Transfersome Gel Research Articles

Formula Optimization of Propolis Transfersome Gel, Aloe Vera, Gotu Extract: Formula Design, Formulation Evaluation and Cell Regeneration Test in Diabetic Wounds

The study was conducted to determine the optimal formula of transfersome propolis gel, aloe vera extract and gotu gotu leaf extract and test it against diabetic wounds in male white rats (Rattus norvegicus). The gel was created with an optimal formulation resulting from the application of a Design Expert with Cutimed as a positive control of burns on the backs of male white rats (Rattus norvegicus). Formula optimization was carried out using a Simple Lattice Design with variations of carbopol, TEA and glycerin. Activity tests of propolis transferosome gel, aloe vera extract and gotu gotu extract were conducted on 20 rats. The data results were statistically analyzed using the SPSS One Way ANOVA method. Phytochemical screening on aloe vera and gotu gotu showed the presence of flavonoid compounds, tannins and saponins. Transfersome propolis has a particle size of 88.55 nm and a zeta potential of -24.13 mV. The optimal formula produces a clear preparation in white, a distinctive odour, a stable viscosity of 19980 cps, dispersion power of 6.67 cm, adhesion of 4.07 seconds and pH of 6.45. The burn activity test had the fastest effectiveness on day 12 but did not differ significantly from the customized control.

Ameliorative effect of transfersome gel of kepok banana peel extract (Musa balbisiana) against photoaging in Wistar rat skin.

Repeated acute exposure to ultraviolet B (UVB) rays can cause photoaging. Musa balbisiana peel contains flavonoid compounds which act as antioxidants. However, the physicochemicals of flavonoids are unstable, have high molecular weight, and are easily oxidized, causing their use is still limited and transdermal delivery to be inefficient. To investigate the ameliorative effect of transfersome gel of M. balbisiana peels against photoaging in Wistar rat skin. Transfersome gel was characterized by transmission electron microscopy (TEM). In vivo research was used to determine the ameliorative effects of M. balbisiana peel. The composition of transfersome consists of ethanol extracts of M. balbisiana peel, soybean phosphatidylcholine, and tween 80. The gel was applied three times a week for 4 weeks with a total UVB radiation dose of 840 mJ/cm2. To evaluate the repair mechanism by measuring the degree of wrinkles, epidermal thickening, dermal thinning, collagen fiber irregularity, matrix metalloproteinase 1 (MMP-1), and transforming growth factor-β (TGF-β) expression, malondialdehyde (MDA) and tumor necrosis factor-α (TNFα) levels. TEM results show that gel transfersome M. balbisiana peel has a round morphology with a diameter of ±50 nm and no aggregation, which are defined as nanoparticles. Transfersome gel ameliorated the degree of wrinkle, epidermal thickening, dermal thinning, and irregularity of collagen fibers caused by UVB exposure, suppresses lipid peroxidation by decreasing MDA and TNFα level, also collagen imbalance by inhibiting MMP-1 expression and activating TGF-β expression, which was found statistically significantly different from non-transfersome gel group. Transfersome gel of M. balbisiana peel can act as an alternative medicine to ameliorate clinical photoaging due to exposure to UVB.

Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation.

Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between Phl molecules results in poor water solubility and low bioavailability, and thus the scope of the clinical application of Phl is limited. Therefore, it is particularly important to improve the water solubility of Phl for its use to further combat or alleviate skin aging and oxidative damage and develop antioxidant products for the skin. The purpose of this study was to develop and evaluate a phloretin transfersome gel (PTG) preparation for transdermal drug delivery to improve the bioavailability of the drug and delay aging. Phloretin transfersomes (Phl-TFs) were prepared and optimized by the thin-film dispersion-ultrasonication method. Phl-TFs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The Log P method was used to determine the solubility of the Phl-TFs. The skin penetration ability of the prepared PTG was evaluated using the Franz diffusion cell method. In addition, the in vivo pharmacokinetics of PTG were studied in rats, and an antioxidant activity investigation was conducted using a D-gal rat model. Phl-TFs were successfully prepared with a Soybean Phosphatidylcholine (SPC)/CHOL ratio of 2.7:1 w/v, a phloretin concentration of 1.3 mg/mL, a hydration time of 46 min, an ultrasound time of 5 min, and an ultrasound power of 180 W. The Log P was 2.26, which was significantly higher than that of phloretin (p < 0.05, paired t test). The results of the in vitro penetration test demonstrated that the cumulative skin penetration of the Phl-TFs after 24 h was 842.73 ± 20.86 μg/cm2. The data from an in vivo pharmacokinetic study showed that the Cmax and AUC of PTG were 1.39- and 1.97-fold higher than those of the phloretin solution gel (PSG), respectively (p < 0.05, paired t test). The experimental results in aging rats showed that PTG had a better antioxidant effect. Phl-TFs and PTG preparations with a good shape, safety, and stability were successfully prepared. In vivo pharmacokinetics and preliminary antioxidant experiments further verified the transdermal penetration and antioxidant activity of the phloretin transdermal drug delivery preparation, providing an experimental basis for its further development.

EFFECT OF SKIN FAT ON CAPSAICIN TRANSFERSOME GEL: IN VITRO PENETRATION STUDIES USING FRANZ DIFFUSION CELLS

Objective: Capsaicin is a highly lipophilic substance that generally uses an organic cosolvent added to diffusion medium in penetration tests to increase penetration by fluidizing fat. This study aims to determine the effect of subcutaneous fat on the penetration of capsaicin as lipophilic substances formulated into transfersome and compare it to hydrophilic substances, namely vitamin C. Methods: The thin layer method was used to develop the transfersome formulation using Phospholipon 90G and Tween 80. Vesicle size, zeta potential, deformability index, morphology, and entrapment efficiency were all characterized. The transfersome suspension was then developed into a gel formulation using 1% carbomer. The in vitro penetration test was performed using a Franz diffusion cell of rat skin with and without subcutaneous fat. Results: The cumulative amount of penetration on fat-free membranes compared to membranes with fat for capsaicin transfersome gel 920.28±3.42 μg/cm2 and 762.22±1.73 μg/cm2, respectively, then for non-transfersome capsaicin gel was 833.33±0.84 μg/cm2 and 595.80±0.32 μg/cm2 respectively, and for vitamin C non-transfer some gel 776.45±1.19 μg/cm2 and 654.69±3.36 μg/cm2 respectively. Conclusion: According to these results, it can be concluded that the presence of subcutaneous fat affects inhibiting the penetration of lipophilic substances.

Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma

BackgroundTopical anticancer drugs offer a potential therapeutic modality with high compliance for treating cutaneous squamous cell carcinoma (cSCC). However, the existing topical treatments for cSCC are associated with limited penetrating ability to achieve the desired outcome. Therefore, there remains an urgent requirement to develop drugs with efficient anticancer activity suitable for treating cSCC and to overcome the skin physiological barrier to improve the efficiency of drug delivery to the tumor.ResultsWe introduced lycorine (LR) into the topical treatment for cSCC and developed a cell-penetrating peptide (CPP)-modified cationic transfersome gel loaded with lycorine-oleic acid ionic complex (LR-OA) (LR@DTFs-CPP Gel) and investigated its topical therapeutic effects on cSCC. The anti-cSCC effects of LR and skin penetration of LR-OA transfersomes were confirmed. Simultaneously, cationic lipids and modification of R5H3 peptide of the transfersomes further enhanced the permeability of the skin and tumor as well as the effective delivery of LR to tumor cells.ConclusionsTopical treatment of cSCC-xenografted nude mice with LR@DTFs-CPP Gel showed effective anticancer properties with high safety. This novel formulation provides novel insights into the treatment and pathogenesis of cSCC.

Stability of High Concentration Capsaicin in Transfersome Carriers in Gel Dosage Form

Topical capsaicin with high concentrations (8%) is effective in the treatment of pain in Post-Herpetic Neuralgia (PHN) and HIV-Associated Distal Sensory Polyneuropathy (HIV-DSP) patients. High concentrations of capsaicin encapsulated in transfersome nanovesicles aim to reduce the irritating ability of capsaicin when using as drugs. Gel preparations were chosen in the formulation because they are non-sticky, easy to wash, easy to apply, and more practical. The components contained in the gel affect the stability of the gel. Physical and chemical stability tests need to be carried out to ensure the quality, safety and efficacy of the gel so that it meets the expected specifications during its shelf life. This study aims to determine the stability of selected gel formulas containing high concentrations of transfersome capsaicin. The selected gel formula is a gel containing a mixture of phosphatidylcholine (Phospholiphon 90G®) and Tween 80 (80:20). Stability was carried out at high temperature (40±2oC), room temperature (30±2oC), low temperature (5±3oC), and cycling test. The stability parameters tested included organoleptic, pH, viscosity, and assay. The results of the transfersom capsaicin gel stability test showed no change in pH, viscosity, and assay in all storage conditions, but the gel showed a change in color, smell, and taste when stored at high temperatures (40 ± 2oC). It can be concluded that the resulting capsaicin transfersome gel formula with a phospholipid:tween ratio of 80 (80:20) was less stable during 12 weeks of storage at 40 oC

Formulation and characterization of transfersome gel from Parkia speciosa extract using carbopol 940 and polyvinyl alcohol

Formulation and characterization of transfersome gel from Parkia speciosa extract using carbopol 940 and polyvinyl alcohol

Development of a Novel Freeze-dried Mulberry Leaf Extract-based Transfersome Gel.

Nowadays, antioxidants are important for health-related concerns related to acne vulgaris. Acne vulgaris is interrelated with the development of free radicals that interact with cells. Mulberry leaves contain phenolic compounds, including antioxidants such as quercetin. An antioxidant is a scavenger of free radicals. The current study addresses the development of a mulberry leaf extract-based transfersome gel containing quercetin by a thin-layer hydration method for topical antioxidant delivery. The process was optimized by encapsulating the drug in a variety of transfersome formulations. Batch optimization was carried out by particle size and zeta analysis, entrapment efficiency (%), polydispersity index, in vitro drug release, and drug content analysis. The optimized batch MF5 provided 86.23% entrapment efficiency of quercetin in the vesicles and 95.79% drug release. It furnished a spherical shaped vesicle with an average diameter of 118.7 nm and zeta potential of -45.11 mV. The MG1 formulation provided superior antioxidant activity, drug content, and entrapment efficiency, ex vivo drug release, spreadability, homogeneity, and stability to MG2. The presence of quercetin in the extract and gel formulation was confirmed by using high performance thin layer chromatography. It is evident from this study that a mulberry leaf extract-based transfersome gel is a promising prolonged delivery system for quercetin and has reasonably good stability characteristics. This research recommends that mulberry leaf extract-based transfersome gel can potentially be used in the treatment of acne vulgaris through a transdermal drug delivery system.

FORMULATION OF ANDROGRAPHOLIDE TRANSFERSOMES GEL FOR TRANSDERMAL DELIVERY: A PRELIMINARY STUDY

Objective: A transfersome is a drug delivery system that offers increased penetration for the transdermal delivery of drugs. The aim of this study wasto assess the application of transfersomes for transdermal delivery of andrographolide.Methods: The development of andrographolide transfersomes for transdermal delivery was conducted in two steps. The first step involved varyingratios of Span 80 and phospholipids to investigate the effect on transfersome deformability using four formulations (P1–P4). Afterward, a second stepinvolved varying ratios of andrographolide in transfersomes to investigate the influence on entrapment efficiency using four formulations (F1–F4).The selected transfersomes were then formulated into a gel dosage form. An in vitro penetration study was conducted by comparing the penetrationfluxes of the transfersome and non-transfersome andrographolide gels using Franz diffusion cells.Results: The results showed that formulation F4 had an entrapment efficiency of 97.02±0.01% and particle size (DV-average) of 524.02 nm. An in vitropenetration study of the andrographolide transfersome gels showed two phases of penetration, with a marked increase in both fluxes. In the firstphase, penetration flux was 23.26±2.34 and 1.28±0.82 μg/cm2·h for the transfersome and non-transfersome andrographolide gels, respectively.Conclusion: The results showed that the transfersome gel is a promising dosage system for transdermal delivery of andrographolide.

Development and Investigation of Vitamin C-Enriched Adapalene-Loaded Transfersome Gel: a Collegial Approach for the Treatment of Acne Vulgaris.

Adapalene-loaded transfersome gel containing vitamin C as a combination therapy for the management of acne vulgaris was developed in the present study. The transfersome was prepared by reverse-phase evaporation, and the effect of various process parameters were investigated by the Design of Experiment (DOE) approach and optimized based on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The selected tranfersomes were further evaluated for their thermal behavior and morphology by transmission electron microscopy and turbidity measurements and incorporated into a gel with/without vitamin C. The gel was evaluated and compared with the marketed product (Adiff gel) for various physicochemical parameters, and in vivo studies in testosterone-induced rat models of acne. The prepared transfersomes had PS in the range of 280 to 400nm, PDI values of 0.416 to 0.8, ZP of - 38 to - 20mV, and % EE of 32 to 70%. DSC studies confirmed a positive interaction of the components in the transfersome. Surface morphology confirmed that the vesicles were spherical, unilamellar, and discrete. A relative deformability study showed higher elasticity of the transfersomes compared with Adiff aqs gel. Ascorbyl-6-palmitate in adapalene-loaded transfersome gel containing vitamin C (ADVTG) was found to have a good antioxidant free radical-scavenging activity. An in vitro drug release study showed that the sustained release of the transfersomal formulations was attributed to the flexibility of the vesicles by which penetration was increased. ADVTG was found to be promising in treating acne compared with the marketed product. Graphical Abstract.

PHYSICAL STABILITY TESTING OF P-SYNEPHRINE PREPARED AS TRANSFERSOME GEL

Objectives: While p-synephrine exhibits lipolytic activity, it also has a low oral bioavailability as well as hydrophilic characteristic, so it is difficult forit to penetrate the epidermis if it is made into transdermal preparation. The purpose of this research was to increase the penetration of p-synephrineby preparing it as transfersome gel.Materials and Methods: Three transfersome formulas were prepared—F1, F2, and F3—with the surfactants used at Tween 80, Span 80, and thecombination of Tween 80 and Span 80 with a ratio of 1:1, respectively.Results: The results showed that F1 was the best formula, with the highest entrapment efficiency, of 64.058±0.754%, a particle size average of103.3 nm, polydispersity index 0.269±0.05, and zeta potential of −36.2±0.64 mV, so this formula was employed for the gel formulation. Two gelformulas were then prepared, transfersome gel (GT) and non transfersome gel (GNT).Conclusions: The two gels were evaluated for their physical stability, and GT was found to be more stable than GNT.

EFFECT OF HYDROPHILICITY SURFACTANTS TOWARD CHARACTERIZATION AND IN VITRO TRANSFERSOMES PENETRATION IN GELS USING FRANZ DIFFUSION TEST

Objective: Capsaicin is a bioactive compound with poor solubility in water. Transfersomes can increase the solubility and thus the penetration ofcapsaicin into the epidermis. Transfersomes also offer the advantage of being ultradeformable vesicles that are made using the thin layer hydrationmethod. The aim of this study is to determine the effect of the hydrophilicity of surfactants on the characterization and in vitro penetrative ability ofcapsaicin transfersomes in gels using non-ionic surfactants with different hydrophile-lipophile balances, namely, Span 80, Tween 80, and a mixtureof Span 80, and Tween 80.Methods: The best characterization result for transfersomes is the formula using Tween 80. The total cumulative amount of capsaicin penetratedfrom the transfersome gel using Tween 80 is 1663.89±1.58 mg/cm2, the percentage is 57.96±0.05%, and the flux is 166.38±0.15 μg/cm2.hr−1.Results: In terms of the transfersome gel using a mixture of Span 80 and Tween 80, the cumulative amount of capsaicin penetrated is1539.8±21.23 μg/cm2, the percentage is 54.47±0.75%, and the flux is 153.98±2.12 μg/cm2.hr−1. Finally, from the transfersome gel using Span 80, thecumulative amount of capsaicin penetrated is 1395.10±7.23 mg/cm2, the percentage is 50.80±0.26%, and the flux is 139.51±0.72 mg/cm2.hr−1.Conclusions: The best characteristics resulted from the transfersome formulation using Tween 80, which demonstrated the highest entrapmentefficiency calculation result, the smallest particle size, the best deformability index, and the highest penetration when compared to the other twoformulations.

TRANSFERSOME GEL FORMULATION OF AN ETHANOL EXTRACT OF APPLES (MALUS DOMESTICA MILL) CONTAINING ANTIOXIDANTS AND IN VITRO PENETRATION TESTING USING FRANZ DIFFUSION CELLS

Objective: This study aims to formulate and characterize a transfersome apple peel extract, formulate it into a gel, and compare it with a control gelmade without transfersome.Methods: Both gels were evaluated, stability tested, and penetration tested using Franz diffusion cells on the skin of female Sprague-Dawley rats. Thetransfersome preparations were formulated with different concentrations of the active substance, quercetin: 0.5% (F1); 0.7% (F2), and 1.0% (F3).Results: Based on the characterization results, F1 was selected as the optimum gel formulation because it had spherical morphology, a Dmean volume of106.44±2.70 nm, a polydispersity index of 0.078±0.01, a zeta potential of −49.96±2.05 mV, and a drug efficiency entrapment percentage of 78.78±0.46%.The cumulative amount of quercetin that was penetrated with the transfersome gel was 1514.41±26.31 μg/cm2, whereas the penetration with thecontrol gel extract was 1133.62±18.96 μg/cm2. The cumulative percentages of the penetrated gel transfersome and gel extract were 78.40±1.89%and 49.89±0.88%, respectively. The fluxes of transfersome gel and control gel extract were 52.33±0.11 μg/cm²/hrs and 40.89±0.68 μg/cm²/hrs,respectively.Conclusions: Based on these results, it can be concluded that the gel with transfersome exhibited better penetration than the gel extract alone.

Safety and efficacy of topical ketoprofen in transfersome gel in knee osteoarthritis: A systematic review.

Topical ketoprofen in Transfersome gel has been used for the alleviation of symptoms in osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with various side effects. Topical NSAIDs are known to have a lower side-effect profile when compared with systemic administration. The present systematic review aimed to determine the safety and efficacy of topical ketoprofen in Transfersome gel in knee osteoarthritis (OA). A systematic literature review was performed. The electronic databases EMBASE, MEDLINE, HealthStar and PubMed were searched from 1946 to June 2016. A screen of the reference sections of the included studies was also performed. Two blinded reviewers searched, screened, abstracted and evaluated the data quality using the Jadad scale. Studies were included if they contained: at least 50% of participants with knee OA, topical ketoprofen, human subjects and participants from North America or Europe. Study outcomes had to include patient-reported functional outcome scores. Five studies were included, with a total of 3619 participants, and a mean Jadad score of 3.4/5. Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index was the only outcome measure consistent across all of the randomized controlled trials included in the present review (four of the five included studies). All topical ketoprofen in Transfersome gel groups (25mg, 50mg and 100mg) had improvements in pain that were superior to all other treatment arms, and the 50mg topical ketoprofen in Transfersome gel group had functional gains that were superior to all other treatment arms. The majority of the adverse events were non-serious and related to skin and subcutaneous tissue disorders, with erythema being the most common. The average of all adverse events and gastrointestinal (GI) adverse events was highest in the oral celecoxib group (47.1% and 15.1%, respectively). The average frequency of GI adverse events in the topical ketoprofen groups was comparable with that in the topical placebo treatment arm. A meta-analysis was not feasible due to the heterogeneity among the studies. Topical ketoprofen in Transfersome gel is an effective means of treating symptoms of knee OA, and is superior to oral celecoxib, oral placebo and topical placebo. The most commonly reported adverse events associated with the use of topical ketoprofen in Transfersome gel were non-severe skin and subcutaneous tissue disorders. Furthermore, as topical ketoprofen in Transfersome gel was associated with fewer adverse events when compared with oral celecoxib, and had rates of GI adverse events comparable with those of topical placebo, it may be ideal for those who are unable to take oral NSAIDs.

A Randomized, Double-blind, Phase III Trial in Moderate Osteoarthritis Knee Pain Comparing Topical Ketoprofen Gel with Ketoprofen-free Gel

This randomized, double-blind, phase III study evaluated the efficacy and safety of ketoprofen in an ultradeformable vesicle gel compared with ketoprofen-free gel in osteoarthritis (OA) knee pain. Patients with American College of Rheumatology-defined OA of the knee and moderate pain were randomized to receive 100 mg ketoprofen in 4.4 g transfersome gel (IDEA-033) or 4.4 g ketoprofen-free vehicle (TDT 064) topically, twice daily, for 12 weeks. The primary endpoint was mean change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score from baseline to Week 12. Patients (n = 555) were randomized and treated. Mean baseline WOMAC pain scores were 5.2 (SD 1.0) for IDEA-033 and 5.3 (SD 1.0) for TDT 064. Mean change in WOMAC pain scores from baseline to Week 12 was 38.6% for IDEA-033 and 44.6% for TDT 064 (Mann-Whitney estimator 0.4505; p = 0.022). Both groups reported progressive decreases in pain and improvements in function and stiffness. Mean baseline WOMAC function scores decreased from 5.4 to 3.4 with IDEA-033 and 3.1 with TDT 064 at Week 12. The proportion of patients achieving ≥ 50% decrease in WOMAC pain score from baseline at Week 12 was 41.2% (95% CI 0.35-0.47) with IDEA-033 and 50.5% (95% CI 0.45-0.57) with TDT 064. Mild skin and subcutaneous tissue disorders were the most frequently reported treatment-related adverse events (AE). IDEA-033 was inferior to drug-free gel (TDT 064) in relieving moderate OA knee pain and improving joint function.

SAT0329 A double-blind, placebo-controlled trial comparing the safety and efficacy of epicutaneously applied ketoprofen in transfersome gel with naproxen for the treatment of pain associated with osteoarthritis (OA) of the knee

BackgroundIDEA 033 is a formulation of ketoprofen in Transfersome – ultra-deformable carriers – that is applied epicutaneously for the treatment of pain associated with OA, thus minimising the potential for...

AB0990 A double-blind, randomised, placebo-controlled trial to evaluate the safety and efficacy of epicutaneously applied ketoprofen in transfersome gel for the treatment of pain associated with osteoarthritis (OA) of the knee

BackgroundIDEA 033 is an epicutaneously applied formulation of ketoprofen in Transfersome – aqueous dispersion of ultra-deformable carriers – for the treatment of pain in OA, which potentially minimises systemic adverse...

FRI0300 A large randomised, controlled trial comparing the efficacy and safety of topical ketoprofen in transfersome gel with oral celecoxib for osteoarthritis knee pain

BackgroundIDEA 033 is a topically applied osteoarthritis (OA) treatment that uses novel Transfersome (TM IDEA AG) – an aqueous dispersion of ultra-deformable carriers – to deliver ketoprofen to soft tissue.ObjectivesTo...

A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis

To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS; A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12. A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg). IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.

Efficacy of epicutaneous Diractin&amp;reg; (ketoprofen in Transfersome&amp;reg; gel) for the treatment of pain related to eccentric muscle contractions

To investigate the effect of epicutaneously applied Diractin (ketoprofen in Transfersome gel) on pain induced by eccentric muscle contractions. Three pilot studies which were subsequently pooled for a meta-analysis compared the efficacy of a single application of 25 mg ketoprofen in Diractin to 25 mg oral ketoprofen and placebo for the treatment of pain induced by 50 eccentric contractions of the elbow flexor muscles. In addition, the effect of multiple usage of up to 100 mg ketoprofen in Diractin bid over seven days on pain induced by walking down stairs with a total altitude of 200 meters was investigated. A single dose of 25 mg ketoprofen in Diractin after the elbow flexion exercise was significantly superior to placebo from 5 to 12 hours after treatment and also to oral ketoprofen at some time points after treatment. In contrast, oral ketoprofen was not different to placebo at any time after treatment. Multiple doses of up to 100 mg ketoprofen Diractin provided significant more pain relief than placebo on muscle pain induced by walking down stairs. Eccentric exercise-induced muscle soreness was shown to be an appropriate acute pain model to evaluate the efficacy of nonsteroidal anti-inflammatory drugs applied epicutaneously with Transfersome carriers. Diractin proved to be efficacious in relieving pain from eccentric muscle contractions and muscle over-exercise, respectively. The effect needs to be confirmed in a larger prospective clinical trial.