Topical Administration of Ibuprofen for Injured Athletes: Considerations, Formulations, and Comparison to Oral Delivery
Manoukian et al. Sports Medicine - Open
Topical Administration of Ibuprofen for Injured Athletes: Considerations, Formulations, and Comparison to Oral Delivery
Martin Anthony Christopher Manoukian 0
Christopher William Migdal 0
Amode Ravindra Tembhekar 0
Jerad Alexander Harris 0
Charles DeMesa 1
0 University of California Davis School of Medicine , 4610 X Street, Sacramento, CA , USA
1 Department of Anesthesiology and Pain Medicine, University of California Davis School of Medicine , 4610 X Street, Sacramento, CA , USA
Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs commonly used to treat both the acute and chronic injuries sustained by athletes during training and competition. In many parts of the world, NSAIDs can be purchased over-the-counter and used without any physician oversight. However, the chronic nature of overuse injuries requires NSAIDs to be taken orally for an extended period of time. As a result, they can have significant adverse effects on athletes, namely gastrointestinal (GI), renal, and cardiovascular damage. Dyspepsia and upper GI ulceration and bleeding are of great concern in chronic NSAID use, and as such oral NSAIDs are generally contraindicated in those with a history of peptic ulcers or irritable bowel disease. In the setting of chronic overuse soft tissue or joint disease, topically administered NSAIDs offer an alternate route of administration that has the potential to deliver a similar level of pain and anti-inflammatory relief while bypassing the harmful side effects associated with oral intake. Topically applied NSAIDs are able to achieve high concentrations within the targeted site of action while simultaneously keeping plasma concentrations low, offering several advantages over oral administration. One commonly used generic NSAID is ibuprofen (2-(4-isobutylphenyl)propanoic acid). First synthesized in the 1960s, ibuprofen has since become widely available as an over-the-counter pharmaceutical. In this review, we outline new and different techniques that have been used to deliver ibuprofen into diseased tissues, including supersaturations, microemulsions, gels, nanosystems, and microneedles. We also review relevant clinical trials comparing transdermally delivered ibuprofen to placebo and orally administered ibuprofen.
Ibuprofen’s diffusion and absorption characteristics
make it an optimal therapeutic for transdermal
delivery to affected tissue in injured and recovering
Topically administered ibuprofen has been shown to
be superior to placebo in the treatment of joint and
soft tissue injury.
Topically administered ibuprofen has been shown to
be equally effective to orally administered ibuprofen
in the treatment of joint and soft tissue injury and is
associated with a lower incidence of unwanted
gastrointestinal side effects.
Non-steroidal anti-inflammatory drugs (NSAIDs) are
among the most commonly prescribed drugs in the world
]. While available under many brand names and
formulations, NSAIDs share a common mechanism of action
through the inhibition of cyclooxygenase 1 and
cyclooxygenase 2 (COX2). The primary anti-inflammatory effects
of NSAIDs are rooted in the inhibition of COX2-mediated
oxygenation of arachidonic acid, a key step in the
synthesis of inflammatory prostaglandins [
]. Indications for
NSAID use include osteoarthritis (OA), soft tissue injury,
and rheumatoid disease, among others [
1, 2, 5–7
indications are of particular concern for athletes,
especially elite athletes, who suffer higher rates of soft tissue
injury than non-athletes and are at a greater risk of
developing OA [
]. For the injured athlete, studies have
indicated that NSAID therapy can increase the rate of
muscle recovery via modulation of the inflammatory
response to muscle injury [
]. In addition to attenuating
the inflammatory response, the analgesic effect of
NSAIDs may assist in pain management in the
recovering athlete, allowing for increased tolerance of
rehabilitation exercises [
]. This can reduce potentially
detrimental consequences of muscle deconditioning
secondary to immobilization [
Although NSAIDs have demonstrated many
therapeutic benefits and have a strong safety profile allowing
for over-the-counter availability in the USA, they are not
without adverse effects. Of those treated with chronic
oral NSAID therapy, 90% are at risk of adverse
gastrointestinal (GI) effects, with the annual incidence of
upper GI ulcers ranging from 2 to 4% [
Furthermore, patients treated with oral NSAIDs have been
shown to have an elevated risk of cardiovascular events
and increased incidence of heart failure . Two
studies by Lanas et al. concluded that of patients treated with
oral NSAIDs for OA, 90% were at risk for GI adverse
effects and 44.3% were at risk for adverse cardiovascular
]. In addition, NSAIDs have been shown to
reduce the cardiovascular protective benefits of low-dose
aspirin when taken simultaneously [
Furthermore, renal toxicity is also a concern in patients who
use NSAIDs [
]. Altogether, the use of NSAIDs has
been estimated account for 107,000 hospitalizations and
16,500 deaths annually in the USA alone [
Studies of the adverse effects of NSAID therapy have
primarily focused on oral NSAIDs, with the increased
risk of adverse effects resulting from high plasma
concentrations. To avoid such adverse side effects, studies
have looked at both modifications of drug action and
alternative methods of drug delivery. Celecoxib was
introduced as a COX2 selective inhibitor that avoided the
adverse GI side effects of oral non-selective NSAIDs
]. However, a risk of cardiovascular events was found
to be equivalent to that of traditional NSAIDs [
Other attempts have been made to alter the chemical
structure of ibuprofen to orally deliver the same desired
therapeutic effects without the undesired ulcerogenic
]. Perhaps most promising, studies have
suggested that topical application of NSAIDs via gels,
creams, sprays, or plasters are as effective as oral
NSAIDs and yet are associated with fewer adverse side
]. This review focuses on the topical
delivery of ibuprofen, 2-(4-isobutylphenyl)propanoic acid, a
widely used NSAID. Topical ibuprofen’s effectiveness at
treating chronic musculoskeletal pain is comparable to
other topical agents such as diclofenac and ketoprofen
. However, no overview of the current state of
research in topical ibuprofen is currently available. In this
article, we will highlight the key technical aspects of
transdermal pharmaceutical delivery, review research in
novel formulations used as delivery vehicles, compare
the efficacy of topical ibuprofen against placebo and oral
ibuprofen, and touch upon the costs associated with
topical ibuprofen administration for the injured athlete.
The skin is made up of two functional layers, the
epidermis and the dermis (Fig. 1). The role of the epidermis is to
protect the body from foreign materials and mechanical
trauma as well as prevent loss of water. The superficial
layer of the epidermis is the stratum corneum, a
10–20μm thick layer of terminally differentiated keratinocytes
known as corneocytes. In addition to being covered by a
lipid film, the stratum corneum also has numerous
intercellular lipids consisting of ceramids, cholesterol, and
saturated free fatty acids [
]. Due to this intensely lipid-rich
character, the stratum corneum is largely impermeable to
hydrophilic substances, posing a hurdle to any drug that is
to be delivered topically. Below the stratum corneum sits
the remainder of the epidermis, which is devoid of
vasculature, and instead receives all of its nutrients via diffusion
from the dermis.
Below the epidermis sits the dermal-epidermal
junction, also known as the basement membrane zone. Made
up of hemidesmosomes, laminins, collagens, and
glycoproteins, the basement membrane zone’s main function
Fig. 1 Hematoxylin and eosin staining of human skin, illustrating the
layers of the stratum corneum, epidermis, and dermis. Image provided
by author MACM
is to keep the epidermis attached to the dermis and
withstand external shearing forces. Like the glomerular
basement membrane, the dermo-epidermal basement
membrane is charged, imparting selectivity to diffusion.
However, the charge of the dermo-epidermal basement
membrane is far less than that found in the glomerulus
]. Thus, although it does impart some selectivity
to absorption, the dermo-epidermal basement
membrane is much more permeable to charged molecules
than the glomerular basement membrane.
The deepest layer of the skin is the collagenous
dermis. Made up mostly of type I collagen, the dermis
serves to add pliability and flexibility to the skin, while
also serving an important role in thermoregulation of
the body and housing the various skin appendages.
These appendages, which include hair, sebaceous glands,
and eccrine and apocrine sweat glands, can serve as
conduits of drug delivery and absorption into the dermis
]. Importantly, and in contrast to the epidermis, the
dermis is heavily vascularized [
]. Thus, any drug that
diffuses into the dermis may diffuse into blood vessels to
be transported downstream and eventually reach
systemic circulation. This must be taken into account with
drugs that are potentially toxic if they are carried to
parts of the body other than their intended sites of
Traversing the Skin Barrier
Two routes of topical transdermal delivery include
traveling through the epidermis itself or, alternatively, through
the skin appendages. Because of their large size, skin
appendages allow for the absorption of larger molecules and
are much less selective [
]. However, disadvantages of
this approach include excessive sebum within the follicle,
sequestration of drug within the follicle, and lack of
appendages in some areas of the body [
transepidermal routes must also be considered.
Direct delivery of drugs through the epidermis is
complicated by its intensely lipophilic character. While this
is important in preventing water from escaping the body,
it also makes transdermal delivery of hydrophilic drugs
nearly impossible. An often cited rule is the Rule of 5
proposed by Lipinski et al. which states that non-oral
delivery of drugs can only be accomplished if the drug has
a molecular weight below 500 Da, has less than five
Hbond donors, has less than ten H-bond acceptors, and
has an octanol-water partition coefficient (also known as
log P, which is a measure of lipophilicity) below five [
Furthermore, a follow-up paper by Choy and Prausnitz
suggests that transdermal drug delivery is especially
difficult when compared to drugs crossing the ophthalmic
or pulmonary epithelium [
]. This must be taken into
consideration when preparing a vehicle with which to
deliver ibuprofen. However, the physical characteristics
of ibuprofen all fall well within Lipinski’s criteria,
favoring its use in transdermal delivery systems (Table 1)
]. This allows ibuprofen to efficiently diffuse through
the epidermal and dermal layers into the soft tissue and
connective tissue at its point of action in a way equal or
even superior to orally administered ibuprofen [
It should be noted, however, that there are many
factors specific to the athlete that can cause variation in the
transdermal diffusion and delivery of therapeutics. Sex,
age, ethnicity, skin hydration, skin temperature, obesity,
disease state, and anatomical site of application all play a
role in determining the diffusion rate of therapeutics
through the skin [
]. Application to sites with a
thick epidermis, such as the palms or soles of the feet,
for example, makes it more difficult for drugs to
penetrate than the skin of the arm or trunk.
Into the Synovium
For more efficient relief of joint swelling and pain in
intra-articular disease, transdermally delivered ibuprofen
must penetrate into the synovium. All joints in the body
are composed of a fibrous outer capsule that connects
the articulating bones involved. Within this outer
capsule lies the inner synovial membrane which is filled
with synovial fluid. This fluid utilizes hyaluronic acid
and lubricin to protect the joint from damage inducing
friction. Over time, repeated stress and injury to the
joints leads to a breakdown of the synovial capsule and
articular cartilage. This then leads to the increased
production of pro-inflammatory cytokines, synovitis,
chondritis, and pain [
]. To be effective, transdermally
delivered ibuprofen must be able to diffuse into the
synovium itself to counteract the inflammation and
provide the patient with symptomatic relief.
To get into the synovial joints, transdermally delivered
ibuprofen must either diffuse directly through the
articular capsule, or it must first diffuse into the capillaries of
the dermal papillae and then be carried by the
bloodstream until it is deposited within the synovial fluid.
Once within the synovial fluid, ibuprofen can act on
both the synoviocytes and the chondrocytes of the
articular cartilage, which obtain most of their nutrients
via diffusion from the synovial fluid [
reduces intra-articular inflammation by decreasing the
expression of pro-inflammatory cytokines, including
matrix metalloproteinase 3, matrix metalloproteinase 13,
interleukin 6, and tumor necrosis factor alpha [
Difference in Enantiomer Selection
Importantly, it has been shown that the S-enantiomer of
ibuprofen has a greater ability to diffuse into and stay
localized within the synovial joint than the R-enantiomer.
This is believed to be due to the higher serum protein
binding affinity of the R-enantiomer [
the S-enantiomer of ibuprofen has been shown to have
low cytotoxicity to both chondrocytes and synoviocytes,
making it an excellent candidate for use in transdermal
delivery, particularly for OA [
Formulation Techniques for Transdermal Ibuprofen
Multiple commercially available formulations of topical
ibuprofen exist, with most containing 5% by weight of
ibuprofen. However, despite the same concentration of
the drug, different products often exhibit significantly
variable uptake and delivery through the skin [
current areas of research include the development and
testing of superior formulations of transdermal
ibuprofen via a variety of drug delivery vehicles.
Supersaturations, microemulsions, nanosystems, and microneedles
are a few of the delivery mechanisms tested by
researchers in the search for the optimal transdermal
Supersaturated solutions of ibuprofen with disodium
hydrogen phosphate allow for higher concentrations of
ibuprofen in solution than would be possible under
normal circumstances. These have previously been shown
to greatly increase flux across the human epidermis,
indicating that they can disrupt and penetrate through the
stratum corneum [
]. Similar results were achieved
using the cellulosic polymer hydroxypropyl
]. Moreover, the combination of ibuprofen
sodium and polymer hydroxypropyl methylcellulose was
shown to inhibit nucleation and crystal growth,
prolonging drug supersaturation [
]. Despite these advances,
long-term stability of supersaturated solutions remains
an area of concern and active research.
and solubility in skin [
]. A later study also found that
ibuprofen-loaded microemulsions released comparable
amounts of the drug in vitro to a commercial ibuprofen
hydrogel, demonstrating their viability as a drug delivery
]. In an experiment measuring the effect of
saturated fatty acid length on the permeability of
ibuprofen transdermal microemulsions, medium-length fatty
acid-based microemulsions had low toxicity, good
permeability, and the highest analgesic activity [
group described an optimum formulation of a
microemulsion consisting of 6% oleic acid, 30% Cremophor
RH40/Transcutol (Xietai Chemical Co. Ltd., Shanghai,
China/Gattefosse, Shanghai, China) P (2:1, w/w), and
59% water phase that showed high permeation with no
signs of skin irritation [
Ibuprofen gels are commercially available and used in
clinical practice, but efforts continue to improve skin
permeability, bioavailability, and safety. An optimized
transdermal gel consisting of 5% ibuprofen, 30% ethanol,
and 10% POE [
]cetyl/oleyl ether had significantly
greater bioavailability than the two commercial gels
Ibutop® (Deutsche Chefaro Pharma GmbH, Germany)
and Senterlan® (Unicorn Laboratories, Hong Kong) [
Oxidized cellulose-based gels also exhibited similar in
vivo stratum corneum uptake and skin penetration
compared to over-the-counter marketed formulations,
despite 80% less drug loading [
While novel formulations of gels have been shown to be
superior to commercial products, even more promising
is the incorporation of nanosystems into transdermal
ibuprofen gel. Nanosystems allow for the production of
gels designed at the atomic and molecular level. For
example, an ethosomal ibuprofen gel containing 200 nm
unilamellar vesicles was applied transdermally in rats
and was found to have an efficient analgesic effect that
lasted at least 6 h with no evidence of skin irritation
]. Another gel using a nanostructured lipid carrier
improved diffusion through the epidermis compared to
traditional ibuprofen gel formulation by increasing the
lipophilicity of ibuprofen [
]. An ibuprofen
nanoliposome preparation containing phosphatidylcholine,
cholesterol, and dicetyl phosphate also showed superior skin
permeation in in vitro and in vivo experiments using
human skin [
Microemulsions (systems of oil, water, and an
amphiphilic compound) have similarly been shown to allow for
high concentrations of ibuprofen in solution (up to 3%).
Ethyl oleate, in particular, allows for greater permeability
Dissolvable microneedles can cross the stratum corneum
without damaging dermal nerves and blood vessels in
order to deliver drugs in a similar manner to
transdermal patches. They have repeatedly been demonstrated to
be an efficient way of directly introducing
pharmaceuticals into the dermis, including small molecules, vaccines,
and even large proteins [
ibuprofenladen dissolvable microneedles have been shown to
deliver local ibuprofen sodium effectively into rats .
However, these experiments suggest that high plasma
concentrations may be achieved in the process, negating
the safety advantages of transdermal ibuprofen over oral
delivery. In addition, absolute sterilization of
microneedles (which would ultimately be required by regulatory
bodies such as the US Food and Drug Administration
and the European Medicines Agency) cannot be
achieved by conventional methods without damaging
the vehicles. Gamma radiation has been explored as a
possible sterilization technique, yet even this elicits an
altered permeation profile of ibuprofen-laden
]. Greater optimization of microneedles is
needed to produce sterile and effective products with
minimal risk for toxicity.
Overall, novel formulations of transdermal ibuprofen
using diverse delivery methods have been demonstrated
to be safe and more efficacious than commercial
preparations in studies using both animal models and the
human epidermis. Optimum formulations using these
techniques should be incorporated into clinical trials
comparing the effectiveness of transdermal ibuprofen to
traditional methods of delivery.
Topical Ibuprofen vs Placebo and Non-Pharmacological
Topical ibuprofen has been demonstrated to be superior
to placebo in treating OA of the knee acutely [
45, 73, 74
These studies only focused on short-term outcomes of 1–
2 weeks, yet they demonstrated improved Western
Ontario and McMaster Universities Arthritis Index
(WOMAC) total, WOMAC physical function, and visual
analog scale pain scores during joint motion. Other
studies have shown that continuous ultrasound and topical
arnica are equally effective as topical ibuprofen in relieving
pain in knee OA and hand OA at 3 weeks, respectively
]. There is a paucity of data comparing the
longterm effects of topical ibuprofen and placebo in the
treatment of knee OA. This would be an interesting future
study, as there is some evidence suggesting that NSAIDs
may not be superior to placebo in reducing pain beyond
2 weeks in patients with knee OA [
Similar to OA, few studies have evaluated the efficacy
of topical ibuprofen in treating acute soft tissue injuries.
One study demonstrated a clinically meaningful
reduction in pain in 75% of patients using topical ibuprofen
compared to 39% of patients receiving placebo at 7 days
]. The same study found a significant reduction in
interference of physical activity in patients receiving
topical ibuprofen vs placebo, 79 and 44%, respectively
(p = 0.001). Another study concluded that topical
ibuprofen is superior to placebo in reducing visual analog
scale pain scores during rest, standing, and walking 48 h
post-treatment in acute ankle sprains (p < 0.05) [
Based on these studies, topical ibuprofen is likely
effective for treating acute soft tissue injuries, although
additional research is needed to provide more clarity.
Topical Ibuprofen vs Oral Ibuprofen
Oral ibuprofen has been a mainstay of treatment for
chronic and acute musculoskeletal pain for many years
and its efficacy is well-documented. However, given that
topical NSAIDs are theorized to have fewer side effects
than oral NSAIDs, it is important to understand if the
efficacy of topical ibuprofen is equal to the efficacy of
oral ibuprofen. The Topical or Oral Ibuprofen (TOIB)
study of 585 patients with chronic knee pain showed
that topical and oral ibuprofen demonstrated equivalent
changes global WOMAC scores at 12 months [
]. It is
important to note, however, that neither treatment
demonstrated a clinically or statistically significant reduction
in global WOMAC scores from baseline. A smaller
study of 20 patients with chronic knee pain treated with
topical or oral ibuprofen demonstrated equal significant
improvements at 2 weeks in WOMAC pain, stiffness,
and physical function scores [
]. These studies
demonstrate that topical ibuprofen is as effective as oral
ibuprofen in the treatment of chronic knee pain.
In one double-blind study of 100 patients with acute soft
tissue injuries, topical ibuprofen demonstrated equal time
to (1) being “completely better,” (2) significant relief of
pain at rest, (3) significant relief of pain while moving, and
(4) resolution of swelling when compared to oral
]. Every study that we examined above concluded
that topical ibuprofen has comparable efficacy to oral
ibuprofen, which should make it an attractive alternative in
the treatment of acute and chronic musculoskeletal
injuries given its favorable safety profile [
78, 81, 82
Bioavailability and Side Effects
One key advantage of topical ibuprofen use is its
decreased absorption and systemic distribution when
compared to oral ibuprofen. One study showed that plasma
concentrations of oral ibuprofen were 300 times that of
plasma concentrations of topical ibuprofen and that 0.55%
of administered topical ibuprofen is eliminated in the
urine in 24 h compared to 97% of oral ibuprofen [
Other studies have found that topical ibuprofen has
2–8% of the peak serum concentration of the
manufacturer’s reported plasma concentrations after oral
]. However, Kleinbloesem et al.
found that the dose-corrected bioavailability of topical
ibuprofen was 22% that of oral ibuprofen .
Though this is a much higher bioavailability than
found in the previously cited studies, this still
represents a fraction of the bioavailability found in oral
With the exception of the TOIB study, all of the clinical
trials included above in this paper reported no adverse
outcomes in either the oral ibuprofen or the topical
ibuprofen groups [
]. This is not entirely
surprising, as their follow-up times were all less than 3 weeks.
However, the TOIB study found no significant difference
in severe adverse effects requiring hospitalization
between patients taking oral or topical ibuprofen [
However, 16% of patients changed from oral to topical
ibuprofen due to adverse effects, while only 1% of
patients switched from topical to oral ibuprofen due to
adverse effects. In general, side effects of topical NSAIDs
occur in about 10–15% of patients and are
overwhelmingly cutaneous allergic reactions related to patches or
other topical preparations [
2, 78, 86, 87
]. Nevertheless, it
is important to note that because some topically applied
ibuprofen is absorbed and distributed systemically,
systemic side effects are still of concern.
Gastrointestinal Side Effects
A large review estimated that oral NSAIDs are
associated with a 15% incidence of adverse GI effects, whereas
adverse GI effects are very rare with topical NSAID use
]. In a case-controlled study that examined 1100
patients admitted to the hospital for upper GI bleeding or
ulceration, oral NSAIDs were strongly associated with
perforation (odds ratio 4.8, p < 0.001) and bleeding
(odds ratio 1.74, p < 0.001) [
]. However, topical
NSAID use was not associated with upper GI
perforation or bleeding, with an odds ratio of 0.86 (p = 0.89)
for perforation and 1.05 for bleeding (p = 0.86).
Although these previous two studies were not specific for
ibuprofen, they included both topical and oral ibuprofen
as parts of their NSAID aggregate.
Renal Side Effects
There is a scarcity of studies available that have directly
investigated the renal side effects of topical NSAIDs
relative to their oral counterparts. Prior studies indicate
the 24-h renal excretion of topical vs oral ibuprofen is
0.57 and 97%, respectively, suggesting that topical
therapy may be much safer in patients with renal
]. Furthermore, a case-control study of 207
patients hospitalized for acute renal failure concluded
that there was a minimal independent risk of renal
damage in those treated with topical NSAIDs [
However, two studies have documented cases of interstitial
nephritis resulting from topical ibuprofen and topical
]. Nevertheless, this risk was no greater
than that of oral NSAIDs and is in fact much less as
toxic systemic levels are rarely achieved with topical
Cardiovascular Side Effects
As with renal side effects, there is little literature that
explores the cardiovascular side effects of topically
administered ibuprofen. Oral ibuprofen, however, has been
repeatedly demonstrated to negatively affect aspirin’s ability
to prevent platelet aggregation and should be avoided
in athletes who are taking aspirin prophylactically to
avoid adverse events such as myocardial or cerebral
]. Although transdermally
administered ibuprofen’s decreased absorption and systemic
distribution may make it a safer option than oral
ibuprofen, there are few data in the literature to support
its use in the setting of concomitant aspirin use, and
more research in this field is required. Alternatively,
NSAIDs such as celecoxib and diclofenac (both oral
and transdermal) have already been shown to be safe
when used concurrently with aspirin and should be
considered instead [
95, 96, 99
A major drawback in using topical NSAIDs is the
increased cost associated with topical formulations. For
example, a 10-day treatment with oral ibuprofen would,
on average, cost about $3 for plain tablets, while a
10day supply of diclofenac gel would cost about $65 [
However, it is not entirely clear that oral NSAIDs are
less expensive than topical NSAIDs in patients treated
chronically. A study estimated that one third of the total
cost of treating patients with OA is dedicated to treating
the NSAID-induced adverse GI side effects that occur in
up to 25% of the patients [
]. A branch of the 2-year
TOIB study ambivalently concluded that oral NSAIDs
are probably less expensive when considering
qualityadjusted life years, although they emphasized the
importance of future research [
]. Cost is currently a
large barrier to recovering athletes who wish to receive
treatment with topical NSAIDs in the USA, as topical
formulations are more expensive than over-the-counter
oral formulations. Thus, they are typically reserved for
patients who cannot tolerate oral NSAIDs or are more
prone to side effects due to oral NSAIDs. However, the
increased cost associated with topical ibuprofen may be
partially offset by the decreased cost of treating
drugrelated side effects.
Ibuprofen is a NSAID that is widely used by injured
athletes to alleviate pain and inflammation associated soft
tissue injury and OA. Although oral administration of
ibuprofen is associated with numerous side effects,
topically administered ibuprofen allows for drug delivery
while reducing the risk of adverse GI, renal, and
cardiovascular side effects. Many different formulations have
been created in an attempt to increase diffusion of
ibuprofen through the skin and into its site of action,
including supersaturation, microemulsion, gel,
nanosystem, and microneedle techniques. Transdermal
ibuprofen delivery has been shown to be superior to placebo
and comparable to oral ibuprofen in terms of efficacy,
while also leading to fewer or less serious side effects.
Topical ibuprofen may also be more cost-effective in the
long term due to decreased rates of complications and
hospitalization. Further studies are needed to compare
topical efficacy to other transdermal delivery methods
and skin permeation enhancers. Comparative studies
between ibuprofen and other topical NSAIDs (e.g.,
diclofenac, ketoprofen) are also necessary to determine the
optimal pharmaceutical choice for acute soft tissue and
articular injury in athletes.
No Funding was received for the preparation of this manuscript.
Availability of Data and Materials
MACM, CWM, ART, JAH, and CD contributed to the conception, design,
research, and writing of this manuscript. All authors read and approved the
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Martin Manoukian, Christopher Migdal, Amode Tembhekar, Jerad Harris, and
Charles DeMesa declare that they have no conflicts of interest relevant to
the content of this review.
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