See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/256089816

Formulation Design & Development of Piroxicam Emulgel

Article  in  International Journal of PharmTech Research · July 2012

CITATIONS READS

29 2,359

3 authors, including:

Dignesh Khunt Ashish Mishra

niper a Maliba Pharmacy College
22 PUBLICATIONS   222 CITATIONS    9 PUBLICATIONS   33 CITATIONS   

SEE PROFILE SEE PROFILE

All content following this page was uploaded by Dignesh Khunt on 27 February 2016.

The user has requested enhancement of the downloaded file.

 International Journal of PharmTech Research
CODEN (USA): IJPRIF ISSN : 0974-4304
Vol.4, No.3, pp 1332-1344, July-Sept 2012

Formulation Design & Development of Piroxicam

Emulgel
Dignesh M. Khunt*, Ashish D. Mishra, Dinesh R. Shah.

Department of Pharmaceutics, Maliba Pharmacy College, Bardoli 394601,

Gujarat, India

*Corres.author: [email protected]
Mobile No. :- 91-9724825126

Abstract: The objective of this work is to develop emulgel of piroxicam which will increase skin penetration
of drug in comparison with present marketed preparations of the drug. Based on solubility studies oleic acid as
oil, Tween-80 and Span-80 as emulsifiers and propylene glycol and cetostearyl alcohol as co-surfactant were
selected for preparation of emulgel. The emulgels were prepared using different combinations of oil,
emulsifiers, co-surfactant and carbomer (Carbompol 940 and Carbopol 934). They were optimized using 32 full
factorial designs to study the effect of independent variables, i.e. concentration of emulsifiers (X1) and carbomer
(X2) on dependent variables like % drug release at 2 and 6 hours. The prepared emulgels were evaluated in
terms of appearance, average globule size, drug content and in-vitro drug release. In-vitro release study
demonstrated diffusion controlled release of piroxicam from formulation up to 8 hours. The drug release profile
exhibited zero order kinetics. From the regression analysis, it was observed that all three independent variables
had significant effect on response variables. Formulation was optimized using contour plot and response surface
plot. The optimized formulations were found to be F3 and F12 containing lower concentration of Carbopol (0.5
%) and higher concentration of emulsifiers (6%). The optimized formulae ware evaluated for Zeta Potential,
viscosity, spreadability, skin permeation and stability. Skin permeation (%) of optimized batches (F3 and F12)
in 24 hours was found to be 87.89% and 89.09 % respectively. The formulation batch F12 had better anti-
inflammatory activity than marketed preparation.
Keywords: Piroxicam, Emulgel, Carbopol.

Introduction topical application, some studies have been carried

out to predict the percutaneous absorption of
Piroxicam is a non-steroidal anti-inflammatory piroxicam using different substances as permeation
compound with analgesic and antipyretic effects, enhancers5-10.
used for the treatment of rheumatoid arthritis, Many widely used topical agents like ointments,
osteoarthritis and traumatic contusions. It is well creams, lotions have numerous disadvantages. They
absorbed following oral administration however its are usually very sticky causing uneasiness to the
use has been associated with a number of patient when applied. Moreover they also have less
undesirable side effects on the stomach and kidneys spreading coefficient and need to apply with
in addition to gastric mucosal damage1,2. Dermal rubbing. They also exhibit the problem of stability.
delivery is an alternative route but requires a Due to all these factors, within the major group of
formulation which ensures deep skin penetration, semisolid preparations, the use of transparent gels
allowing therapeutic effect at localized site3,4.
Although piroxicam is not easily absorbed after
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1333

has increased both in cosmetics and in Tween-80, methyl salicylate and propyl paraben
pharmaceutical preparations11,12. were purchased from S.D Fine Chemicals Ltd.,
A gel is colloid that is typically 99% by weight Mumbai (India) All other chemicals and reagents
liquid, which is immobilized by surface tension used were of analytical grade. Deionized distilled
between it and a macromolecular network of fibers water was used throughout the study.
built from a small amount of a gelating substance
present. In spite of many advantages of gels a major Methods
limitation is their inability to delivery hydrophobic Solubility study
drugs12. An excess amount of piroxicam was added to each
To overcome this limitation an emulsion based solvent and was stirred magnetically. After stirring
approach is being used so that a hydrophobic for 24 hours at 37ºC, the equilibrated sample was
therapeutic moiety can be successfully incorporated centrifuged for 10 min at 5000 rpm (rotations per
and delivered through gels. When gels and minute) to remove excess amount of piroxicam. The
emulsions are used in combined form the dosage supernatant was filtered and properly diluted with
forms are referred as emulgels. phosphate buffer pH 7.4. The concentration of
Emulgels for dermatological use have several piroxicam was determined by UV
favorable properties such as being thixotropic, spectrophotometry10.
greaseless, easily spreadable, easily removable,
emollient, non-staining, transparent with long shelf Preparation of emulgel
life & pleasing appearance12. The composition of piroxicam emulgel formulations
The aim of this work was to develop an emulgel is shown in table II and III. First cetostearyl alcohol
formulation of piroxicam using two different grades is melted which was then mixed with oil, surfactant,
of carbomer (Carbopol 934 and Carbopol 940). The co-surfactant and methyl salicylate in required
influence of type and concentration of the gelling quantity. Then 0.5% piroxicam gel was dissolved in
agent and the emulsifying agent on the release of the this oil phase. Carbopols in required quantity as
drug from the prepared emulgels was investigated given in formulation table IV and V were dispersed
using 32 full factorial design. in water phase. Both the oily and aqueous phases
were separately heated to 50° to 60°C: then the oily
Materials and Methods phase was added to the aqueous phase with
continuous stirring (up to 2 hours). The pH was
Materials adjusted to 6 to 7 using triethanolamine.
Piroxicam was received as a gift sample from
Torrent Pharmaceutical Ltd, Ahmadabad (India).
Carbomers were purchsed from Corel Pharma
Chem., Ahmadabad (India). Oleic acid, Span-80,

Table I. Selection of independent and dependent variables

Independent variables Variable level
Low (-1) Medium (0) High (1)
Concentration of Emulsifiers (X1) 2 4 6
Concentration of Carbopol (X2) 0.5 0.75 1.0
Dependent variables
1. % Cumulative release at 2 hours (Q2 in %)
2. % Cumulative release at 6 hours (Q6 in %)
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1334

Table II. Formulation of ingredients of emulgel using Carbopol 940

Ingredients(%w/w) F1 F2 F3 F4 F5 F6 F7 F8 F9
Drug (%) 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Oleic acid (%) 20 20 20 20 20 20 20 20 20
Propylene glycol (%) 5 5 5 5 5 5 5 5 5
Methyl salicylate (%) 10 10 10 10 10 10 10 10 10
Cetostearyl alcohol (%) 4 4 4 4 4 4 4 4 4
Span-80 (%) 0.9 1.9 2.8 0.9 1.9 2.8 0.9 1.9 2.8
Tween-80 (%) 1.1 2.1 3.2 1.1 2.1 3.2 1.1 2.1 3.2
Carbopol 940 (%) 0.5 0.5 0.5 0.75 0.75 0.75 1 1 1
Water (%) 58.9 57.9 56.8 58.9 57.9 56.8 58.9 57.9 56.8
Propyl paraben 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02
Triethanolamine (%) Adjust pH 6 to 7

Table III. Formulation of ingredients of emulgel using Carbopol 934

Ingredients(%w/w) F10 F11 F12 F13 F14 F15 F16 F17 F18
Drug (%) 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Oleic acid (%) 20 20 20 20 20 20 20 20 20
Propylene glycol (%) 5 5 5 5 5 5 5 5 5
Methyl salicylate (%) 10 10 10 10 10 10 10 10 10
Cetostearyl alcohol (%) 4 4 4 4 4 4 4 4 4
Span-80 (%) 0.9 1.9 2.8 0.9 1.9 2.8 0.9 1.9 2.8
Tween-80 (%) 1.1 2.1 3.2 1.1 2.1 3.2 1.1 2.1 3.2
Carbopol 940 (%) 0.5 0.5 0.5 0.75 0.75 0.75 1 1 1
Water (%) 58.9 57.9 56.8 58.9 57.9 56.8 58.9 57.9 56.8
Propyl paraben 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02
Triethanolamine (%) Adjust pH 6 to 7

Table IV. In-vitro drug release study conditions

Apparatus Franz diffusion cell
Diffusion medium (in receptor compartment ) pH 7.4 phosphate buffer
Diffusion medium volume 15 ml
Temperature 37 ± 0.5ºC
Speed 50 rpm
Sampling volume 3 ml
Sampling interval 1 hour

Table V. Experimental design for animal study

No. Group
1 Control group Carrageenan (1%)
2 Standard group Topical application of marketed formulation (Pirox gel, Cipla) on inflamed
area (localized delivery)
3 Standard group Topical application of marketed formulation (Pirox gel, Cipla) on dorsal
area (transdermal delivery)
4 Test group Topical application of F12 batch on inflamed area (localized delivery)
5 Test group Topical application of F12 batch on dorsal area (transdermal delivery)
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1335

Experimental design Peppas models to ascertain the kinetics of the drug

release13,14.
A 32 level factorial design was conducted to study
the effect of independent variables (i) Concentration Optimization of formulation
of emulsifiers (X1) and (ii) Concentration of It was done by contour plot and response surface
Carbopol (X2) on dependent variables % cumulative plot using Design Expert software 8.0.7.1 trial.
drug release at 2 hour (Q2) and % cumulative drug Characterization of optimized batch
release at 6 hours (Q6). The independent and Optimized batch was evaluated for all parameters
dependent variables are listed in table I while all the previously described.
batches ware prepared according to the experimental Additional evaluation parameters of optimized batch
design (table II). are given below.
Two grades of Carbopol were taken. Same
experimental design was applied for both grades. Viscosity
Eighteen piroxicam emulgel formulations were The Viscosity of emulgel was carried out with
prepared in all. Brookfield viscometer (LVDV II + prime model)
using S64 spindle. The viscosity was measured at 12
Characterization of emulgel rpm.
Appearance
Appearance of gel was evaluated on the bases of Globule Size and Zeta Potential
visual inspection. Globule Size and Zeta Potential of emulsions were
determined by Zetatrac. Zetatrac determines Zeta
Drug content Potential by measuring the response of charged
Drug content of emulsion was measured by UV particles to an electric field.
spectrophotometer. 1 ml of emulsion was diluted to In a constant electric field particles drift at a constant
20ml with methanol and volume was made up to velocity. Through the velocity, the charge and Zeta
100ml using phosphate buffer 7.4. A volume of 2ml Potential are determined. Zetatrac utilizes a high
of this solution was further diluted to make 10 μg/ml frequency AC electric field to oscillate the charged
solution of piroxicam. particles. The Brownian motion power spectrum is
analyzed with the Nanotrac controlled reference
Average globule size technique of particle sizing to determine the
Average globule size was measured by light Modulated Power Spectrum, a component of the
microscope. power spectrum resulting from the oscillating
particles. Zeta Potential is calculated from the MPS
In-vitro drug release study signal. Also determined are the particle mobility
The in-vitro drug release of piroxicam from prepared (velocity per electric field), particle charge and
formulations and marketed formulation (Pirox Gel, particle size.
Cipla Pharmaceuticals) were studied through
cellophane membrane using Franz diffusion cell. Photomicrography
The cellophane membrane was previously treated Morphology of emulsion was studied under light
with sodium hydroxide and soaked overnight in the microscope. Optimized batches of the emulgel were
phosphate buffer 7.4 at refrigeration temparature. viewed under light microscope to study their shape.
The treated cellophane membrane was sandwiched The emulgel was suitably diluted, mounted on glass
between donor and receptor compartments of Franz slide and viewed by light microscope under
diffusion cell. Formulation equivalent to 2 mg of magnification of 40 X.
piroxicam was added on the cellophane membrane.
A magnetic bar was continuously stirred in diffusion Skin permeation and skin retention study
medium to avoid diffusion layer effect. The Skin permeation study was carried out with rat
withdrawn sample was analyzed by UV dorsal skin using modified Franz diffusion cell by
spectrophotometer. Study conditions were as shown the same method as described above in the in-vitro
in the table IV. drug release study of emulgel. The skin was
carefully checked through a magnifying glass to
Kinetic study and mechanism of drug release ensure that samples were free from any surface
The diffusion profile of all the batches was fitted to irregularity such as tiny holes or crevices in the
Zero order, First order, Higuchi and Krosmeyer- portion that was used for permeation studies.
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1336

The ability of emulgel to help retain the drug within The % inhibition of paw edema in drug treated
the skin (i.e. depot-effect) was investigated by group was compared with carregenan control group
determining the amount of drug retained in the skin and calculated according to the formula:
samples employed in permeation studies. For this, % inhibition of drug = Dc-Dt/ Dc x 100
remaining emulgel from the donor compartment was
pipette out and dissolved in phosphate buffer. Where, Dc = Rat paw diameter (in mm) of control
Absorbance was measured by UV group.
spectrophotometer to determine amount of drug Dt = Rat paw Diameter of test group
retained and remaining to diffuse.
Stability study
Spreadability Stability study of selected formulation was done at
One of the criteria for an emulgel to meet the ideal room temperature for 1 month and formulation was
quantities is that it should possess good finally evaluated for appearance, drug content and
spreadability. It is the term expressed to denote the pH.
extent of area to which gel readily spreads on
application to skin or affected part. The therapeutic
efficacy of a formulation also depends upon its Result and discussion
spreadability. Solubility
Spreadability of emulgel and marketed gel was Solubility in various excipients is shown in table VI.
measured in terms of diameter of emulgel circle From data shown in Table VI, highest solubility of
produced when emulgel is placed between two glass piroxicam was found in oleic acid amongst oils,
plates of definite weight. A weighed quantity (350 Tween 80 amongst surfactants and propylene glycol
mg) of emulgel or gels was taken on one glass plate amongst co-surfactants. Hence these components are
and another glass plate was dropped from a distance selected for preparation of emulgel system.
of 5 cm. The diameter of the circle of spread
emulgel was measured15,16. Appearance of emulsions and emulgels
All formulation batches were found to be
In-vivo Anti- inflammatory activity homogenous yellowish milky emulsions while
All the experimental procedures were carried out in emulgels were found to be yellowish white viscous
accordance with committee for purpose of creamy preparation.
experiments on animal’s guidelines (CPSCEA). The
study was reviewed and approved by Institutional Drug content
Ethics Committee (Protocol number: MPC/16/2012), Drug content details of emulgel are shown in table
Maliba Pharmacy College, India. VII. Amount of drug in the emulgel indicates the
Edema was induced on the left hind paw of the rats suitability of the system for high entrapment in the
by subplantar injection of 1 %( w/v) carrageenan. internal phase.
They were divided into 5 groups of 5 rat each (table
V). Formulations i.e. F12 and standard (Pirox gel, Average globule size
Cipla) containing 0.25 mg of piroxicam were Average globule size measurements are shown in
applied after carrageenan administration17, 18. table VII. The results indicate that globule size of
The area to which gels were applied was kept droplet varies from 11 to 17 µm.
constant (1 cm2). The paw thickness was measured
at intervals of 30, 90, 180, 360 and 1440 minute by
measurement of diameter using Vernier callipers.

Table VI. Solubility study data

Components Solubility (mg/ml)
Water 0.13
Linseed oil 5
Oleic acid 13.2
Phosphate buffer 7.4 0.20
Propylene glycol 6
Tween 80 16
Span 80 3.2
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1337

Table VII. % Drug content and average globules size

% Drug Average Average globules
Batch Batch % Drug Content
Content globules size size (µm)
No. No. (n=3)
(n=3) (µm) (n=50) (n=50)
F1 98.29 ± 0.5 15.5 ± 0.25 F10 97.38 ± 0.64 13.42 ± 1.04
F2 97.21± 0.9 17 ± 0.75 F11 99.24 ± 1.43 12.75 ± 2.12
F3 101.23± 1.0 15 ± 1.0 F12 97.98 ± 2.29 11 ± 0.47
F4 99.01± 0.7 16.37 ± 0.35 F13 99.41 ± 0.28 11.9 ± 0.4
F5 97.69± 0.8 13.12 ± 1.06 F14 101.77 ± 2.88 12.75 ± 0.32
F6 100.13± 0.99 11.38 ± 0.56 F15 98.95 ± 0.83 12.5 ± 1.25
F7 99.1 ± 0.42 11 ± 0.95 F16 101.45 ± 1.66 12.9 ± 0.18
F8 102.59 ± 1.54 12.5 ± 1.25 F17 100.11 ± 1.75 12.5 ± 0.95
F9 101.7± 0.35 12.9 ± 1.3 F18 102.54 ± 0.59 12.1 ± 2

In-vitro drug release Y1= 14.52 + 3.66 X1 – 6.282 X2 + 1.01 X12 – 0.525
The results of in-vitro drug release study are shown X22 -0.8425 X1X2
in table VIII and comparative drug release is shown
in figure 1. The amount of drug released at 2 hr from the F10-
Formulation batches F3 and F12 release drug faster F18 batches of emulgel varied from 14.41% to
than the other formulation due to the lower 22.42%. Correlation coefficient was found be 0.940
concentration of Carbopol and higher cocentration suggesting best fit to model. From the P-value, it can
of emulsifiers. An increase in concentration of be concluded that X1 and X2 have the prominent
Carbopol leads to decreased drug release from effect (P < 0.05) on the Q2. Postive sign of X1 in
formulation due to increase in viscosity of regression equation indicates that the response value
formulation. increases as the number of factors increases.
Negative sign of X2 in regression equation indicates
Kinetic study and mechanism of drug release that the response value decreases as the number of
The correlation coefficient value (R2) of each factors increases.
formulation for zero order, first order, Higuchi, Y2 = 60.327 + 5.183 X1 – 3.377 X2 + 0.91 X12 -0.57
Hixon Crowell and value of release exponent from X22 – 0.405 X1X2
Korsmeyer Peppas model are shown in table IX.
The release kinetics data indicates that the release of The amount of drug released at 6 hr from the F1-F9
drug from emulgels follows zero order kinetics batches of emulgel varied from 52.52% to 69.64%.
because the correlation coefficient values are higher Correlation coefficient was found to be 0.9994
in case of zero order equation. The release rate is suggesting best fit to model. From the P-value, it can
independent of the concentration of the drug. The be concluded that X1 and X2 have the prominent
release exponent value of Korsmeyer Peppas effect (P < 0.05) on the Q6. Postive sign of X1 in
equation is near to 1, this suggests that the emulgel regression equation indicates that the response value
follows case II transport mechanism (zero order increases as the number of factors increases.
release). Negative sign of X2 in regression equation indicates
that the response value decreases as the number of
Data analysis of 32 full factorial design factors increases.
Multiple regression analysis of F1-F9 batches are Similar results were found for F10-F18 bathes,
shown in table X. multiple regression analysis of which is given in
The response (Y1 and Y2) obtained at table XI.
various levels of the 2 independent variables (X1 and
X2) were subjected to multiple regression to yield a
second-order polynomial equation (full model).
Equation clearly reflects the wide range of values for
response (Y1 and Y2).
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1338

Table VIII (a) In-vitro drug release of F1-F9 and marketed formulation (n=3)
% Cumulative drug release
Time
Pirox
(hours) F1 F2 F3 F4 F5 F6 F7 F8 F9
gel
1 8.02 6.31 11.77 2.41 5.56 11.69 2.39 5.80 6.14 10.19
2 17.64 20.32 24.89 10.66 13.41 21.50 6.25 8.78 10.13 22.90
3 27.54 26.76 32.59 18.93 23.29 31.39 20.49 21.51 22.48 35.80
4 40.43 40.93 45.41 32.76 37.05 38.38 34.42 35.57 36.83 45.26
5 49.26 54.61 57.47 43.53 50.31 48.27 43.96 45.71 49.91 51.96
6 58.49 63 69.73 56 60.56 66.24 52.53 56.28 62.15 67.23
7 71.82 76.45 80.40 72.52 75.82 78.07 72.08 76.04 78.33 76.35
8 87.29 89.23 92.61 86.84 88.03 90.24 83.24 85.89 88.69 88.24

Table VIII(b) In-vitro drug release of F9-F18 and marketed formulation (n=3)
Time % Cumulative drug release
(hours) F10 F11 F12 F13 F14 F15 F16 F17 F18
1 10.27 9.58 11.28 8.65 10.10 9.54 6.39 5.98 8.41
2 19.16 20.76 22.20 17.73 19.23 21.87 14.70 16.71 17.98
3 30.91 27.48 31.24 30.72 31.65 29.68 23.59 27.83 29.41
4 39.03 39.62 42.24 39.99 40.34 40.23 34.52 38.19 40.38
5 46.53 48.38 52.74 48.33 48.75 51.54 43.83 46.10 47.10
6 58.60 62 65.42 57.56 60 63.87 55 58.54 61.63
7 73.25 73.54 79.46 71.31 74.75 76.85 61.78 72.56 76.51
8 88.33 89.18 93.93 86.32 87.84 90.06 84.66 86.73 87.86

Table IX Kinetics and release mechanism of F1-F18 and marketed formulation

R2 Value Release
Batch Hixon Korsemeyer exponent
Zero order First order Higuchi
Crowell Peppas ‘n”
F1 0.994 0.918 0.963 0.936 0.998 1.123
F2 0.996 0.876 0.973 0.9525 0.985 1.266
F3 0.998 0.924 0.975 0.948 0.996 0.975
F4 0.989 0.872 0.944 0.928 0.991 1.74
F5 0.995 0.915 0.959 0.947 0.998 1.36
F6 0.987 0.956 0.945 0.926 0.990 0.926
F7 0.988 0.871 0.950 0.945 0.979 1.836
F8 0.985 0.929 0.941 0.937 0.960 1.366
F9 0.990 0.929 0.952 0.947 0.972 1.368
F10 0.987 0.943 0.947 0.915 0.997 0.967
F11 0.991 0.938 0.953 0.924 0.995 1.01
F12 0.994 0.945 0.957 0.908 0.999 0.968
F13 0.992 0.915 0.963 0.936 0.996 1.07
F14 0.993 0.933 0.959 0.935 0.998 0.997
F15 0.995 0.926 0.962 0.936 0.996 1.03
F16 0.980 0.924 0.939 0.903 0.999 1.20
F17 0.994 0.891 0.962 0.937 0.993 1.26
F18 0.993 0.923 0.959 0.940 0.998 1.10
Pirox gel 0.996 0.892 0.981 0.962 0.993 1.207
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1339

Table X. Multiple regression analysis for Y1 and Y2 (Full model) (batch F1-F9)
Q2 = Y1 Q6= Y2
Dependent variables P value Coefficients P value Coefficients
Intercept 0.002526 14.52 3.99*10-8 60.327
X1 0.005007 3.66 3.73*10-5 5.183
X2 0.022568 -6.282 1.03*10-5 -3.377
X3 0.743054 1.01 0.032117 0.91
X4 0.538926 -0.525 0.009023 -0.57
X5 0.474354 -0.8425 0.031719 -0.405

Table XI. Multiple regression analysis for Y1 and Y2 (Full model) (batch F10-F18)
Q2 = Y1 Q6= Y2
Dependent variables P value Coefficients P value Coefficients
Intercept 1.21*10-5 19.58778 1.85*10-07 60.36556
X1 0.002699 1.745 0.000185 3.293333
X2 0.001525 -2.12 0.001103 -1.80833
X3 0.914296 0.038333 0.553409 0.166667
X4 0.051985 -1.02667 0.347551 -0.27833
X5 0.812491 0.06 0.805951 -0.0475

Results of Analysis of variance (ANOVA) and F12 batches were selected as optimized batches
ANOVA was done using Microsoft Excel. Results exacting the maximum drug release from the
of ANOVA for Q2 and Q6 are shown in Table XII. emulgel formulation.

Contour plot and response surface plot

Results of contour plot and response surface plot are
shown in figure 1(a) and figure 1(b). From this F3

Table XII. ANOVA for dependent variables for F1-F18

Sum of Degrees of Significance
Source Mean Square F Value
Squares Freedom F
For Q2 = % drug release at 2 hours (F1-F9)
Regression 322.5603 5 64.51206 15.12272 0.024448
Residual 12.79771 3 4.265903 - -
Total 335.358 8 - - -
For Q6 = % drug release at 6 hours (F1-F9)
Regression 232.575 5 46.51501 1030.867 4.76*10-05
Residual 0.135367 3 0.045122
Total 232.7104 8
For Q2 = % drug release at 2 hours (F10-F18)
Regression 47.36198 5 9.472396 44.0774 0.005220422
Residual 0.644711 3 0.214904 - -
Total 48.00669 8 - - -
For Q6 = % drug release at 6 hours (F10-F18)
Regression 84.9162 5 16.98324 135.3296 0.000992
Residual 0.376486 3 0.125495 - -
Total 85.29269 8 - - -
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1340

Figure 1 (a) Counter plot and Response surface plot for F1-F9

Figure 1 (b) Counter plot and Response surface plot for F1-F9
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1341

Evaluation of Optimization Globule Size and Zeta Potential

The results of Globule size and Zeta Potential
Viscosity of optimization batch measurement of the batch F3 and F12 emulgels are
Viscosity of the emulgel was measured at 12 rpm. shown in figure 2 (a, b). Results revealed that both
Viscosity of F3 and F12 was found to be 21445 ± batches had reasonable globule size and PDI
0.59 cp and 19446 ± 0.74 cp respectively. (Polydispersibility index).

Figure 2 (a) Globule Size and Zeta Potential of F3

Figure 2 (b) Globule Size and Zeta Potential of F12

Photomicrography Though this study does not give any exact estimate
The suitably diluted emulsions of optimized batches of size however it gives a general idea about
(F3 and F12) were observed under light microscope formation of emulsion and success of the method
at 40X (figure 3). From the photomicrograph, nearly used.
spherical globules of emulsion were observed.
Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1342

Figure 3 Photomicrographs of F3 and F12

Skin permeation and skin retention study parameter. Results of spreadability indicate that
The skin permeation of Piroxicam from the spreadability of emulgel is better than the marketed
optimized emulgel was studied through the rat’s gel.
dorsal skin using a modified Franz diffusion cell.
The diffusion medium used was phosphate buffer In-vivo study of the emulgels (Anti-inflammatory
pH 7.4. The result of skin permeation for 24 hours of activity)
emulgel is as shown in figure 4. This study was conducted by applying emulgel F12
Optimized batch F3 and F12 the amount of drug topically at site of inflammation and also at a site
permeated through skin in 24 hours was 87.89% and away from inflammation (transdermal application)
89.09 %. In marketed formulation, skin permeation because emulgels were exhibiting high in-vitro
was found to be 60.56% where as drug retention in release in comparison to marketed formulation
skin was found to be 28 %. It can be concluded that whereas skin retention was found to be negligible in
drug permeation is enhanced in the emulgels. emulgels. The anti-inflammatory action of
formulation F12 was calculated and it was compared
Spreadability with marketed preparation (Pirox gel, Cipla). The %
Spreadability of the formulations is shown in table inhibition of marketed formulation and F12 are
XIII. Spreadability of emulgel is an important given in table figure 5.

100
Cumulative % drug permeated

90
80
70
60
50 F3
40 F12
30
Pirox Gel (M)
20
10
0
0 10 20 30
Time (hours)

Figure 5. % Inhibition of inflammation

Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1343

Table XIII Spreadability of the formulation

Batch Diameter of circle (mean ± s.d. , n=3)
F3 3.13 ± 0.11
F12 3.77 ± 0.20
Marketed formulation 2.27 ± 0.25

Table XIV Results of stability study (mean ± s.d., n=3)

Before After
Appearance pH Drug content Appearance pH Drug content
(%) (%)
yellowish 6.29 ± 0.53 99.45 ± 1.23 yellowish 6.96 ± 0.73 98.00±0.64
white viscous white viscous
creamy creamy

Results show that the F12 formulation is more levels and 2 factors. From the polynomial equation
effective in inhibiting inflammation than marketed and contour plots generated, both independent
formulation. It is effective topically as well as factors showed significant effect on dependent
transdermally. variables. The release of Piroxicam was good fit to
the zero order and Higuchi model. The formulation
Stability study batch F12 showed better anti-inflammatory activity
Stability study was performed on optimized batches than marketed preparation. Thus emulgel of
F3 and F12 at ambient conditions. The results Piroxicam is suitable to dermal delivery.
obtained after 1 month time period are shown in
table XIV. Acknowledgements
We would like to thank Dr. Bhavin Vyas and Mr.
Conclusion
Shrikant Joshi (Faculty of Pharmacology, Maliba
The present investigation deals with the formulation Pharmacy College, India) for their kind help in
design and development of emulgel of piroxicam. conducting animal study.
Optimization was done using factorial design at 3

References the In-vitro percutaneous absorption of

piroxicam to optimise the formulation of patch
1. Sean C Sweetman; Martindale the Complete tests in dermatology. Drug Development
Drug Reference: the Pharmaceutical Press, Research. 2003, 58: 283–90.
2009, 117-8. 7. Santoyo S, Ygartua P; Effect of skin
2. Klaus Florey; Analytical Profile of Drug pretreatment with fatty acids on percutaneous
Substance: Elsevier, 15:511-30. absorption and skin retention of piroxicam after
3. Marks R, Dykes P; Plasma and cutaneous drug its topical application. European Journal of
levels after topical application of piroxicam gel: Pharmaceutics and Biopharmaceutics. 2000, 50:
a study in healthy volunteers. Skin Pharmacol. 245-50.
1994, 7: 340–4. 8. Curdy C, Yogeshvar N, Naik A, Richard H;
4. Monteiro-Rivier N, Imman, A, Riviere J; Piroxicam delivery into human stratum
Topical penetration of piroxicam is dependent corneum: in-vivo iontophoresis versus passive
on the distribution of the local cutaneous diffusion. Journal of Controlled Release, 2001;
vasculature. Pharm. Res. 1993, 10:1326–31. 76: 73–9.
5. Shin S, Cho C, Oh I; Enhanced efficacy by 9. Murthy S, Zhao Y, Sen A, Wen Hui S.
percutaneous absorption of piroxicam from the Cyclodextrin enhanced transdermal delivery of
poloxamer gel in rats. International Journal of piroxicam and carboxyfluorescein by
Pharmaceutics. 2000, 193: 213–8. electroporation. Journal of Controlled Release.
6. Ste´phanie d’Arpino, Archer V, Marty J, 2004, 99: 393–402.
Lantieri L, Vincent C; Influence of Vehicles on
 Dignesh M. Khunt et al /Int.J.PharmTech Res.2012,4(3) 1344

10. Okuyama H, Ikeda Y, Kasai S; Influence of non- 15. Desai K; Enhanced skin permeation of rofecoxib
ionic surfactants, pH and propylene glycol on using topical microemulsion gel. Drug
percutaneous absorption of piroxicam from Development and Research. 2004, 63: 33–40.
cataplasm. International Journal of 16. Bachhav Y, Patravale V; Microemulsion based
Pharmaceutics. 1999, 186: 141-148. vaginal gel of fluconazole: Formulation, in vitro
11. Rieger M, Lachman L, Lieberman H, Kanig J; and in-vivo evaluation. International Journal of
The Theory and Practice of Industrial Pharmacy: Pharmaceutics. 2009, 365: 175–9.
3rd ed. PA Lea and Febiger: Philadelphia: 1986, 17. Boughton‐Smith N, Deakin A, Follenfant R.
502-33. Whittle BJ, Garland LG; Role of oxygen
12. Khullar R, Saini S, Seth N, Rana A; Emulgels: radicals and arachidonic acid metabolites in the
A surrogate approach for topically used reverse passive Arthus reaction and carrageenin
hydrophobic drugs. International Journal of paw oedema in the rat. Br. J Pharmacol. 1993,
Pharmacy and Biological Sciences. 2011, 1: 110: 896‐902.
117-28. 18. Puri R, Sanghavi N. Evaluation of Topical
13. Dash S, Murthy P, Nath L, Chowdhury P; Non‐Steroidal Drugs of Using Penetration
Kinetic modeling of drug release from Enhancers. Indian Journal of Pharmacology.
controlled drug delivery systems. Acta Poloniae 1992, 24(4): 227‐8.
Pharmaceutical Drug Research. 2010, 67: 217-
23.
14. Costa P, Lobo M; Modeling and comparison of
dissolution profile. European Journal
Pharmaceutical Sciences. 2001. 13: 123-33.

*****

View publication stats