Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs

Shinkai, Norihiro; Korenaga, Kazuko; Okumura, Yutaka; Mizu, Hideo; Yamauchi, Hitoshi

doi:10.1016/j.ejpb.2011.03.005

Cited by 29 publications

(19 citation statements)

References 22 publications

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“…Among these applications, the assessment of in vivo skin absorption of drugs from topical and transdermal formulations has also been described (Schnetz, Fartasch, 2001;Kreilgaard, 2002;Brunner, Derendorf, 2006). Although the traditional pharmacokinetic evaluations assess the total drug in the sample (drug-protein binding and free drug fraction), this technique measures only the free drug fraction directly in the target tissue (Nakashima et al, 2006;Shearman et al, 2006;Zhang et al, 2007;Shinkai et al, 2011).Cutaneous microdialysis is classified as a semiinvasive technique in which a semipermeable microdialysis probe is inserted into defined skin layers (epidermis or dermis), directly under the formulation (Figure 3). The physiological solution (saline or Ringer's solution) is slowly perfused by using a pump (1-10 µL/min).…”

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confidence: 99%

“…Although tape-stripping only evaluates drug absorption in the stratum corneum, cutaneous microdialysis evaluates drug absorption in the depth layers of the skin. In these cases, cutaneous microdialysis enables characterization of skin absorption and clearance of drugs from topical formulations (Shinkai et al, 2011;Tang et al, 2013). Leveque et al (2004) studied the skin absorption of salicylic acid by using cutaneous microdialysis and compared the results with those from in vitro skin permeation studies using a Franz diffusion cell (Leveque et al, 2004).…”

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confidence: 99%

“…For these evaluations, a drug solution with known concentration is perfused for a defined time. Next, the drug concentration in the dialysate is determined (Kreilgaard, 2002;Brunner, Derendorf, 2006;Shinkai et al, 2011). The initial (C initial ) and final (C final ) concentrations are used in the determination of the relative recovery according to the Equation (1):…”

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Evaluation of skin absorption of drugs from topical and transdermal formulations

Ruela

Perissinato

Lino

et al. 2016

Braz. J. Pharm. Sci.

217

135

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The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed. Uniterms:Skin absorption/effects/study. Skin absorption/topical formulations. Skin absorption/ transdermal formulations. Skin absorptions/enhancers. INTRODUCTIONTopical and transdermal drug delivery systems have shown significant advantages in clinical practice for drug targeting to the action site in the body; this has reduced the systemic side effects. The administration of drugs by through the skin is also performed to achieve controlled or prolonged drug delivery, and this route can be explored as an alternative to the oral route. The oral route shows some limitations for drugs with irregular absorption in the gastrointestinal tract and low bioavailability and for drugs with increased first pass metabolism and short plasma halflife times (Barry, 2001;Wokovich et al., 2006;Prausnitz, Langer, 2009;Alexander et al., 2012).Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected. This is the case for topical formulations for treatment of skin disorders such as acne and cutaneous inflammatory diseases that include dermatitis, erythematous lupus, and psoriasis. On the other hand, transdermal formulations release drugs that permeate through the skin and enter the systemic circulation. Transdermal therapy must ensure that significant concentrations of the drug are absorbed to reach effective plasma concentrations. Permeation of drugs is targeted in some cases to body regions close to the action site, where a regional effect is expected, e.g., in the muscles, blood vessels, and articulations. In this way, the term "cutaneous absorption" is properly used to characterize the sum of the amounts of drug that penetrate and permeate the skin (Barry, 2001;El Maghraby, Barry;Willi...

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Evaluation of skin absorption of drugs from topical and transdermal formulations

Ruela

Perissinato

Lino

et al. 2016

Braz. J. Pharm. Sci.

217

135

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“…Therefore, it is necessary to develop enhancement techniques to assist the skin penetration of KET, and extensive research has been done to find both topical and transdermal KET formulations. 1,[4][5][6] To improve the delivery of KET through the skin, several techniques have been employed as follows: liposomes, 7) gels, 8,9) ointments, creams, 10) patches 11,12) incorporating various permeation enhancers, micro-needle treatment, 13) iontophoresis 14,15) and therapeutic frequency sonophoresis (1 MHz). 16,17) Recently, strategies using nanoparticles have been developed and investigated as nanomedicines.…”

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Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles

Nagai

Iwamae

Tanimoto

et al. 2015

Biological & Pharmaceutical Bulletin

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We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KET nano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KET nano gel ointment was prepared using a bead mill method and additives including methylcellulose and Carbopol 934; the mean particle size of the KET nanoparticles was 83 nm. In the in vitro skin penetration experiment, the penetration rate (J c ) and penetration coefficient through the skin (K p ) values of the KET nano gel ointment were significantly higher than those of gel ointment containing KET microparticles (KET micro gel ointment; mean particle size 7.7 µm). On the other hand, in the in vivo percutaneous absorption experiment, the apparent absorption rate constant (k a ) and the areas under the KET concentration-time curve values in the skin of rats receiving the KET nano gel ointment were significantly higher than those of rats receiving the KET micro gel ointment, and the amounts of KET in the skin tissues of rats receiving the KET nano gel ointment were also significantly higher than those of rats receiving the KET micro gel ointment. In addition, the application of the KET nano gel ointment attenuated the enhancement of paw edema of the hind feet of AA rats more than the application of the KET micro gel ointment. Our findings suggest that a topical drug delivery system using nanoparticles could lead to expansion in the therapeutic use of KET.Key words nanoparticle; ketoprofen; gel ointment; drug delivery; adjuvant-induced arthritis Ketoprofen (KET) is a reversible inhibitor of cyclooxygenases 1 and 2 whose action leads to a reduction in the formation of prostaglandin precursors. 1) Thus, KET acts as an antiinflammatory agent, and is used in the treatment of rheumatoid arthritis (RA) and osteoarthritis. However, its usefulness is limited due to its low water solubility and the fact that oral administration of KET tends to cause gastrointestinal lesions in 10-30% of patients. These gastrointestinal lesions lead to an interruption of drug therapy in about 5-15% patients. 2,3)Topical and transdermal delivery routes of drug administration reduce the incidence of gastrointestinal lesions and improve patient compliance. Furthermore, the transdermal route of application avoids hepatic first pass metabolism, meaning that therapeutic serum drug concentrations can be applied with a reduced risk of nephrotoxicity and drug-drug interactions.2) However, the transdermal route of application is limited by the barrier properties of the skin. Therefore, it is necessary to develop enhancement techniques to assist the skin penetration of KET, and extensive research has been done to find both topical and transdermal KET formulations.

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“…FDA and European Union's Committee emphasized the value of human-tissue drug concentration data and support the application of clinical MD to obtain pharmacokinetic information (Nandi and Lunte, 2009); this recommendation indicates the potential and importance of MD. Recently, MD has also been extensively employed for pharmaceutical applications and neuroscience research (Shinkai et al, 2011;Zhang et al, 2011;Guo et al, 2012;Yu et al, 2013).…”

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confidence: 99%

Pharmacokinetics of aconitine-type alkaloids after oral administration of Fuzi (Aconiti Lateralis Radix Praeparata) in rats with chronic heart failure by microdialysis and ultra-high performance liquid chromatography–tandem mass spectrometry

Cao

Yao-kang

2015

Journal of Ethnopharmacology

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Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs

Cited by 29 publications

References 22 publications

Evaluation of skin absorption of drugs from topical and transdermal formulations

Evaluation of skin absorption of drugs from topical and transdermal formulations

Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles

Pharmacokinetics of aconitine-type alkaloids after oral administration of Fuzi (Aconiti Lateralis Radix Praeparata) in rats with chronic heart failure by microdialysis and ultra-high performance liquid chromatography–tandem mass spectrometry

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