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“FORMULATION AND OPTIMIZATION OF ACECLOFENAC GEL”
MASTER OF PHARMACY DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA,
BANGALORE.
BY
ARUN GOKUL T.S
Under The Guidance of
Mr.KRISHNANANDA KAMATH K.
M. PHarm.,
DEPARTMENT OF QUALITY ASSURANCE
SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE – 574143
2011-2013
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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
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Name of the Candidate and Address: Mr. ARUN GOKUL T.S.
DEPT. OF QUALITY ASSURANCE,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
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Name of the Institution:
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Course of Study and Subject:
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Date of Admission:
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Title of the Project:
SRINIVAS COLLEGE OF
PHARMACY,
VALACHIL, FARANGIPETE POST,
MANGALORE-574143.
MASTER OF PHARMACY
(QUALITY ASSURANCE)
15 th JULY 2011
“FORMULATION AND OPTIMIZATION OF ACECLOFENAC GEL”.
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BRIEF RESUME OF THE INTENDED WORK:
6.1 INTRODUCTION :
The optimization of pharmaceutical formulations with regard to one or more
attributes has always been a subject of importance and attention for pharmaceutical
scientists in formulation research. The word optimized simply implies to make as
perfect, effective or functional as possible. Hence, optimization of a product or
process is the determination of the experimental conditions resulting in its optimal
performance.1
The delivery of drug through the skin has long been a promising concept because
of the ease of the access, large surface area, vast exposure to the circulatory and
lymphatic networks and non invasive nature of the treatment. The U.S.P. defines gels
as a semisolid system consisting of dispersion made up of either small inorganic
particle or large organic molecule enclosing and interpenetrated by liquid. Gels are
typically formed from a liquid phase that has been thickened with other components.1
Aceclofenac is a Non steroidal anti inflammatory drug(NSAID) having excellent
anti-inflammatory and analgesic activity but NSAID produces GIT ulceration, liver
and kidney trouble especially in case of oral administration. Aceclofenac is used in
treatment of Osteoarthritis, Rheumatoid arthritis, Acute lumbago, and Dental pain
condition. However like other NSAIDs, oral administration of this drug is also
associated with severe gastrointestinal side effects like ulceration and gastro intestinal
bleeding liver and kidney trouble. The solution of this problem lies in the fact that,
topically applied NSAIDs are safer than and as efficacious as oral NSAIDs.
Furthermore, the topical route of administration has a high patient compliance, which
derives from it being non-invasive and the long interval between applications. Topical
administration also provides a means to obtain constant systemic drug levels.5
Hence, the need of the study is two-fold, first to develop an Aceclofenac gel with
very good skin permeability of the drug. Second to develop a theoretical relationship
that may be used to optimize the gel formulation.
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6.2 – REVIEW OF LITERATURE:

Aukunuru J, Boneppally C, Guduri V
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prepared and optimized ibuprofen
ointment with a potential for both topical and systemic delivery of the drug. A
co-solvency technique with a trial and error approach was used to develop a
10% ibuprofen ointment in petrolatum base, with the entire drug dissolved in
the base. An insertion cell was used to evaluate drug release from the
formulations. Further, factorial design multiple regression (FDMRA) analysis,
a statistical optimization technique, was used in the optimization of the final
formulation. Best fit equations for optimization purposes including various
fluxes (initial, steady-state and total) and diffusion coefficient as dependent
variables and the concentrations of co-solvents as independent variables were
obtained using SAS programme. Dependent variables strongly depended
(p<0.05) on the independent variables and followed the polynomial equations
generated.

Rabia B, Muhammad HS, Nousheen A, Durriya H, Masud-ur-rehman
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have
formulated and optimized ibuprofen tablets by direct compression method. In
order to obtain the best, optimized product, nine different formulations were
developed. Diluents (X1), disintegrant (X2) and lubricant (X3) were taken as
independent variables. Weight variation (Y1), thickness (Y2), length and
width (Y3), hardness (Y4), friability (Y5), disintegration (Y6), Dissolution
(Y7) and pharmaceutical assay (Y8) were studied as response variables. The
results of all nine formulations were found within the acceptable limits
conforming to those given in official compendia. However, f-6 was selected as
an optimized product on the basis of high dissolution (99.05%) and assay
(100.04%).

Mathure DM, Bhalekar1 MR, Mathure DM, Padalkar RR, Dawane BS , Chobe
SS
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have formulated and statistically optimized controlled release pellets of
Cetrizine Dihydrochloride. The objective of this study was to formulate
controlled release pellets of Cetrizine dihydrochloride and optimize the effect
of formulation variables i.e. concentration of Eudragit RLPO and ethyl
cellulose. The experimental design selected was 32 full factorial designs using
these two variables. Drug release after 24 hr and t50% were evaluated as
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response parameters. Polymers were coated onto the drug loaded pellets using
pan coater. It was observed that the concentrations of polymers directly
affected the drug release profile. The effect of the variables and behaviour of
the system was studied using response surface plots. The optimized
formulation showed drug release of 96.22% in 24 hr and t50% of 11hr 54 min.
The results of this study revealed that the pellets of Cetrizine dihydrochloride
coated with 1:5 ratio of Eudragit RLPO: Ethyl cellulose showed optimum
controlled release.

Ajay S, Jolly P, Rajesh P4 have prepared and optimized Aceclofenac
Proniosomes using central composite design and carry out stability studies.
Three independent variables selected were molar ratio of drug to lipid (X1),
surfactant loading (X2) and volume of hydration (X3). Based on central
composite design, 16 batches of proniosomes were prepared by slurry method
and evaluated for the percentage drug entrapment (PDE) and mean volume
diameter (MVD). The PDE and MVD (dependent variables) and the
transformed values of independent variables were subjected to multiple
regressions to establish a second order polynomial equation. Contour plots
were constructed to further elucidate the relationship between the independent
and dependent variables. The conformity of the polynomial equations was
checked by preparing three checkpoint batches. From the computer
optimization process and contour plots, predicted levels of independent
variables X1, X2, and X3 (-0.77, -0.8 and 0 respectively), for an optimum
response of PDE with constraints on MVD were determined. The optimized
batch was subjected to stability studies. The polynomial equations and contour
plots developed using central composite design allowed us to prepare
proniosomes with optimum responses. Proniosomes stored refrigerated and at
room temperature, were both found to be stable.

Kashyap N, Jadon PS, Naruka PS, Chauhan CS 5 have formulated Aceclofenac
Gel Using Poloxamer 407. Poloxamer 407 is used primarily as a thickening
agent and gel former, but also as a co emulsifier and consistency enhancer in
creams and liquid emulsions. The Aceclofenac gels were prepared by using
different concentration of Poloxamer 407 for topical drug delivery with an
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objective to increase transparency and spreadability. The transparency of
prepared batch A9 was good as compared to the marketed gel. The percent
drug release was 97.11 and 98.66 from A9 and marketed gel respectively in
120 min. No irritation was observed by skin irritation test. Stability studies
under accelerated condition showed satisfactory results. It can be concluded
that Poloxamer 407 gel containing Aceclofenac showed good consistency,
homogeneity, spreadability and stability and has wider prospect for topical
preparations.

Bhosale UV, Kusumam Devi6 V have formulated and optimized mucoadhesve
Nano Drug delivery system of acyclovir. Acyclovir is an antiviral drug, used
for treatment of herpus simplx viral infection with an oral bio availability of
only 10-20%. Mucoadhesive polymeric nano drug delivery systems of
acyclovir have been designed and optimized using 23 full factorial designs.
Poly (lactic –co-glycolic acid) was used as polymer along with polycarbophil
as muco adhesive polymer and Pluronic F68 as stabilizer. From the
preliminary trials the constraints for independent variables X1 (amount of
PLGA), X2(amount of pluronic F68) and X3 (amount of poly carbophil) have
been fixed. The dependent variables that were selected for the study were
particle size (Y1), %drug entrapment (Y2), and % drug release in 12h (Y3).
The derived polynomial equations were verified by check point formulation.
6.3 OBJECTIVES OF THE STUDY:
1. To formulate and evaluate Aceclofenac gel with various concentration of base.
2. To optimize the prepared Aceclofenac gel using ‘ UNSCRAMBLER- CAMO ’
( Software for Multivariate data analysis )
6.4 MATERIALS AND METHODS:
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Materials:
1. Drug
:Aceclofenac
2. Gelling agent : Carbopol or Sodium CMC base
3. Excipients
: Linseed oil, Methyl salicylate, Menthol, Methyl paraben, SLS,
Isopropyl alcohol, Propylene glycol etc.
Methods:

Aceclofenac gel shall be prepared either by using carbopol base or by sodium
CMC base.

Selection of independent and dependent variables for optimization of the
formulation.

The prepared gel is then evaluated for pH, viscosity, membrane permeability
and Drug content studies will be carried out.

pH of gel can be determined using digital pH meter. About 2 gm of gel is
stirred in distilled water till a uniform suspension effected. The volume is then
make up to 40 ml and pH of solution is measured.8
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Viscosity of the gel can be measured by brook field viscometer.8

Drug content in the gel can be determined by taking 1 gm gel in a 100 ml
volumetric flask and dissolve with little amount of methanol and mixture is
shaken till solution is affected. The volume is made up to 100 ml with
methanol. The solution is filtered and further dilutes 5 ml to 500 ml with
methanol. The absorbance of solution is measured at 275 nm.8

The membrane permeability studies of various formulations of Aceclofenac
gel can be carried out using Kesharychien diffusion cell. The receptor
compartment is filled with saline phosphate buffer of pH 7.4 and methanol
(90:10) and keeps at 32±0.5oc stirred with the help of magnetic stirrer.
Methanol 10% is added to maintained sink condition. About 200-300mg of gel
is placed on cellulose chamber. One ml of sample is withdrawn from receptor
compartment at 1, 2, 3, 4, 5, 6, 7, 8 hour and replaced with same volume of
medium. All samples are diluted up to 10ml with medium and analysed at
275nm.9

Optimization by the use of ‘UNSCRAMBLER- CAMO ’software..
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7.1
SOURCE OF DATA:
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Review of literature from
a) Journals such as
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
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Journal of Chemical and Pharmaceutical Research
Indian Journal of Pharmaceutical Sciences
International journal of biopharmaceutical & toxicological research
Tropical Journal of Pharmaceutical Research
International journal of drug development and research.
b) Internet Browsing.


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www.pharmainfo.net
www.sciencedirect.com
www.rxlist.com
www.pubmed.com
www.medline.com
c) Laboratory based studies.
7.2
Method of Collection of Data:
1. An Overview of Aceclofenac gel.
2. Results of formulation and Evaluation of Aceclofenac gel using different
gelling agents.
3. Optimization results of formulated Aceclofenac gel using ‘UNSCRAMBLER
- CAMO ’ ( Software for Multivariate data analysis )
4. Results of statistical analysis data
7.3 Does the study require any investigations or interventions to be conducted
on patients or other humans or animals? If so, please describe briefly.
- Not applicable
7.4
Has ethical clearance been obtained from your institution in case of 7.3?
-
Not applicable
LIST OF REFERENCES:
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1. Aukunuru J, Boneppally C, Gunduri V. Preparation, Characterization and
Optimization of Ibuprofen ointment intended for Topical and Systemic delivery
Tro J Pharm Res 2007;6(4):855-60.
2.
Rabia B, Muhammad HS, Nousheen A, Durriya H, Masud-ur-rehman.
Formulation development and optimization of ibuprofen tablet by direct
compression method. Pak. J. Pharm. Sci 2008; 21(2):113-20.
3. Mathure DM, Bhalekar MR, Mathure DM, Padalkar RR, Dawane BS, Chobe
SS. Formulation and statistical optimization of controlled release pellets of
cetrezine dihydrochloride. Der Pharmacia Lettre 2011, 3(3):443-52.
4. Ajay S, Jolly P, Rajesh P. Preparation, Characterization, Optimization, stability
studies of Aceclofenac proniosomes. Iran j Pharm Res 2008; 7(4):237-46.
5. Kashyap N, Jadon PS, Chauhan CS, Naruka PS. Formulation development and
Characterization of Aceclofenac gel using Poloxamer 407. J.Chem.Pharm.Res
2010; 2(4):357-63.
6. Bhosale UV, Kusum Devi V. Formulation and Optimization of Mucoadhesive
nano drug delivery system of Acyclovir. Pharmbit 2010; XXII (2):94-104.
7. Shaji S, Pasha ST, Srinivasan S, Ray S. Design and Optimization of a
Multiparticulate gastro retentive dosage form for better control of gastric
activity. J Pharm Sci & tech 2009; 1(1):40-7.
8. Aijaz AS, Siddique SA, Siddique AR, Zahid Z. Formulation development and
Characterization of Aceclofenac gel containing linseed oil and ginger oleoresin.
Int J Pharma Tech Res 2011; 3(3):1448-53.
9. Japan P, Brijesh P, Kaushal P, Manish P. Formulation and evaluation of Topical
Aceclofenac gel using different gelling agents. Int J Drug Dev. & Res 2011;
3(1):156-64.
10. Ravi K, Patil MB, Sachin RP, Mahesh SP. Evaluation of anacardium
occcidetale gum as gelling agent in Aceclofenac gel. Int.J. PharmTech Res
2009, 1(3):695-703.
11. Sundar LT, Sunny K, Kapil K. Development and Optimization of Aceclofenac
nano particles by 32 factorial design. Int j Bio & Tox Res 2011; 1(2):108-14.
12. Noushin B, Naghmeh H, Seyed M F, Bijan S.Formulation and optimization of
Captopril sublingual tablets using D-optimal design. Iran j Pharm Res 2008;
7(4):259-67.
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Signature of the candidate
(ARUN GOKUL T.S)
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Remarks of the Guide
Krishnananda Kamath K,
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11.1 Name and Designation of the
Guide
Asst. Professor,Dept. of Quality Assurance
Srinivas college of pharmacy
11.2
Signature
11.3
Name and Designation of the
Co-Guide
11.4 Signature
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-----------
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Head of the Department
Dr. E.V.S. Subramanyam,
Professor and Head,
Dept of Quality Assurance
Srinivas college of Pharmacy
12.1 Signature
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Recommended and forwarded for
consideration.
13.1 Remarks of the Principal
13.2 Signature
Dr. A. R. SHABARAYA
Principal, Srinivas College of Pharmacy,
Valachil, Mangalore
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