FORMULATION AND EVALUATION OF IBUPROFEN TOPICAL

GEL

DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

BY

ANKATHI.ASHOK

M.PHARM, PART-1,
DEPARTMENT OF PHARMACEUTICS
T.JOHN COLLEGE OF PHARMACY
GOTTIGERE, BANNERGATTA ROAD
BANGALORE- 83, KARNATAKA.

UNDER THE GUIDANCE OF

Dr. SANDHYA K V
DEPARTMENT OF PHARMACEUTICS,
T.JOHN COLLEGE OF PHARMACY,
GOTTIGERE, BANNERGATTA ROAD,
BANGALORE- 83, KARNATAKA.
 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR PG DISSERTATION

NAME OF THE ANKATHI ASHOK,

CANDIDATE & T.JOHN COLLEGE OF PHARMACY,
ADDRESS (IN BLOCK GOTTIGERE POST,
LETTERS) BANNERGHATA ROAD,
1. BANGALORE-83,
KARNATAKA.

T.JOHN COLLEGE OF PHARMACY,

NAME OF THE GOTTIGERE POST,
INSTITUTION BANNERGHATA ROAD,
BANGLORE-83,
2.
KARNATAKA.

COURSE OF STUDY MASTER OF PHARMACY IN PHARMACEUTICS

AND SUBJECT
3.

DATE OF ADMISSION 20th September 2010

TO COURSE
4.

TITLE OF THE TOPIC “FORMULATION AND EVALUATION OF

5. IBUPROFEN TOPICAL GEL.’’
6. SIGNATURE OF THE
CANDIDATE
(Ankathi Ashok)

7. REMARKS OF THE GUIDE

RECOMMENDED FOR
DISSERTATION WORK.
8. Name & Designation of
(in block letters)

8.1 GUIDE Dr. SANDHYA KV.

DEPARTMENT OF PHARMACEUTICS,
T.JOHN COLLEGE OF PHARMACY.

8.2 SIGNATURE
(Dr. SANDHYA K V)

Name & Designation of

(in block letters)

8.3 HEAD OF THE Dr. SANDHYA K V

DEPARTMENT DEPT OF PHARMACEUTICS
T.JOHN COLLEGE OF PHARMACY

8.4 SIGNATURE (Dr. SANDHYA K V)

9.
9.1 REMARKS OF THE
PRINCIPAL FORWARDED AND RECOMMENDED FOR
FAVOURABLE COSIDERATION

9.2 SIGNATURE

(Dr. Vineeth Chandy)

10.
RESUME BRIEF OF INTENDED WORK

10.1 NEED FOR STUDY:

Topical drug delivery systems are gaining increase in popularity and several drugs have
been successfully delivered by this route for both local and systemic action. In recent years,
most of non-steroidal anti inflammatory drugs (NSAID’S) have been designed to deliver
the drugs in the form of topical gels to avoid gastrointestinal irritation, to overcome “ first
pass effect” and maximize the drug concentration at the site of action. Gels have better
potential as a vehicle to administer the drug topically in comparison to ointment because
they are non- sticky, require low energy during the formulation, stable and have aesthetic
value. Gels are transparent to opaque semi solids containing a high ratio of solvent to gelling
agent. Gels tend to be smooth, elegant, non greasy and produce non greasy effect and utilize
better drug release when compared to semi solid formulations.

Drug delivery through the skin has been a promising concept for a long time because skin is
easy to access, has a large surface area with vast exposure to the circulatory and lymphatic
networks and the route is noninvasive. Transdermal delivery is of great importance for drugs
that may cause systemic side effects such as non steroidal anti-inflammatory drugs.

Topical gel formulations provide a suitable delivery system for drugs because as they are
less greasy and can be easily removed from the skin. Percutaneous absorption of drugs from
topical formulations involves the release of the drug from the formulation and permeation
through skin to reach the target tissue. The release of the drug from topical preparations
depends on the physicochemical properties of the vehicle and the drug employed. In order
to enhance drug release and skin permeation, methods such as the selection of a suitable
vehicle, co-administration of a chemical enhancer have been studied. Gel base formulation
makes the drug molecules more easily removable from the system than cream and ointment.
Gels for dermatological use have several favorable
Properties such as being thixotropic, greaseless, easily spreadable, easily removable,
emollient, nonstaining, compatible with several excipients and water-soluble or miscible.

Ibuprofen is a propionic acid derivative and used as non-steriodal anti-inflammatory agent,

anti-pyretic, cox inhibitor, analgesic and anti-inflammatory agent. It is used for treatment of
rheumatoid arthritis, juvenile rheumatoid, osteoarthritis, to treat mild to moderate pain,
manage dysmenorrheal, to reduce fever.

ADVANTAGES OF TOPICAL DRUG DELIVERY:

1. Avoids the hepatic first pass metabolism.

2. Improves the bioavailability.
3. Decreases the dose to be administered.
4. Decreases the gastro intestinal side effects.
5. Easy to discontinue in case of toxic effects.
6. Improved patient compliance.

LIMITATIONS OF TOPICAL DRUG DELIVERY:

1. Drug with high blood concentrations cannot be administered.

2. It can be difficult for the drugs to permeate through the skin as skin acts as
Both physical and chemical barrier.
3. Drug incorporated in topical formulation should be checked for skin irritation.
4. In topical gel formulations, it may stain clothes.
5. Drug with low molecular sizes is only suitable for formulation.
6. Limited drug permeability through skin.
7. Ionic drugs cannot be delivered Transdermal.
8. Drugs cannot be delivered in pulsatile fashion.
10.2 REVIEW OF LITERATURE:

Rhee YS, Park S et al., Developed a Transdermal gel formulation for Ibuprofen using
experimental design technique to evaluate its pharmacokinetic properties. The three factors
chosen for factorial design were the concentration of drug where in the levels of each factor
were low, medium and high. Skin permeation rates and lag times of Ibuprofen were
evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The
pharmacokinetic properties of the optimized formulation were compared with those of two
marketed products in rats. It was concluded that a transdermal Ibuprofen gel could be
formulated using the technique of experimental design.1

Sang-chul et al., Has developed Lidocaine gels for enhanced local anesthetic effects. The
HPMC based bio-adhesive polymer gel containing an enhancer was formulated. Among
various enhancers studied, Diethylene glycol showed the greatest enhancing effects on drug
permeation through skin.2

Kyo-Hu Yang et al., Developed Tretinoin gels for enhanced transdermal delivery. They
studied the release characteristics of drug from carbopol gel according to temperature,
receptor medium and drug concentration. The carbopol gel of tretinoin containing an
enhancer could be developed for the enhanced transdermal delivery of drug.3

Saleem M.A et al. Had formulated and evaluated gatifloxacin topical gels. The release of
Gatifloxacin was slow and extended for longer period of time following first order kinetics.
Gatifloxacin in case of 1%w/w glycerin as humectants was found to be good as topical gel
among the prepared gels.4

Uma Devi et al., Carried out the work on tetracycline gels and evaluated for pH, drug
content, drug release, extrudability and skin irritability.5
Maly K DAS et al., Investigated that the potential gastrointestinal disorders associated with
oral administration of rofecoxib can be avoided by delivering the drug to the inflammation
site at a sustained, concentrated level over an extended period of time. Hydroxy propyl
methylcellulose (HPMC), sodium alginate and Carbopol 940 were used to develop topical
gel formulations of rofecoxib. The effects of polymer composition on the rate of drug release
from the gel formulations were examined through cellulose membrane mounting on a
Keshary-Chien diffusion cell. The effects of initial drug concentration and viscosity on the
permeation rate of rofecoxib from the gel formulations were evaluated using rat epidermis
at 37±0.5 0. The anti-inflammatory activity of the rofecoxib gel formulation was evaluated
using the rat hind paw edema model. The drug permeation rate increased with an increase of
the initial drug concentration in gels up to 25 % w/w. An inverse relationship was observed
between the in vitro drug release rate/ex vivo permeation rate and viscosity of the gel
formulations.6

Mitkari BV et al., found the formulation of liposomes for topical delivery of fluconazole
using the factorial design approach .Amount of phospholipid (PL 90H) and cholesterol (CH)
were taken at three different levels and liposoes were prepared using film hydration
technique. Gels containing liposomes were prepared in carbopol 934 NF and were
characterized for rheology, spreadability, permeation and drug deposition in the rat skin.7

Bazigha K Abdul Rasool et al., developed an ibuprofen transdermal gel with a capability
for both topical and systemic drug delivery. Ibuprofen gel formulations were prepared using
various permeation enhancers and chitosan as gelling agent .These formulations were
examined for their in vitro characteristics including viscosity, pH and drug release as well
as in vivo pharmacological activities. Ibuprofen gel preparations containing 5 % menthol
and 20 % propylene glycol exhibited pronounced analgesic activity and developed for
topical and systemic delivery of ibuprofen.8
Sujit Kumar Debnath et al., investigated to formulate topical gel containing
1.5% Aceclofenac, 1% Benzyl Alcohol, 3% Linseed oil, 10% Methyl Salicylate, 0.01%
Capsaicin, 5% Menthol and evaluate the same. Aceclofenac is a Non-Steroidal Anti-
Inflammatory Drug, used in the treatment of inflammation and degenerative disorder of the
musculoskeletal system. It is widely prescribed for the treatment of osteoarthritis,
rheumatoid arthritis, dysmenorrheal, acute lumbago, musculoskeletal trauma and gonalgia
(Knee pain). Aceclofenac is well tolerated, with most adverse events being minor and
reversible and affecting mainly the G.I system.9

Japan Patel et al., conducted study to develop a gel formulation of aceclofenac using four
types of gelling agents: carbopol, hydroxy propyl methyl cellulose (HPMC), carboxy methyl
cellulose sodium (Na CMC) and sodium alginate. Effect of penetration enhancer (propylene
glycol) on the release has been studied. The gels were evaluated for physical appearance,
rheological behavior, drug release and stability. The drug release from all gelling agents
through a standard cellophane membrane was evaluated using Keshary-Chien diffusion
cell.10

10.3 OBJECTIVES OF THE STUDY:

The present study is planned to formulate and evaluate the ibuprofen gels for topical
administration .the work will be scheduled as:

1. Evaluate the drug and the excipients for compatibility studies.

2. Formulation of topical gels.
3. Optimization of formulation parameters.
4. Physicochemical characterization of topical gels such as estimation of
drug content, viscosity determination etc..
5. Assessment of formulations for in-vitro drug release studies.
 6. Best formulation will be subjected for stability studies as per ICH guidelines.

11.

MATERIALS AND METHODS:

11.1 MATERIALS:

Drug : Ibuprofen

Polymers : Different grades of hydroxyl propyl methyl cellulose like

HPMC K4M, HPMC K100M, HPMC E50LV etc.
Carbopol, eudragit, guar gum, sodium alginate, etc.

11.2 Methods:

The following methods are used for preparation of topical gels:

1. Hot/cold technique
2. Solvent diffusion and evaporation method.
3. Hydro dynamically balanced systems
4. Low density system etc..

Evaluation of gels is carried out for:

(a)Clarity
(b) pH measurement
(c)Homogenicity
(d)Spreadability
(e)Viscosity study
(f) Drug content
(g) Skin irritation test
(h) Anti-inflammatory study
(i) Drug diffusion studies
 (j) In vivo studies
(k) Stability studies.

11.3 source of data

1. Library and e-journals.

2. Journals and books

11.4 Method of collection of data

1. Laboratory studies which include preformulation studies, formulation and evaluation

studies such as drug released rate kinetics & stability studies etc..

2. Data of physicochemical properties of the drug and polymers used such as solubility
in various solvents, pH will be collected through literature search.

11.5. Does the study require any investigation or intervention to be conducted on patients
or other humans or animals? If so, please mention briefly.

-NO-
11.6. Has ethical clearance been obtained from your institution in case of 11.5 ?

-NOT APPLICABLE-
12. LIST OF REFERENCES:-

1. Rhee YS, Chang S, Park E. Optimization of Ibuprofen gel formulation using experimental
design technique for enhanced transdermal penetration. Int J Pharm 2008;364:14-20.
2. Sang chul, Chrong-Weon cho, Yo-O Yang. Development of lidocaine gels for enhanced
local anaesthetic action. International journal of pharmaceutics 2004; 287:73-78.
3. Sang chu shin, Hee-Jung kim, In: Joon oh, Cheong-Weon cho and Kyu-Ho
Yang.Development of tretinoin gels for enhanced transdermal delivery. European Journal
of pharmaceutics and Biopharmaceutics 2005; 690:67-71.
4. Saleem MT, Sanaullah , Faizan S. Formulation and Evaluation of Gatifloxacin topical
gels. The Indian pharmacist 2006; 7:88-92.
5. Uma devi S, Ganesan M, Mahanta GP, Manavalan R. Design and Evaluation of
tetracycline HCl gels. Indian Drugs 2002;39(10):552-554.
6. Malay K. Das and Abdul B Ahmed. Formulation and ex vivo evaluation of rofecoxib gel
for topical application. Acta Poloniae Pharmaceutical and Drug Research 2007; Vol. 63:
461-467.
7. Mitkari BV, Korde SA, Mahadik KR, Kokare CR. Formulation and Evaluation of Topical
Liposomal Gel for Fluconazole. Indian J Pharm Educ Res Oct – Dec 2010:55-58.
8. Bazigha K Abdul Rasool1, Eman F Abu-Gharbieh, Sahar A Fahmy, Heyam S Saad and
Saeed A Khan. Development and Evaluation of Ibuprofen Transdermal Gel Formulations.
Tropical Journal of Pharmaceutical Research August 2010; 9 (4): 355-363.
9. Sujit KumarDe nath, Sibaji Sarkar K, Janakiraman , Sumit Chakraborty. Formulation and
Evaluation of Aceclofenac Gel. International Journal of ChemTech Research Vol.1;
No.2:204-207.
10. Japan Patel, Brijesh Patel, Hardeep Singh banwait, Kaushal parmar, Manish patel.
Formulation And Evaluation of Topical Aceclofenac Gel Using Different Gelling Agent.
International Journal of Drug Development & Research Jan-March 2011; Vol 3: 0975-9344.