4: analytical profile of aceclofenac -...
TRANSCRIPT
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.
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 97
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 98
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 99
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.
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 100
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 101
Fig. 4.4 IR spectrum of Aceclofenac
Fig. 4.5 IR Spectra of mixture of Drug and HPMC K4M
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 102
Fig. 4.6 IR Spectra of mixture of Drug and Carbopol 934P
Fig. 4.7 IR Spectra of mixture of Drug and Carbopol 971P
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 103
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 104
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 105
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 106
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 107
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 -
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 108
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 109
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.
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 110
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 111
Table 4.10 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 F6 F7 F8 F9 F10
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
Zero Order Dissolution Release Profile of Aceclofenac from F6-F10
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 112
Table 4.11 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 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
Zero Order Dissolution Release Profile of Aceclofenac from F11-F15
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 113
Table 4.12 Zero Order Dissolution Release Profile of Aceclofenac from F16-F21
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
Zero Order Dissolution Release Profile of Aceclofenac from F16-F21
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 114
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 115
Table 4.14 First Order Dissolution Release Profile of Aceclofenac from F6-F10
Time(hr)
Log Cumulative Percent Drug Retain F6 F7 F8 F9 F10
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
Fig: 4.15 First Order Dissolution Release Aceclofenac from F6-F10
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 116
Table 4.15 First Order Dissolution Release Profile of Aceclofenac from F11-F15
Time(hr)
Log Cumulative Percent Drug Retain F11 F12 F13 F14 F115
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
First Order Dissolution Release Profile of Aceclofenac from F11-F15
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
Fig: 4.16 First Order Dissolution Release Aceclofenac from F11-F15
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 117
Table 4.16 First Order Dissolution Release Profile of Aceclofenac from F16-F21
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
First Order Dissolution Release Profile of Aceclofenac from F16-F21
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 118
Table 4.17 Higuchi Model Representing Release Profile of Aceclofenac from F1- F5
SQRTof
Time (hr)
Cumulative Percent Drug Release F1 F2 F3 F4 F5
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 119
Table 4.18 Higuchi Model Representing Release Profile of Aceclofenac from F6- F10
SQRTof
Time(hr)
Cumulative Percent Drug Release F6 F7 F8 F9 F10
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
Higuchi Model Representing Release Profile of Aceclofenac from F6- F10
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
Fig: 4.19 Higuchi Model Representing Release Profile of Aceclofenac from F6- F10
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 120
Table 4.19 Higuchi Model Representing Release Profile of Aceclofenac from F11- F15
SQRTof
Time(hr)
Cumulative Percent Drug Release F11 F12 F13 F14 F15
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
Higuchi Model Representing Release Profile of Aceclofenac from F11- F15
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)
Fig: 4.20 Higuchi Model Representing Release Profile of Aceclofenac from F11- F15
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 121
Table 4.20 Higuchi Model Representing Release Profile of Aceclofenac from F16- F21
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
Higuchi Model Representing Release Profile of Aceclofenac from F16- F21
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
Fig: 4.21 Higuchi Model Representing Release Profile of Aceclofenac from F16- F21
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 122
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 123
Table 4.22 Korsmeyer Model Representing Release Profile of Aceclofenac from F6- F10
Log
Time (hr)
Log cumulative percentage of drug released F6 F7 F8 F9 F10
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
Korsmeyer Model Representing Release Profile of Aceclofenac from F6- F10
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
Fig: 4.23 Korsmeyer Model Representing Release Profile of Aceclofenac from F6- F10
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 124
Table 4.23 Korsmeyer Model Representing Release Profile of Aceclofenac from F11- F15
Log
Time (hr)
Log cumulative percentage of drug released F11 F12 F13 F14 F15
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
Korsmeyer Model Representing Release Profile of Aceclofenac from F11- F15
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
Fig: 4.24 Korsmeyer Model Representing Release Profile of Aceclofenac from F11- F15
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 125
Table 4.24 Korsmeyer Model Representing Release Profile of Aceclofenac from F16- F21
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
Korsmeyer Model Representing Release Profile of Aceclofenac from F16- F21
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
Fig: 4.25 Korsmeyer Model Representing Release Profile of Aceclofenac from F16- F21
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 126
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 127
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.
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 128
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
Result and Discussion
Department of Pharmaceutical Sciences, Bhagwant University, Ajmer 129
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.