Rao et al Journal of Drug Delivery & Therapeutics. 2019; 9(2):197-205
ISSN: 2250-1177 [197] CODEN (USA): JDDTAO
Available online on 15.03.2019 at http://jddtonline.info
Journal of Drug Delivery and Therapeutics
Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted
non-commercial use, provided the original work is properly cited
Open Access Research Article
Design of transdermal patch of ketoprofen by full factorial design for
treatment of rheumatoid arthritis
Rao Monica*, Sonavne Vijay, Kulkarni Sayali, Magar Mayuri, Zope Abhishek, Karanjkar Pooja
Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune-411001
ABSTRACT
Oral therapy of NSAIDs for treatment of rheumatoid arthritis causes gastric irritation and ulceration. In the present study transdermal patch of
ketoprofen was developed using hydroxyl propyl methyl cellulose E5 and Eudragit S100. Patches were prepared by solvent evaporation method.
Optimization was carried out by 3
2
factorial design with polymer concentration (HPMC E5) and plasticizer concentration (propylene glycol) as
independent variables. Patches were evaluated for folding endurance, surface pH, drug content, percent moisture content, water uptake and
swelling studies. Ex vivo permeation studies of optimized patch was performed using Franz diffusion cell while bioadhesion force and tensile
strength were measured by using texture analyzer. Hydrophilic nature, swelling ability and wettability of polymer and plasticizer were
responsible for increase in flux and bioadhesion with increase in their concentrations in the factorial batches. Swelling index of all formulations
was in the range of 17.3 ±1.2 to 65.29 ±4.78 up to 3h. Flux obtained from all batches was in the range of 3.37±0.23 to 5.43±0.13µg/h/cm
2
. Anti-
inflammatory studies using carrageenan-induced rat paw edema showed greater paw swelling reduction in case of ketoprofen patch. Cumulative
percent drug permeation of optimized patch through nylon 66, Wistar rat skin and cadaver skin was found to be 92.3% >86.28 %>63.42% in 8h,
while flux order was 6.073> 5.442 > 2.219 µg/h/cm
2
respectively. The study concludes that transdermal patch of ketoprofen will be more
efficacious with absence of gastric irritation observed in oral formulations.
Keywords: Ketoprofen, Bioadhesion, HPMC E5, Flux, Backing membrane
Article Info: Received 05 Feb 2019; Review Completed 07 March 2019; Accepted 09 March 2019; Available online 15 March 2019
Cite this article as:
Rao M, Sonavne V, Kulkarni S, Magar M, Zope A, Karanjkar P, Design of transdermal patch of ketoprofen by full factorial
design for treatment of rheumatoid arthritis, Journal of Drug Delivery and Therapeutics. 2019; 9(2):197-205
http://dx.doi.org/10.22270/jddt.v9i2.2549
*Address for Correspondence:
Dr. Monica RP Rao, Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune-411001
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic, progressive
inflammatory disease of the joints characterized by synovial
proliferation and inflammatory and immunological
processes. These mechanisms lead to irreversible
degradative and erosive changes in the articular cartilage
and juxta articular bone. RA affects multiple joints, most
commonly small joints of the hands, feet and cervical spine,
but larger joints like the shoulder and knee can also be
involved
1,2
.
Non-Steroidal Anti-Inflammatory Drug (NSAID) and steroids
are used to reduce inflammation thereby decreasing pain
and improving function. Disease-Modifying Antirheumatic
Drugs (DMARDs) are required to inhibit the underlying
immune process and prevent long-term damage
1,3
. NSAIDS
lead to gastrointestinal side effects such as dyspepsia to
gastric bleeding
4
. The acidic character of NSAIDS may lead to
local irritation, and lesions on the gastrointestinal mucosa
are known as NSAIDS gastropathy
5
.
Ketoprofen (KTF) is a propionic acid derivative which causes
inhibition of Cyclooxygenase-2 (COX-2), an enzyme involved
in prostaglandin synthesis via the arachidonic acid pathway.
This results in decreased levels of prostaglandin that
mediate pain, fever and inflammation. KTF is a non-specific
cyclooxygenase inhibitor and inhibition of COX-1 is
responsible for its side effects, such as GI upset and
ulceration
6
. Currently available marketed dosage form of
KTF are enteric coated and extended release tablets, topical
gel, liquid spray, suppositories, extended release capsules
and formulation based on transfer some technology for
direct application on the skin has been developed
7
.
Transdermal therapeutic systems are defined as, discrete
dosage forms which, applied to the intact skin, deliver the
drugs at a controlled rate to the systemic circulation via skin
and this delivery system offers an advantageous alternative
to conventional delivery system such as injections or oral
delivery
8,9
. Transdermal drug delivery system (TDDS) offers
many advantages such as reduced side effects, less frequent
administration to produce the desired constant plasma
concentration associated with improved patient compliance,