accurately weighed quantity of Aceclofenac (100mg) was dissolved in 100 ml of 0.1

N HCl to generate a stock solution having concentration of 1mg/ml. 2 ml of stock

solution was further diluted to 100 ml to produce standard solution having concentration

of 20g/ml. The standard solution was serially diluted with 0.1 N HCl to get working

standard solution having concentration of 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 g/ml. The

absorbance of the solutions was measured at 256 nm using double beam UV visible

spectrophotometer against 0.1 N HCl as a blank. The plot of absorbance v/s concentration

(g/ml) was plotted and data was subjected to linear regression analysis in Microsoft

Excel®.

4.2.4 Observation:

The standard calibration curve of drug in 0.1 N HCl is depicted as Fig.4.2 The data of

absorbance was shown in Table 4.1. The data had correlation coefficient of 0.999.

Table 4.1: Standard curve of Aceclofenac in 0.1 N HCl at 256.0 nm

Concentration (g/ml) Absorbance

0 0.000

2 0.121

4 0.242

6 0.355

8 0.468

10 0.585

12 0.699

14 0.815

16 0.930

18 1.057

20 1.169



Standard Curve of Accelofenac in 0.1N HCl

y = 0.0582x + 0.0035R2 = 0.9999

0

0.2

0.4

0.6

0.8

1

1.2

0 2 4 6 8 10 12 14 16 18 20

Concentration (mcg/ml)

Abs

orba

nce

Fig. 4.2 Standard Plot of Aceclofenac in 0.1 N HCl

The linear regression analysis for standard curve: The linear regression analysis was done on Absorbance data points. The results are as

follows:

For standard curve in 0.1N HCL

The slope = 0.0582

The intercept = 0.0035

The correlation coefficient = 0.9999

A straight-line equation (Y = mx + c) was generated to facilitate the calculation of

amount of drug. The equation is as follows.

Absorbance = 0.0582× Concentration + 0.0035



4.3: Determination of absorption maxima (max) for analysis

A solution of Aceclofenac (5µg/ml) in 0.1 N HCl, when scanned between 200nm to

400nm exhibits absorption maxima (λmax) at 256 nm, which is concordant with the

Clarke's Analysis of Drugs and Poisons shown in Fig. 4.3

-0.5

1.5

0

0.5

1

200 350250 300

Abs

Wavelength[nm]

Fig. 4.3 UV Spectrum of Aceclofenac in 0.1 N HCl.

4.4 Drug Excipients Interaction Study:159

While formulating gastro retentive tablet, it is imperative to give consideration to the

compatibility of drug and polymer used within the system. It is therefore necessary to

confirm that drug is not interacting with polymer under experimental conditions and shelf

life. The FTIR analysis is the most powerful technique for qualitative compound

identification. The main application of FTIR spectrophotometry is determination of the

identity of a compound by means of spectral comparison with that of an authentic sample

and verification of the presence of functional groups in an unknown molecule. The

samples were powdered and intimately mixed with dry powdered potassium bromide.

The powdered mixture was taken in a diffuse reflectance sampler and the spectra

recorded by scanning in the wavelength region of 2.5 to 25 in a FTIR

spectrophotometer.The IR spectrum of drug was compare with that of the physical

mixture to check for any possible drug-excipients interaction.

From the FTIR spectral interpretation the following result were obtained.



The FTIR of Aceclofenac show intense band at 1715.88cm-1, 1619.84cm-1 ,1456.27cm-1

and 1241.26cm-1 corresponding to the functional groups C=O, COOH, NH and OH

bending. The IR graphs were given in fig: 4.4-4.8

Table 4.2 Drug Polymer Compatibility Study Data

Mixtures Discoloration Liquefication Clump Formation

HPMCK4M - - -

CARBAPOL 934 P - - -

CARBAPOL 971 P - - -

Other (crosspovidone,sodium bicarbonate,all polymers and Drug)

- - -

+ Incompatibility; - compatibility

Table 4.3 Drug-Polymer interaction studies:

Mixture Principles peaks at Wave number

(cm-1)

Drug 1715.88, 1619.84,1456.27, 1241.26

Drug+ HPMC K4M 1716.19,1621.72, 1462.79, 1241.29

Drug+Carbopol 934P(C34) 1716.19, 1621.63, 1461.54,1242.70

Drug+Carbopol 971 P(C71) 1716.03, 1621.74,1461.57,1242.83

Drug+HPMC+Carbopol+Crosspovidone+Sodium

bicarbonate+PVP K-30

1715.78, 1621.85, 1458.34, 1240.80



Fig. 4.4 IR spectrum of Aceclofenac

Fig. 4.5 IR Spectra of mixture of Drug and HPMC K4M



Fig. 4.6 IR Spectra of mixture of Drug and Carbopol 934P

Fig. 4.7 IR Spectra of mixture of Drug and Carbopol 971P



Fig. 4.8 IR Spectra of mixture of Drug, HPMC, Crosspovidone, Sodium Bicarbonate

and PVP K-30

4.5 Characterization of floating drug delivery systems:

4.5.1 Evaluation of granules

The granules prepared in the formulation of floating tablets were evaluated for angle of

repose, bulk density, tapped density, porosity, Carr's index and Hausner ratio. The results

are presented in table 4.4

The angle of repose was below then 300 showed good to excellent flow properties of

powder. Lower the friction occurring within the mass and better flow rate. The angle of

repose was found to be 22.71 to 28.880. This indicates the good flow property of the

mixed blends.

The bulk density of mixed blend varied between 0.568 to 0.673 gm/cm3. The results

indicating good packaging capacity of tablets.

The tapped density was found in the range of 0.634 to 0.776 gm/cm3. By using these two

density data Hausners Ratio and compressibility index was calculated. If the bed of the

particles is more compressible then the powder will be less flowable and vice versa.

Material having value less than 20 % termed as free flow materials. The powder blends of

all the formulation had hausners ratio of 1.2 or less indicating the good flowability. The



compressibility index was found between 10.34 to 13.26. And the compressibility –

flowability correlation data indicated a fairly good flowability of the powder blend.

Table 4.4 Evaluation of Blends

Parameter Angle of Repose(θ)

Bulk Density (mg/ml)

Tapped Density (mg/ml)

Hauners Ratio

Compressibility Index (%) Formulation

F1 25.827±1.675 0.673±0.010 0.776±0.029 1.152±0.023 13.265±1.672 F2 26.406±1.203 0.589±0.023 0.666±0.031 1.131±0.025 11.607±1.262

F3 25.900±1.109 0.628±0.031 0.702±0.028 1.117±0.027 10.476±1.623

F4 28.885±1.576 0.661±0.028 0.758±0.039 1.149±0.031 13.065±1.213

F5 26.575±1.320 0.611±0.033 0.717±0.027 1.148±0.008 12.962±1.278

F6 25.706±0.923 0.634±0.007 0.634±0.018 1.130±0.023 11.538±1.291

F7 28.071±1.328 0.568±0.025 0.653±0.016 1.115±0.032 10.344±2.328 F8 27.348±1.134 0.584±0.027 0.640±0.026 1.118±0.039 10.619±1.259 F9 26.706±0.914 0.573±0.031 0.694±0.023 1.157±0.029 10.434±1.906 F10 26.565±0.973 0.603±0.008 0.660±0.013 1.150±0.011 13.636±2.018 F11 28.787±1.004 0.573±0.023 0.680±0.036 1.134±0.028 11.818±0.775 F12 28.298±1.281 0.667±0.032 0.715±0.031 1.29±0.031 11.447±1.243

F13 23.282±0.984 0.633±0.039 0.649±0.035 1.118±0.029 11.498±2.332

F14 24.231±1.042 0.574±0.027 0.717±0.014 1.126±0.039 12.447±1.259

F15 23.405±1.571 0.628±0.029 0.648±0.019 1.122±0.027 11.316±2.329

F16 24.065±0.963 0.574±0.009 0.718±0.009 1.134±0.029 12.212±1.837

F17 22.713±0.863 0.584±0.011 0.711±0.017 1.136±0.033 14.051±2.985 F18 25.706±0.929 0.627±0.034 0.714±0.029 1.112±0.031 12.220±1.916 F19 24.900±0.918 0.628±0.015 0.702±0.036 1.117±0.023 11.538±1.213 F20 25.706±1.112 0.634±0.17 0.709±0.028 1.139±0.028 12.264±1.105 F21 28.177±1.294 0.622±0.012 0.648±0.019 1.130±0.010 10.476±1.958



4.5.2 Characterization of floating tablets

The prepared floating tablets were evaluated for weight variation, hardness, friability,

drug content, floating characteristics, and in-vitro drug release and stability studies. The

results of the physicochemical characterization are shown in table 4.5

All the formulations are white in colour, odorless, flat in shape with smooth surface with

zero defects. The prepared tablets were elegant and lot – to – lot tablet uniformity, free

from any surface texture problems.

The average weight of the prepared tablet was found 329.4 to 340.2 mg. so it was

predicted that all the formulation exhibited uniform weight with low standard deviation

values within the acceptable variation as per IP.

From the experiment hardness was found between 3.5 to 4.5 kg/cm3. Which have

satisfactory strength to withstand the mechanical shocks.

The friability of all the formulation was found to be less than 1.0 %. This shows the

durability of the prepared tablets. The results shows resistance to loss of weight indicates

the tablet’s ability to withstand abrasion in handling, packaging and shipment

These all results shows the uniformity of playing and filling of die and punch of punching

machine and no any processing problem like capping, lamination, picking and sticking

were shown. The thickness of a tablet is determined by the diameter of the die, the

amount of fill permitted to enter the die, and the force or pressure applied during

compression. The uniform tablet thickness shows the uniform die filling and uniform

pressure to prepare tablet. The degree of pressure not only affects the thickness of the

tablet but also hardness of tablet. Hardness is perhaps the more important criterion since

it can affect disintegration and dissolution. Thus, for tablets of uniform thickness and

hardness, it is doubly important to control pressure. A tablet requires certain amount of

hardness to withstand the mechanical shocks in handling, packaging and at the time of

application.

The floating lag time and floating time is shown in table 4.6



Table 4.5 Physio-chemical Characterization of Floating Tablets

Parameter Thickness (mm)

Weight (mg)

Friability (%)

Hardness (kg/cm2)

Assay (%)

Formulation

F1 4.124±0.008 330.1±0.912 0.75±0.042 3.5±0.133 98.23

F2 4.278±0.018 332.2±0.230 0.49±0.039 3.5±0.095 99.11

F3 4.424±0.006 335.1±1.821 0.67±0.053 3.7±0.125 99.44

F4 4.672±0.005 337.6±1.342 0.76±0.055 3.6±0.113 99.17

F5 4.462±0.014 331.5±0.038 0.69±0.046 4.1±0.109 99.34

F6 5.198±0.067 334.7±0.564 0.72±0.073 3.8±0.165 99.20

F7 4.377±0.081 338.3±1.543 0.69±0.036 3.5±0.093 99.50

F8 4.367±0.011 336.8±1.453 0.57±0.054 4.2±0.152 99.40

F9 5.016±0.028 329.4±1.176 0.66±0.075 4.5±0.096 99.98

F10 4.987±0.033 340.2±2.123 0.68±0.047 3.9±0.136 99.99

F11 5.156±0.021 337.5±1.234 0.71±0.043 4.1±0.104 101.2

F12 5.282±0.015 336.3±1.986 0.59±0.038 3.6±0.138 99.79

F13 4.209±0.041 335.2±1.947 0.69±0.063 3.7±0.091 99.87

F14 4.267±0.034 330.9±2.432 0.74±0.085 3.9±0.124 101.1

F15 4.368±0.069 338.6±2.342 0.69±0.076 4.0±0.342 99.50

F16 4.398±0.081 331.5±1.985 0.74±0.062 3.7±0.113 101.23

F17 4.467±0.014 337.2±2.432 0.46±0.039 3.6±0.133 99.88

F18 4.492±0.024 339.5±2.675 0.63±0.058 3.7±0.142 97.19

F19 4.378±0.038 340.2±2.345 0.72±0.051 3.8±0.132 99.34

F20 4.362±0.061 334.8±2.985 0.69±0.047 3.9±0.564 99.12

F21 4.856±0.076 336.3±1.876 0.84±0.067 3.8±0.086 99.23



Table 4.6 Physical Properties of Floating Tablet of ACECLOFENAC

Parameter Density (g/cm3)

Floating Duration(hr)

Floating Lag time(sec)

Formulation

F1 0.838±0.059 12±0.6 35.3±3.6

F2 0.816±0.034 12±1.5 38.2±5.0

F3 0.812±0.024 20±1.7 25.6±3.4

F4 0.844±0.029 16±1.8 29.3±4.2

F5 0.936±0.181 20±1.3 33.8±3.4

F6 0.875±0.071 20±3.2 42.0±4.8

F7 0.893±0.097 12±1.0 27.8±3.2

F8 0.992±0.102 22±1.6 28.6±3.7

F9 0.910±0.036 16±1.7 30.5±3.6

F10 0.876±0.043 12±3.2 32.9±3.3

F11 0.987±0.086 24±1.8 1280±40.0

F12 0.780±0.099 24±0.6 -

F13 0.753±0.046 24±1.7 -

F14 0.686±0.087 24±1.8 -

F15 0.769±0.101 24±1.3 -

F16 0.651±0.090 24±0.5 -

F17 0.717±0.078 24±1.1 -

F18 0.798±0.156 24±1.5 -

F19 0.693±0.137 24±0.8 -

F20 0.737±0.112 24±0.6 -

F21 0.758±0.114 24±1.4 -



Table 4.7 Percentage Swelling of formulation with Time from FH1-FH10

Time (hr)

Percentage Swelling F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

0 0 0 0 0 0 0 0 0 0 0 1 20.44 27.98 39.44 18.79 22.48 40.23 23.67 36.23 41.56 44.98 2 35.22 38.87 51.98 32.48 45.65 55.78 36.65 53.03 57.87 61.94 3 43.89 56.43 65.18 45.65 54.89 62.26 53.87 68.81 71.98 78.36 4 49.54 91.83 99.10 54.89 71.22 102.19 87.98 94.67 104.76 115.47 8 57.63 99.53 120.58 71.44 102.72 155.12 97.56 101.87 128.98 140.47 12 83.24 110.54 145.59 102.34 114.57 158.67 103.87 128.56 137.68 148.74 16 95.94 120.34 170.48 117.72 115.99 160.68 116.45 144.67 145.98 155.76

20 113.44 138.93 209.41 128.40 125.78 175.72 118.51 152.17 153.87 168.85 24 114.42 140.95 210.45 128.43 131.72 193.48 120.53 155.96 155.98 170.87

Table 4.8 Percentage swelling of formulation with Time from F11-F21

Time (hr)

Percentage Swelling F11 F12 F13 F14 F15 F16 F17 F18 F19 F20 F21

0 0 0 0 0 0 0 0 0 0 0 0 1 26.09 22.76 25.79 24.96 20.69 18.96 24.76 35.96 34.67 24.67 23.65 2 35.53 33.76 37.46 29.63 27.49 31.63 36.98 53.37 51.38 33.87 30.87 3 53.89 48.98 52.97 39.37 36.70 42.37 51.86 79.78 77.79 48.96 49.75 4 70.87 69.45 68.94 53.23 48.49 56.23 70.76 92.38 89.56 62.65 63.84 8 90.09 88.67 86.90 66.76 63.29 70.76 88.39 128.87 116.38 82.76 82.47

12 98.67 97.75 96.95 74.56 70.59 78.56 95.18 138.31 130.65 90.53 88.95 16 124.76 122.45 120.76 85.48 82.86 89.48 118.46 142.65 142.36 114.76 120.76 20 138.76 134.65 133.49 91.41 85.80 93.89 126.86 148.67 149.73 134.76 126.87 24 152.76 150.87 149.56 96.39 91.65 100.39 146.76 149.76 150.65 140.38 138.65



Maximum Percentage Swelling of all the Formulation at Time 8 h

0

50

100

150

200

250

F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

F11

F12

F13

F14

F15

F16

F17

F18

F19

F20

F21

Formulations

Perc

enta

ge S

wel

ling

Fig. 4.9 Maximum Percentage swelling of all the Formulation at Time 8 h.



4.5.3 DRUG RELEASE KINETICS AND MECHANISM OF DRUG RELEASE

Table 4.9 Zero Order Dissolution Release Profile of Aceclofenac from F1-F5 Values are expressed as mean (S.D.), n=6

Time

(hr)

Cumulative Percent Drug Release F1 F2 F3 F4 F5

0 0 0 0 0 0

1 15.32±1.54 17.63±1.65 13.23±1.13 14.81±1.36 15.75±1.67

2 24.63±1.83 27.88±1.78 24.34±1.16 20.17±1.19 23.74±1.15

3 30.87±1.19 31.83±1.82 33.56±1.48 29.88±1.18 31.06±1.56

4 36.66±1.76 38.76±1.74 44.67±1.19 41.77±1.78 40.15±1.45

6 42.53±1.87 49.46±1.16 56.78±1.89 50.34±2.19 47.73±2.14

8 56.38±2.18 63.23±1.67 62.85±2.15 59.25±2.67 54.87±2.45

10 62.44±2.79 71.23±2.75 68.87±2.57 65.67±2.89 69.03±2.89

12 65.89±2.94 78.67±2.63 72.86±3.16 72.78±3.12 76.96±2.98

16 69.76±2.67 82.76±3.18 82.75±3.67 74.86±3.34 81.87±3.16

20 72.45±3.14 85.68±3.26 95.98±3.38 82.43±3.31 83.45±3.33

24 75.41±3.48 88.17±3.79 98.67±2.79 84.76±3.12 86.75±3.87

Zero Order Dissolution Release Profile of Aceclofenac from F1-F5

0

20

40

60

80

100

120

0 1 2 3 4 6 8 10 12 16 20 24

Time (hrs)

Cum

ulat

ive

Per

cent

Dru

g R

elea

se

F1F2F3F4F5

Figure 4.10 Zero Order Dissolution Release Profile of Aceclofenac from F1-F5



Table 4.10 Zero Order Dissolution Release Profile of Aceclofenac from F6-F10

Values are expressed as mean (S.D.), n=6

Time(hr)


0 0 0 0 0 0

1 8.16±1.12 10.29±1.34 13.02±1.13 14.78±1.56 12.56±1.13

2 18.02±1.13 21.69±1.67 21.86±1.56 22.12±1.45 20.98±1.56

3 26.14±1.16 32.06±1.87 30.98±1.45 30.08±1.23 28.73±1.89

4 30.09±1.47 42.65±1.78 46.06±1.56 39.88±1.87 36.87±1.78

6 36.23±1.78 51.29±1.98 54.73±1.87 46.37±1.89 44.23±1.79

8 43.34±1.89 58.87±2.68 62.34±2.54 54.78±2.34 52.34±2.12

10 54.69±1.98 68.98±3.76 72.08±2.87 67.36±2.98 64.82±2.34

12 57.09±2.13 75.67±3.45 78.09±2.89 74.76±2.67 72.56±2.78

16 58.87±2.78 79.95±3.14 82.73±3.63 78.98±3.12 76.87±2.78

20 61.85±2.98 82.23±3.87 86.83±3.98 83.08±3.16 79.08±2.87

24 64.87±2.98 91.35±2.58 93.75±3.87 84.45±2.79 80.56±3.78


0

20

40

60

80

100

0 1 2 3 4 6 8 10 12 16 20 24

Time(hrs)

Cu

mul

ativ

e Pe

rcen

t Dr

ug R

elea

se F6

F7F8F9F10

Figure 4.11 Zero Order Dissolution Release Profile of Aceclofenac from F6-F10




values are expressed as mean(S.D.), n=6

Time(hr) Cumulative Percent Drug Release F11 F12 F13 F14 F15

0 0 0 0 0 0

1 9.03±1.12 9.37±1.17 10.45±1.13 17.94±1.45 19.78±1.23

2 18.32±1.73 19.03±1.65 21.63±1.45 28.49±1.16 23.23±1.56

3 27.93±1.78 25.76±1.16 27.87±1.56 41.76±1.78 31.06±1.67

4 31.02±1.67 29.87±2.11 31.67±1.89 49.05±1.89 41.56±1.78

6 32.32±1.65 34.76±2.14 39.45±2.12 55.34±2.17 58.65±2.12

8 44.06±1.67 43.34±2.43 45.76±2.13 64.81±2.67 68.34±2.12

10 55.63±2.17 52.56±2.76 55.65±2.35 78.48±3.23 74.67±2.67

12 57.81±2.87 59.35±2.89 62.76±2.87 82.56±3.43 78.98±3.56

16 59.45±2.87 64.72±3.13 69.45±3.12 86.27±3.78 82.78±3.56

20 62.96±2.67 67.37±3.15 75.36±3.15 88.76±3.98 86.34±3.23

24 66.87±3.12 70.67±2.79 85. 43±3.78 90.56±3.17 88.56±3.65


0

20

40

60

80

100

0 1 2 3 4 6 8 10 12 16 20 24

Time(hr)

Cum

ulat

ive

Perc

ent D

rug

Rel

ease

F11F12F13F14F15

Fig.4.12 Zero Order Dissolution Release Profile of Aceclofenac from F11-F15




values are expressed as mean (S.D.), n=6

Time

(hr)

Cumulative Percent Drug Release

F16 F17 F18 F19 F20 F21

0 0 0 0 0 0 0

1 7.86±1.12 10.54±1.43 15.86±1.56 11.23±1.13 13.45±1.34 12.67±1.13

2 12.65±1.23 20.56±1.67 28.56±2.12 22.45±2.11 24.67±1.36 22.76±1.34

3 20.85±1.45 27.78±1.78 37.98±2.23 32.62±2.13 34.86±1.89 33.67±1.76

4 22.76±1.61 32.87±1.89 53.56±2.54 56.65±2.26 52.85±2.13 50.87±2.11

6 28.14±1.87 38.78±2.11 70.71±3.34 71.29±2.68 68.45±2.56 67.34±2.46

8 38.17±1.39 49.76±2.13 75.56±3.34 78.98±2.89 72.78±2.45 70.32±2.75

10 43.87±2.13 58.45±3.15 80.83±3.23 80.84±3.13 78.98±3.11 74.56±3.36

12 53.76±2.34 64.67±3.72 82.45±3.12 84.56±3.32 82.36±3.23 78.34±3.45

16 62.63±2.54 69.47±3.56 85.76±3.54 87.65±3.23 86.34±3.26 82.36±3.57

20 72.94±2.89 76.56±3.33 87.34±3.47 90.23±3.17 88.02±2.96 86.23±3.22

24 86.56±3.29 78.65±2.24 89.67±3.23 92.65±3.15 89.78±3.22 88.98±3.79


0

20

40

60

80

100

0 1 2 3 4 6 8 10 12 16 20 24

Time(hrs)

Cum

ulat

ive

Perc

ent D

rug

Rel

ease

F16F17F18F19F20F21

Fig.4.13 Zero Order Dissolution Release Profile of Aceclofenac from F16-F21



Table 4.13 First Order Dissolution Release of Aceclofenac from F1-F5

Time

(hr)

Log Cumulative Percent Drug Retain F1 F2 F3 F4 F5

0 2 2 2 2 2

1 1.927 1.915 1.938 1.930 1.925

2 1.865 1.858 1.878 1.902 1.882

3 1.839 1.833 1.822 1.845 1.838

4 1.801 1.787 1.742 1.765 1.777

6 1.759 1.703 1.635 1.696 1.718

8 1.639 1.565 1.569 1.610 1.654

10 1.574 1.458 1.493 1.535 1.490

12 1.532 1.328 1.433 1.434 1.362

16 1.480 1.236 1.236 1.400 1.258

20 1.440 1.155 0.604 1.244 1.218

24 1.390 1.072 0.123 1.182 1.122

First Order Dissolution Release Aceclofenac from F1-F5

0

0.5

1

1.5

2

2.5

0 1 2 3 4 6 8 10 12 16 20 24

Time (hr)

Log

Cum

ulat

ive

Perc

ent

Dru

g R

etai

n F1F2F3F4F5

Fig: 4.14 First Order Dissolution Release Aceclofenac from F1-F5



Table 4.14 First Order Dissolution Release Profile of Aceclofenac from F6-F10

Time(hr)


0 2 2 2 2 2

1 1.963 1.952 1.939 1.930 1.941

2 1.913 1.893 1.892 1.891 1.897

3 1.868 1.832 1.838 1.844 1.852

4 1.844 1.727 1.762 1.779 1.800

6 1.804 1.587 1.701 1.729 1.746

8 1.753 1.417 1.630 1.655 1.678

10 1.656 1.322 1.567 1.513 1.546

12 1.632 1.238 1.490 1.402 1.438

16 1.614 1.115 1.327 1.322 1.364

20 1.581 1.032 1.119 1.228 1.320

24 1.545 0.937 0.795 1.191 1.288

First Order Dissolution Release Profile of Aceclofenac from F6-F10

0

0.5

1

1.5

2

2.5

0 1 2 3 4 6 8 10 12 16 20 24

Time(hr)

Log

Cum

ulat

ive

Perc

ent D

rug

Ret

ain

F6F7F8F9F10





Time(hr)


0 2 2 2 2 2

1 1.958 1.957 1.952 1.914 1.904

2 1.912 1.908 1.894 1.854 1.885

3 1.857 1.870 1.858 1.765 1.838

4 1.838 1.845 1.834 1.707 1.766

6 1.830 1.814 1.782 1.649 1.616

8 1.747 1.753 1.734 1.546 1.500

10 1.647 1.676 1.646 1.332 1.403

12 1.625 1.609 1.571 1.241 1.322

16 1.607 1.547 1.485 1.137 1.236

20 1.568 1.513 1.391 1.050 1.135

24 1.520 1.467 1.163 0.974 1.058


0

0.5

1

1.5

2

2.5

0 1 2 3 4 6 8 10 12 16 20 24

Time(hr)

Log

Cum

ulat

ive

Perc

ent D

rug

Ret

ain

F11F12F13F14F15





Time

(hr)

Log Cumulative Percent Drug Retain

F16 F17 F18 F19 F20 F21

0 2 2 2 2 2 2

1 1.964 1.951 1.925 1.948 1.937 1.941

2 1.941 1.900 1.853 1.889 1.876 1.887

3 1.898 1.858 1.792 1.828 1.813 1.821

4 1.887 1.826 1.666 1.636 1.673 1.691

6 1.856 1.786 1.466 1.458 1.498 1.514

8 1.791 1.701 1.388 1.322 1.434 1.472

10 1.749 1.618 1.282 1.282 1.322 1.405

12 1.665 1.548 1.244 1.188 1.246 1.335

16 1.572 1.484 1.153 1.091 1.135 1.246

20 1.492 1.369 1.102 0.989 1.078 1.138

24 1.405 1.329 1.014 0.866 1.009 1.042


0

0.5

1

1.5

2

2.5

0 1 2 3 4 6 8 10 12 16 20 24

Time (hr)

Lo

g Cu

mul

ativ

e Pe

rcen

t Dru

g R

etai

n F16F17F18F19F20F21

Fig: 4.17 First Order Dissolution Release Profile of Aceclofenac from F16-F21



Table 4.17 Higuchi Model Representing Release Profile of Aceclofenac from F1- F5

SQRTof

Time (hr)


0 0 0 0 0 0

1.00 15.32±1.54 17.63±1.65 13.23±1.13 14.81±1.36 15.75±1.67

1.41 26.63±1.83 27.88±1.78 24.34±1.16 20.17±1.19 23.74±1.15

1.73 30.87±1.19 31.83±1.82 33.56±1.48 29.88±1.18 31.06±1.56

2.00 36.66±1.76 38.76±1.74 44.67±1.19 41.77±1.78 40.15±1.45

2.44 42.53±1.87 49.46±1.16 56.78±1.89 50.34±2.19 47.73±2.14

2.82 56.38±2.18 63.23±1.67 62.85±2.15 59.25±2.67 54.87±2.45

3.16 62.44±2.79 71.23±2.75 68.87±2.57 65.67±2.89 69.03±2.89

3.46 65.89±2.94 78.67±2.63 72.86±3.16 72.78±3.12 76.96±2.98

4.00 69.76±2.67 82.76±3.18 82.75±3.67 74.86±3.34 81.87±3.16

4.47 72.45±3.14 85.68±3.26 95.98±3.38 82.43±3.31 83.45±3.33

4.89 75.41±3.48 88.17±3.79 98.67±2.79 84.76±3.12 86.75±3.87

Higuchi Model Representing Release Profile of Aceclofenac from F1- F5

0

20

40

60

80

100

120

0 1 1.41 1.73 2 2.44 2.82 3.16 3.46 4 4.47 4.89

SQRTof Time (hr)

Cum

ulat

ive

Perc

ent D

rug

Rel

ease

F1F2F3F4F5

Fig: 4.18 Higuchi Model Representing Release Profile of Aceclofenac from F1- F5




SQRTof

Time(hr)


0 0 0 0 0 0

1.00 8.16±1.12 10.29±1.34 13.02±1.13 14.78±1.56 12.56±1.13

1.41 18.02±1.13 21.69±1.67 21.86±1.56 22.12±1.45 20.98±1.56

1.73 26.14±1.16 32.06±1.87 30.98±1.45 30.08±1.23 28.73±1.89

2.00 30.09±1.47 46.65±1.78 42.06±1.56 39.88±1.87 36.87±1.78

2.44 36.23±1.78 61.29±1.98 49.73±1.87 46.37±1.89 44.23±1.79

2.82 43.34±1.89 73.87±2.68 57.34±2.54 54.78±2.34 52.34±2.12

3.16 54.69±1.98 78.98±3.76 63.08±2.87 67.36±2.98 64.82±2.34

3.46 57.09±2.13 82.67±3.45 69.09±2.89 74.76±2.67 72.56±2.78

4.00 58.87±2.78 86.95±3.14 78.73±3.63 78.98±3.12 76.87±2.78

4.47 61.85±2.98 89.23±3.87 86.83±3.98 83.08±3.16 79.08±2.87

4.89 64.87±2.98 91.35±2.58 93.75±3.87 84.45±2.79 80.56±3.78


0

20

40

60

80

100

0 11.4

11.7

3 22.4

42.8

23.1

63.4

6 44.4

74.8

9

SQRTof Time(hr)

C

umul

ativ

e Pe

rcen

t Dru

g R

elea

se

F6F7F8F9F10





SQRTof

Time(hr)


0 0 0 0 0 0

1.00 9.03±1.12 9.37±1.17 10.45±1.13 17.94±1.45 19.78±1.23

1.41 18.32±1.73 19.03±1.65 21.63±1.45 28.49±1.16 23.23±1.56

1.73 27.93±1.78 25.76±1.16 27.87±1.56 41.76±1.78 31.06±1.67

2.00 31.02±1.67 29.87±2.11 31.67±1.89 49.05±1.89 41.56±1.78

2.44 32.32±1.65 34.76±2.14 39.45±2.12 55.34±2.17 58.65±2.12

2.82 44.06±1.67 43.34±2.43 45.76±2.13 64.81±2.67 68.34±2.12

3.16 55.63±2.17 52.56±2.76 55.65±2.35 78.48±3.23 74.67±2.67

3.46 57.81±2.87 59.35±2.89 62.76±2.87 82.56±3.43 78.98±3.56

4.00 59.45±2.87 64.72±3.13 69.45±3.12 86.27±3.78 82.78±3.56

4.47 62.96±2.67 67.37±3.15 75.36±3.15 88.76±3.98 86.34±3.23

4.89 66.87±3.12 70.67±2.79 85. 43±3.78 90.56±3.17 88.56±3.65


0

20

40

60

80

100

0 1

1.41

1.73 2

2.44

2.82

3.16

3.46 4

4.47

4.89

SQRTof Time(hr)

Cum

ulat

ive

Perc

ent D

rug

Rel

ease

F11F12F13F14F15Linear (F11)





SQRTof

Time

(hr)

Cumulative Percent Drug Release

F16 F17 F18 F19 F20 F21

0 0 0 0 0 0 0

1.00 7.86±1.12 10.54±1.43 15.86±1.56 11.23±1.13 13.45±1.34 12.67±1.13

1.41 12.65±1.23 20.56±1.67 28.56±2.12 22.45±2.11 24.67±1.36 22.76±1.34

1.73 20.85±1.45 27.78±1.78 37.98±2.23 32.62±2.13 34.86±1.89 33.67±1.76

2.00 22.76±1.61 32.87±1.89 53.56±2.54 56.65±2.26 52.85±2.13 50.87±2.11

2.44 28.14±1.87 38.78±2.11 70.71±3.34 71.29±2.68 68.45±2.56 67.34±2.46

2.82 38.17±1.39 49.76±2.13 75.56±3.34 78.98±2.89 72.78±2.45 70.32±2.75

3.16 43.87±2.13 58.45±3.15 80.83±3.23 80.84±3.13 78.98±3.11 74.56±3.36

3.46 53.76±2.34 64.67±3.72 82.45±3.12 84.56±3.32 82.36±3.23 78.34±3.45

4.00 62.63±2.54 69.47±3.56 85.76±3.54 87.65±3.23 86.34±3.26 82.36±3.57

4.47 68.94±2.89 76.56±3.33 87.34±3.47 90.23±3.17 88.02±2.96 86.23±3.22

4.89 74.56±3.29 78.65±2.24 89.67±3.23 92.65±3.15 89.78±3.22 88.98±3.79


0

20

40

60

80

100

0 11.4

11.7

3 22.4

42.8

23.1

63.4

6 44.4

74.8

9

SQRTof Time (hr)

Cum

ulat

ive

Perc

ent D

rug

Rel

ease

F16F17F18F19F20F21




Table 4.21 Korsmeyer Model Representing Release Profile of Aceclofenac from F1- F5

Log

Time (hr)

Log cumulative percentage of drug released F1 F2 F3 F4 F5

0 0 0 0 0 0

0 1.185 1.246 1.121 1.170 1.197

.3010 1.425 1.445 1.386 1.304 1.375

.4771 1.489 1.502 1.525 1.475 1.492

.6020 1.564 1.588 1.650 1.620 1.603

.7781 1.628 1.694 1.754 1.701 1.678

.9030 1.751 1.800 1.798 1.772 1.739

1 1.795 1.852 1.838 1.817 1.839

1.079 1.818 1.895 1.862 1.862 1.886

1.2041 1.843 1.917 1.917 1.874 1.913

1.3010 1.860 1.932 1.982 1.916 1.921

1.3802 1.877 1.945 1.994 1.928 1.938

Korsmeyer Model Representing Release Profile of Aceclofenac from F1- F5

0

0.5

1

1.5

2

2.5

0 00.3

01

0.477

10.6

02

0.778

10.9

03 11.0

79

1.204

11.3

01

1.380

2

Log Time (hr)

Log

cum

ulat

ive

perc

enta

ge

of d

rug

rele

ased F1

F2F3F4F5

Fig: 4.22 Korsmeyer Model Representing Release Profile of Aceclofenac from F1- F5




Log

Time (hr)


0 0 0 0 0 0

0 0.911 1.012 1.114 1.169 1.098

.3010 1.255 1.336 1.339 1.344 1.321

.4771 1.417 1.505 1.491 1.478 1.458

.6020 1.478 1.668 1.623 1.600 1.566

.7781 1.559 1.787 1.696 1.666 1.645

.9030 1.636 1.868 1.758 1.738 1.718

1 1.737 1.897 1.799 1.828 1.811

1.079 1.756 1.917 1.839 1.873 1.860

1.2041 1.769 1.939 1.896 1.897 1.885

1.3010 1.791 1.950 1.938 1.919 1.898

1.3802 1.812 1.960 1.971 1.926 1.906


0

0.5

1

1.5

2

2.5

0 00.3

01

0.477

10.6

02

0.778

10.9

03 11.0

79

1.204

11.3

01

1.380

2

Log Time (hr)

Log

cum

ulat

ive

perc

enta

ge

of d

rug

rele

ased F6

F7F8F9F10





Log

Time (hr)


0 0 0 0 0 0

0 0.955 0.971 1.019 1.253 1.296

.3010 1.262 1.279 1.335 1.454 1.366

.4771 1.446 1.410 1.445 1.620 1.492

.6020 1.491 1.475 1.500 1.690 1.618

.7781 1.509 1.541 1.596 1.743 1.768

.9030 1.644 1.636 1.660 1.811 1.834

1 1.745 1.720 1.745 1.894 1.873

1.079 1.762 1.773 1.797 1.916 1.897

1.2041 1.774 1.811 1.841 1.935 1.917

1.3010 1.799 1.828 1.877 1.948 1.936

1.3802 1.825 1.849 1.931 1.956 1.947


00.5

11.5

22.5

0 00.3

01

0.477

10.6

02

0.778

10.9

03 11.0

79

1.204

11.3

01

1.380

2

Log Time (hr)

Log

cum

ulat

ive

perc

enta

ge

of d

rug

rele

ased

F11F12F13F14F15





Log

Time (hr)

Log cumulative percentage of drug released

F16 F17 F18 F19 F20 F21

0 0 0 0 0 0 0

0 0.895 1.022 1.200 1.050 1.128 1.102

.3010 1.102 1.313 1.455 1.351 1.392 1.357

.4771 1.319 1.443 1.579 1.513 1.542 1.527

.6020 1.357 1.516 1.728 1.753 1.723 1.706

.7781 1.449 1.588 1.849 1.853 1.835 1.828

.9030 1.581 1.696 1.878 1.897 1.862 1.847

1 1.642 1.766 1.907 1.907 1.897 1.872

1.079 1.730 1.810 1.916 1.927 1.915 1.893

1.2041 1.796 1.841 1.933 1.942 1.936 1.915

1.3010 1.838 1.884 1.941 1.955 1.944 1.935

1.3802 1.872 1.895 1.952 1.966 1.953 1.949


00.5

11.5

22.5

0 00.3

01

0.477

10.6

02

0.778

10.9

03 11.0

79

1.204

11.3

01

1.380

2

Log Time (hr)

Log

cum

ulat

ive

perc

enta

ge

of d

rug

rele

ased

F16F17F18F19F20F21




4.5.4 SCANNING ELECTRON MICROSCOPY:

SEM has been used to determine particle size distribution, surface topography, texture

and to examine the morphology of fractured or sectioned surface. The SEM generally

used for generating three dimensional surface relief images derived from secondary

electrons.

Figure No. 26 (a): SEM of dry state Figure No. 26 (b) SEM after 4 hr swelling

Figure No. 26 (c) SEM after 8 hr swelling Figure No. 26(d) SEM after 12 hr swelling



Procedure for SEM Analysis:

The SEM analysis was conducted using scanning electron microscope for the optimized

formulation in the following states,

Dry tablet surface and

Tablets after swelling of 4, 8 and 12 hrs.

As with SEM high vaccum is required for image formation and samples must be

thoroughly desiccated before entering the vaccum chamber, therefore samples were

thoroughly dried after swelling for analysis. The dried samples were mounted on sample

holder using double sided adhesive carbon tape.

The SEM was operated at 15 KV. The condenser lens position was maintained at

a constant level. The photomicrographs were recorded at 500X. (Fig. 4.26).

4.5.5 Analysis of Drug Release Data: To analyze the mechanism of release and release rate kinetics of the dosage form, the

data obtained were fitted into Zero order, First order, Higuchi matrix, Peppas and Hixson

Crowell model. Based on the r-value, the best-fit model was selected.

The dissolution data obtained were plotted as:

(a) Cumulative percentage drug release vs. time as zero order,

(b) Log cumulative percentage drug retained vs. time as First order release kinetics,

(c) Cumulative percentage drug released vs. square root of time as Higuchi equation

and

(d) Log cumulative percentage drug released vs. Log time as per Korsemeyer and

Peppas equation.

The drug release data were explored for the type of release mechanism followed. The

best fit with the highest determination R2 coefficients was shown by both the Higuchi and

first order models followed by zero order which indicate the drug release via diffusion

mechanism.



Table 4.25 Kinetic of invitro release from floating tablet of Aceclofenac

Code Zero order (R2)

First order (R2)

Higuchi’ plot (R2)

Koresmeyer-peppas plot

n (R2) F1 0.9591 0.9887 0.9591 0.7898 0.5985

F2 0.9692 0.9767 0.9692 0.8013 0.6149

F3 0.9861 0.7909 0.9861 0.7577 0.6509

F4 0.9751 0.9871 0.9751 0.7523 0.6429

F5 0.9774 0.9718 0.9774 0.7681 0.6378

F6 0.9673 0.9865 0.9673 0.6541 0.6741

F7 0.9391 0.9876 0.9391 0.7278 0.6592

F8 0.9927 0.8968 0.9927 0.7358 0.6607

F9 0.9791 0.9777 0.9791 0.7515 0.6469

F10 0.9769 0.9782 0.9769 0.7199 0.6638

F11 0.9662 0.9809 0.9662 0.6677 0.6688

F12 0.9868 0.9859 0.9868 0.6588 0.6871

F13 0.9952 0.9295 0.9952 0.6819 0.6860

F14 0.9521 0.9825 0.9521 0.8449 0.5836

F15 0.9506 0.9863 0.9506 0.8084 0.6097

F16 0.9908 0.9417 0.9908 0.5413 0.7756

F17 0.9896 0.9795 0.9896 0.6859 0.6805

F18 0.8992 0.9827 0.8992 0.8447 0.5784

F19 0.8993 0.9849 0.8993 0.7637 0.6315

F20 0.9156 0.9891 0.9156 0.7973 0.6116

F21 0.9224 0.9896 0.9224 0.7778 0.6214



In controlled or sustained release formulations diffusion, swelling and erosion are the

three most important rate controlling mechanism followed. The drug release from the

polymeric system is mostly by diffusion and best described by fickian diffusion. But in

case of formulations containing swelling polymers, other processes include relaxation of

polymers chain, imbition of water causing polymers to swell and changing them from

initial glassy to rubbery state. Due to swelling considerable volume expansion takes place

leading to moving diffusion boundaries complicating the solution of Fick’s second law of

diffusion. So to explore the release pattern, results of the in vitro release data were fitted

to Korsmeyer and Peppas equation (Mt/M∞=ktn, where Mt/M∞is the fraction of drug

released after time t in respect to amount of drug released at infinite time, k is the rate

constant and n is the diffusion exponent) which characterize the transport mechanism.

When the regression coefficient ‘r’ value of zero order and first order plots were

compared, it was observed that the ‘r’ values of zero order were in the range of 0.89 to

0.99 whereas the ‘r’ values of first order plots were found to be in the range of 0.79 to

0.98 indicating drug release from all the formulations were found to follow zero order

kinetics.

The good fit of the Higuchi model to the dissolution profiles of all the formulations

suggested that diffusion is the predominant mechanism limiting drug release since the ‘r’

values of Higuchis plots were nearer to unity.

The invitro dissolution data as log cum percent drug release versus log time were fitted to

Korsmeyer et al equation, values of the exponent ‘n’ was found to be in the range of 0.54

to 0.84 indicating that the drug release is by Non-Fickian diffusion or anomalous

diffusion mechanism.

Documents

4: Analytical Profile of Aceclofenac - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/28939/15/15...Result and Discussion Department of Pharmaceutical Sciences, Bhagwant University,