A Project report

On

TITLE

Submitted in partial fulfilment for the

Academic requirement in degree of
BACHELOR IN PHARMACY

By
Name (Roll No. )

B Pharm 4th Year

Under the Guidance of

Name of Faculty
Designation

RAM-EESH INSTITUTE OF VOCATIONAL & TECHNICAL EDUCATION

Knowledge Park I, Greater Noida, Uttar Pradesh 201310
from
Dr. A.P.J. ABDUL KALAM TECHNICAL UNIVERSITY
LUCKNOW, INDIA
2021-2022
 CERTIFICATE

This is certify that the work contained in this project, entitled “ --------------

” submitted in partial fulfilment for the academic requirement in the degree of

Bachelor of Pharmacy is the original work carried out during the academic year

2021-2022 by __________ (Roll No.________), _________________(Roll No. )

under our supervision and guidance.

Forwarded By
Principal

Date:
 DECLARATION
We hereby declare that the work entitled, “
” embodied in the project was carried out by us during the academic
session 2021-2022 under the supervision and guidance of
__________________________
We further declare that no part of this project has been submitted either
in part or in full for any other degree Dr. A. P. J. Abdul Kalam
Technical University, Uttar Pradesh, Lucknow.
Students Names

Date:
Place:
 Certificate
This is to certify that the Project entitled……………..………………………………………

……………………………..……………………………………………………….........................

by..………………………………… Enrollment No………………………………has been

prepared by me without resorting to Plagiarism. I shall be held responsible for any

issues related to Plagiarism as per the UGC (Promotion of academic integrity and

prevention of plagiarism in higher education institutions) regulations, 2017.

Signature of the Student

Name of the students

 TABLE OF CONTENTS

S NO. CONTENTS PAGE NO.

1. Introduction
2. Literature Review
3. Aim and Objective
4. Formulation Procedure
5. Materials used
6. Preparation
7. Evaluation
8. Result and Discussion
9. Conclusion
10 References
Transdermal use of Ibuprofen - An Analysis 
 Introduction: 
The Development of Transdermal gels has been a pathbreaking development
in the medical field. The simplification and rise in efficacy that this
development has brought to the pharmaceutical industry are close to
infinity. 

 What is Transdermal?
TRANSDERMAL Gels are semisolid systems in which a liquid phase is
constrained within a three-dimensional polymeric matrix of natural or
synthetic gums in which a high degree of physical or chemical cross-
linking has been established. 
In simple words, A transdermal gel is a local medication that is applied to
and absorbed directly through the skin.

Transdermal drug delivery systems are gaining popularity, as several

drugs have been successfully delivered by this route. Drug delivery
through the skin has been a promising concept for a long time because
the skin is easy to access, has a large surface area with vast exposure to
the circulatory and lymphatic networks and the route is noninvasive. [1]
(tropical journal). Transdermal delivery is important for drugs that may
cause systemic side effects such as non-steroidal anti-inflammatory drugs
(NSAIDs).

 History of transdermal medication.

For thousands of years, people have placed substances on
the skin for therapeutic effects. In the modern era, a variety
of topical formulations have been developed to treat local
indications. The first transdermal system for systemic
delivery—a three-day patch that delivers scopolamine to
treat motion sickness—was approved for use in the United
States in 1979. A decade later, nicotine patches became the
first transdermal blockbuster, raising the profile of
transdermal delivery in medicine and for the public in
 general. Today, there are 19 transdermal delivery systems
for such drugs as estradiol, fentanyl, lidocaine and
testosterone; combination patches containing more than
one drug for contraception and hormone replacement; and
iontophoretic and ultrasonic delivery systems for analgesia
(Table 1,). Between 1979 and 2002, a new patch was
approved on average every 2.2 years. Over the past 5 years
(2003–2007), that rate has more than tripled to a new
transdermal delivery system every 7.5 months. It is
estimated that more than one billion transdermal patches
are currently manufactured each year.

Table 1
Transdermal drugs approved by the US FDA.

Approva Drug Indication Product Marketing

l year Name company

1979 Scopolamine Motion Transderm- Novartis

sickness Scop Consumer Health
(Parsippany, NJ)

1981 Nitroglycerin Angina Transderm- Novartis (East

pectoris Nitro Hannover, NJ)

1984 Clonidine Hypertension Catapres- Boehringer

TTS Ingelheim
(Ridgefield, CT)

1986 Estradiol Menopausal Estraderm Novartis (East

symptoms Hannover, NJ)
1990 Fentanyl Chronic pain Duragesic Janssen
Pharmaceutica
(Titusville, NJ)

1991 nicotine Smoking Nicoderm, GlaxoSmithKline

cessation Habitrol, (Philadelphia,
ProStep PA), Novartis
Consumer Health
(Parsippany, NJ)
Elan
(Gainesville, GA)

1993 Testosterone Testosterone Testoderm Alza, Mountain

deficiency View, CA

1995 Lidocaine/epinephrine Local dermal Iontocaine Iomed (Salt Lake

(iontophoresis) analgesia City, UT)

1998 Estradiol/norethidrone Menopausal Combipatch Novartis (East

symptoms Hannover, NJ)

1999 Lidocaine Post-herpetic Lidoderm Endo

neuralgia Pharmaceuticals
pain (Chadds Ford,
PA)

2001 Ethinyl Contraception Ortho Evra Ortho-McNeil

estradiol/norelgestromi Pharmaceutical
n (Raritan, NJ)
2003 Estradiol/levonorgestrel Menopausal Climara Bayer Healthcare
symptoms Pro Pharmaceuticals
(Wayne, NJ)

2003 Oxybutynin Overactive Oxytrol Watson Pharma

bladder (Corona, CA)

2004 Lidocaine (ultrasound) Local dermal SonoPrep Echo

anesthesia Therapeutics
(Franklin, MA)

2005 Lidocaine/tetracaine Local dermal Synera Endo

analgesia Pharmaceuticals
(Chadds Ford,
PA)

2006 Fentanyl HCl Acute Ionsys Alza, Mountain

(iontophoresis) postoperative View, CA
pain

2006 Methylphenidate Attention Daytrana Shire (Wayne,

deficit PA)
hyperactivity
disorder

2006 Selegiline Major Emsam Bristol-Myers

depressive Squibb
disorder (Princeton, NJ)
 2007 Rotigotine Parkinson’s Neupro Schwarz Pharma
disease (Mequon, WI)

2007 Rivastigmine Dementia Exelon Novartis (East

Hannover, NJ)

*Thislist includes transdermal patches and delivery systems approved by the FDA. Only the first
approved product for a given drug or drug combination administered by a given delivery
method is shown. Topical creams, ointments, gels and sprays are not included.

 Advantages
Transdermal delivery has a variety of advantages compared with the oral
route. In particular, it is used when there is a significant first-pass effect of
the liver that can prematurely metabolize drugs. Transdermal delivery also
has advantages over hypodermic injections, which are painful, generate
dangerous medical waste and pose the risk of disease transmission by needle
re-use, especially in developing countries. In addition, transdermal systems
are non-invasive and can be self-administered. They can provide release for
long periods of time (up to one week). They also improve patient
compliance and the systems are generally inexpensive.
Another area of great interest is the delivery of vaccines. In addition to
avoiding hypodermic needles, transdermal vaccine delivery could improve
immune responses by targeting delivery to immunogenic Langerhans cells
in the skin. Given the external placement and patient control over patches, it
might also be possible to develop modulated or pulsatile delivery, which
could involve feedback control. Indeed, an analgesic patch was recently
approved in the United States that uses patient-regulated delivery of fentanyl
modulated by electricity to control pain (iontophoresis), which has also been
launched in Europe.
Finally, there is the possibility of not only delivering drugs, but also
extracting molecules (analytes) through the skin. This has already been
achieved for glucose monitoring by extracting interstitial fluid using
electrical means and is in clinical trials using other approaches, such as
ultrasound.
From a global perspective, it can be said that advances in transdermal
delivery systems can be categorized as undergoing three generations of
 development from the first generation of systems that produced many of
today’s patches by judicious selection of drugs that can cross the skin at
therapeutic rates with little or no enhancement; through the second
generation that has yielded additional advances for small molecule delivery
by increasing skin permeability and driving forces for transdermal transport;
to the third generation that will enable transdermal delivery of small
molecule drugs, macromolecules (including proteins and DNA) and virus-
based/other vaccines through targeted permeabilization of the skin’s stratum
corneum.

IBUPROFEN

 Ibuprofen:
Ibuprofen was the first member of Propionic acid derivatives introduced in
1969. It is a popular domestic and over the counter analgesic and antipyretic
for adults and children. Ibuprofen has been rated as the safest conventional
NSAID by spontaneous adverse drug reaction reporting systems in the UK.
Ibuprofen is (2RS)-1[4-(2-methyl propyl) phenyl] propionic acid (BP.
2004). Ibuprofen was the first member of propionic acid derivatives to be
introduced in 1969 as a better alternative to Aspirin. Gastric discomfort,
nausea and vomiting, though less than aspirin or indomethacin, are still the
most common side effects.

Ibuprofen is the most commonly used and most frequently prescribed

NSAID. It is a non-selective inhibitor of cyclo-oxygenase-1 (COX-1) and
Cyclooxygenase-2 (COX-2). Although its anti-inflammatory properties may
be weaker than those of some other NSAIDs, it has a prominent analgesic
and antipyretic role. Its effects are due to the inhibitory actions on cyclo-
oxygenases, which are involved in the synthesis of prostaglandins.
Prostaglandins have an important role in the production of pain,
inflammation and fever.

Administration:

Administration of a drug is of prime importance while analyzing its efficacy.

The more effective the administration of a drug the more effective its result.
Administration of an Ibuprofen can be of four modes, they are:
a. Mouth
b. Rectal
c. Topical
d. Intravenous
This report focuses on Topical or Transdermal administration of Ibuprofen.
This is generally done through the use of Ibuprofen gel.

Ibuprofen gel:

Ibuprofen is a medication in the nonsteroidal anti-inflammatory drug class

that is used for treating pain, fever, and inflammation. This includes painful
menstrual periods, migraines, and rheumatoid arthritis. It may also be used
 to close a patent ductus arteriosus in a premature baby. When this Ibuprofen
is preferred in the form of a gel it is referred to as Ibuprofen gel.
Ibuprofen gel is a topical analgesic and anti-inflammatory gel to relieve pain
and inflammation in your body. It is most commonly used for the relief of
 Rheumatic pain (pain caused by problems with muscles, tendons, joints
or bones)
 Muscular aches and pains
 Pains from strains and sprains
 Backache
 Lumbago (lower back pain)
 Fibrositis (muscle tenderness or stiffness)

Ibuprofen gel is applied directly to the skin on the area where you are
experiencing pain or inflammation and is absorbed through the skin to
reduce inflammation at the point of pain.
It works by reducing hormones that cause pain and swelling in the body.
It’s a clear, non-greasy gel with no fragrance, and is extremely effective for
quick relief of pain, muscular aches, swellings, backache and sports
injuries.
 Aim/ Objective:
The objective is to prepare a transdermal topical gel of Ibuprofen using
Carbopol which can be effectively used for transdermal topical delivery.
This is also to Analyze and bring out a scientific understanding of the
formulation and efficacy of Ibuprofen topical gel through empirical
experimentation.

Formulation or procedure of making:

 The making of the gel is an elaborate, delicate and diligent process. It is
necessary to remember to ensure that no ingredients are used that may
cause irritation and damage to the skin, this is owing to its feature of being
a transdermal drug. The one preparing the drug must ensure that there is no
default with the preparation of the drug. It is preferable to use aluminium-
based packing due to its high malleability and leakage proof nature. High
care must be taken with refrigeration and storage of the materials and the
gel as required at different stages of preparation.

 Materials used :
Chemical Components:
a. Carbopol 
b. Methyl Paraben
c. Triethanolamine 
d. Glycerol
e. Ibuprofen.
Apparatus:
a. Beaker
b. Magnetic Stirrer
c. Glass rod 
d. Beads
e. Conical Flask
f. U.V Spectroscope

  Preparation:
 Preparation of transdermal gel: 
Gels were prepared by dispersing the polymers (Carbopol) in a mixture of
water and glycerol with methylparaben as the preservative and the
varying amount of ibuprofen, being kept under magnetic stirring until the
homogeneous dispersion was formed. The dispersion was then neutralized
and made viscous by the addition of triethanolamine [8,9] as shown in
Table 2.
Table 2

Formulatio   Drug Carbopol Methyl Glycerol Triethanolamine

n    (mg)     (gm) Paraben    (ml)          (ml)
     Code        (mg)
      F1     0.1         0.1

      F2     0.1         0.1

      F3     0.1         0.1

      F4     0.1         0.1

      F5     0.1         0.1

Preparation of Standard Curve:

0.1mg of ibuprofen was weighed accurately and was dissolved in 10 ml of
ethanol and the volume was adjusted to 100 ml by pH 7.4 and various
dilutions were made to obtain concentration 2-50 mcg/ml and the
absorbance was measured in the Ultra Violet (UV) Spectrophotometer at
λmax 267 nm, and a standard curve was obtained by plotting
concentration against the absorbance.
 
Preparation of pH 7.4
1.19 gm of Disodium Hydrogen Phosphate, 0.095 gm of Potassium
Dihydrogen Phosphate and 4 gm of Sodium Chloride were weighed
accurately and it was diluted up to 500 ml.
 
Evaluation Of Transdermal Gel:
Determination of gel pH 
The pH of the three gel formulations was determined by using digital pH
meter after calibration with standard buffer pH 4.0, and 9.0 by inserting
the electrode system into the gel.
Spreadability 

 
One of the criteria for a gel to meet the ideal quantities is that it should
possess good spreadability. It is the term expressed to denote the extent of
the area to which gel readily spreads on application to the skin or affected
part. The therapeutic efficacy of a formulation also depends upon its
spreading value. Spreadability is expressed in terms of time in seconds
taken by two slides to slip off from the gel and placed in between the
slides under the direction of certain load. Lesser the time is taken for
separation of two slides, better the spreadability. It is calculated by using
the formula: S = M. L / T Where M = weight tied to upper slide, L =
length of the glass slide, T = time taken to separate the slides.
 
 
 
Viscosity 
Brookfield (DV-E Viscometer) attached with  spindle was used for
determination of viscosity. Gels were filled in the jar and the spindle was
lowered perpendicularly taking care that the spindle does not touch the
 bottom of the jar. The spindle was rotated in the gel at 158 rpm. At each
speed, the corresponding dial reading was noted. The reverse reading was
also noted and the average was taken for these two readings. The viscosity
of the gel was obtained by the multiplication of the dial readings with the
factors given in the Brookfield viscometer catalogues.
The drug content  of 1 gm of the prepared gel was weighed accurately and
dissolved in 10 ml of ethanol and was then filtered.1ml of the filtrate was
taken and was diluted up to 100 ml by pH 7.4 and was observed in the
Ultraviolet (UV) spectrophotometer at 267 nm.
 

RESULT AND DISCUSSION 

Standard calibration curve of Ibuprofen: 
The standard calibration curve of Ibuprofen was plotted in phosphate
buffer, pH 7.4. The scanning of the standard solution has resulted in
maximum absorption peak at the wavelength of 267 nm. It was observed
that Beer-Lambert‘s law was obeyed within the concentration range of 2.0
μg/ml to 100 μg/ml, in phosphate buffer, pH 7.4 as shown in Fig. 1.
Fig.1
 Drug spreadability study: 
The spreadability of the different gel formulations after 1 min. was
determined and was compared with a standard gel and noted in Table 3. 
 
 
 

Table 3: Spreadability of Gel Formulation

Formulation Spreadability (mean+SD)

    F1           14.07
    F2           18.08
    F3           23.19
    F4           19.07
    F5           24.57
    

 
Viscosity: 
The viscosity of the gel formulations was found between 158 Pa/s
 
 
 
 
Wavelength:
 
 Preformulation Studies:

Drug-Excipient compatibility Studies: Drug is the active part of dosage

forms and  it is mainly responsible for the therapeutic value and excipients
substance which are included along with drugs formulated in a dosage
form so as impart specific qualities to them. It is important for determining
of stability of the dosage. It is also used for the development of new drug
delivery systems as well as the investigation of new drugs.
 

 DISCUSSION
The Carbopol gels of Ibuprofen were found to be homogenous with good
drug loading. The pH of all the gel formulations was found within the
neutral pH range which is compatible with skin. And the viscosity of all
formulations was found to be feasible for topical drug delivery. The drug
content of the three formulations was found in the range of 87.56 to
90.45% which shows efficient drug loading. Results of in-vitro drug
release study showed that F5 formulation has better diffusion of drug
through egg membrane and hence further permeation studies were carried
out through rat epidermis. The compatibility study showed that the major
peaks in Fourier- transform infrared spectroscopy (FTIR) spectra of the
pure drug were found to be intact in their physical mixture. Hence there is
no interaction between drug and Carbopol in their physical mixture.
 
 
 CONCLUSION
It can be concluded that Carbopol can be effectively used as the polymer
for topical gel preparation. And F5 formulation containing 0.5 % w/w
Carbopol 940 may be effectively used as topical transdermal delivery for
Ibuprofen.
                                    
 REFERENCES
1.  Miller MA, Pisani E. The cost of unsafe injections. Bull World Health
Organ. 1999;77:808–811. [PMC free article] [PubMed] [Google
Scholar]
2.  Foldvari M, Babiuk S, Badea I. DNA delivery for vaccination and
therapeutics through the skin. Curr Drug Deliv. 2006;3:17–28.
[PubMed] [Google Scholar]
3. Glenn GM, Kenney RT. Mass vaccination: solutions in the skin. Curr
Top Microbiol Immunol. 2006;304:247–268. [PubMed] [Google
Scholar]
4. Mayes S, Ferrone M. Fentanyl HCl patient-controlled iontophoretic
transdermal system for the management of acute postoperative pain.
Ann Pharmacother. 2006;40:2178–2186. [PubMed] [Google Scholar]
5. Sieg A, Guy RH, Delgado-Charro MB. Noninvasive and minimally
invasive methods for transdermal glucose monitoring. Diabetes
Technol Ther. 2005;7:174–197. [PubMed] [Google Scholar]
6. Rabia Bushra* and Nousheen Aslam. An Overview of Clinical
Pharmacology of Ibuprofen. https://www.ncbi.nlm.nih.gov/pubmed/?
term=Bushra%20R%5BAuthor
%5D&cauthor=true&cauthor_uid=22043330
7. Tripathi KD. Non steroidal anti inflammatory drugs and anti pyretic
analgesics. In: Essentials of medical pharmacology. 5th edn., Jaypee
Brothers, New Delhi, 2003. p. 176. [Google Scholar]
8. Abrahm P. KI KD. Nitro-argenine methyl ester, a non selective
inhibitor of nitric oxide synthase reduces ibuprofen-induced gastric
mucosal injury in the rat. Dig Dis 2005;50(9):1632-1640
.10.1007/s10620-005-2908-y [PubMed] [CrossRef] [Google Scholar]
9. Bradbury F. How important is the role of the physician in the correct
use of a drug? An observational cohort study in general practice. Int J
Clin Prat 2004; (144):27-32. [PubMed]
10. Chavez ML, DeKorte CJ. Valdecoxib: a review. Clin Ther 2003.
Mar;25(3):817-851. 10.1016/S0149-2918(03)80110-8 [PubMed]
[CrossRef] [Google Scholar]
11. Wahbi AA, Hassan E, Hamdy D, Khamis E, Barary M.
Spectrophotometric methods for the determination of Ibuprofen in
tablets. Pak J Pharm Sci 2005. Oct;18(4):1-6. [PubMed] [Google
Scholar]
12. Ritter JM, Lewis L, Mant TG. Analgesics and the control of pain. In:
A text book of clinical pharmacology. 4th ed., Arnold London, 1999. p.
216. [Google Scholar]
13. Herzfeld CD, Kummel R. Dissociation constant, solubilities and
dissolution rate of some selective non steroidal anti inflammatory
drugs. Drug Dev Ind Pharm 1983;9(5):767-793. [Google Scholar]
14. Ross JM, DeHoratius J. Non narcotic analgesics. In: DiPalma JR and
DiGregorio GJ editors. Basic pharmacology in medicine. 3rd ed.,
McGraw hill publishing company New York, 1990. p. 311-316. [Google
Scholar]
15. Antal EJ, Wright CE, III, Brown BL, Albert KS, Aman LC, Levin
NW. The influence of hemodialysis on the pharmacokinetics of
ibuprofen and its major metabolites. J Clin Pharmacol 1986.
Mar;26(3):184-190. [PubMed] [Google Scholar]
16. Katzung BG, Furst DE. Non steroidal anti inflammatory drugs, disease
miodifying anti rheumatic drugs, non opioid analgesics, drugs used in
gout. In: Katzung BG editor. Basic and clinical pharmacology, 7th ed.,
Appliton and Lang Stamford, Connecticut, 1998. p.586, 1068. [Google
Scholar]
17. Olive G. Analgesic/Antipyretic treatment: ibuprofen or
acetaminophen? An update. Therapie 2006. Mar-Apr;61(2):151-160.
10.2515/therapie:2006034 [PubMed] [CrossRef] [Google Scholar]
18. Compreton EL, Glass RC, Hird ID. The pharmacokinetic of ibuprofen
in elderly and young subjects. 1984 Boots research reports DT 84041.
19. Senekjian HO, Lee C, Kuo TH, Krothapalli R. An absorption and
disposition of ibuprofen in hemodialysed uremic patients. Eur J
Rheumatism and inflammation 1983; 6(2):155-162. [PubMed]
20. Physician’s desk reference. 51st ed., Published by Medical Economic
Company, Inc. at Montvale, 1997. p. 1389-1391. [Google Scholar]
21. Moore N. Forty years of ibuprofen use. Int J Clin Pract Suppl 2003.
Apr;(135):28-31. [PubMed] [Google Scholar]
22. Kashyap Ankita*, Das Asha , Ahmed Abdul Baquee. Formulation and
Evaluation of Transdermal Topical Gel of Ibuprofen.
http://jddtonline.info
23. Mark R. Prausnitz1 and Robert Langer2 .Transdermal drug delivery
https://www.ncbi.nlm.nih.gov/pubmed/?term=Prausnitz%20MR
%5BAuthor%5D&cauthor=true&cauthor_uid=18997767