Effects of Ethylcellulose and 2-Octyldodecanol Additives on Skin Permeation and Irritation with Ethylene-Vinyl Acetate Copolymer Matrix Patches Containing Formoterol Fumarate

Kakubari, Ikuhiro; Sasaki, Hiroyuki; Takayasu, Toshiyuki; Yamauchi, Hitoshi; Takayama, Satoshi; Takayama, Kozo

doi:10.1248/bpb.29.1717

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…These solvents are an unsaturated fatty acid ester and aliphatic fatty alcohol, respectively, and they have been reported to be able to disturb the SC bilayers and promote drug permeation by lowering the diffusional resistance of the lipid domain [ 54 ]. Kakubari et al (2006) examined the in vitro human skin permeation of formoterol fumarate from transdermal patches containing differing concentrations of OD, either 0.5 mg/cm 2 or 1 mg/cm 2 [ 55 ]. The incorporation of OD was reported to significantly enhance drug permeation compared to the control patch without OD.…”

Section: Resultsmentioning

confidence: 99%

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Iliopoulos¹,

Goh

Haque³

et al. 2022

Pharmaceutics

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Previously, we reported the use of confocal Raman spectroscopy (CRS) as a novel non-invasive approach to determine drug disposition in the skin in vivo. Results obtained by CRS were found to correlate with data from the well-established in vitro permeation test (IVPT) model using human epidermis. However, these studies used simple vehicles comprising single solvents and binary or ternary solvent mixtures; to date, the utility of CRS for monitoring dermal absorption following application of complex marketed formulations has not been examined. In the present work, skin delivery of diclofenac sodium (DFNa) from two topical dermatological drug products, namely Diclac® Lipogel 10 mg/g and Primofenac® Emulsion gel 1%, was determined by IVPT and in vivo by both CRS and tape stripping (TS) methodologies under similar experimental conditions. The in vivo data were evaluated against the in vitro findings, and a direct comparison between CRS and TS was performed. Results from all methodologies showed that Diclac promoted significantly greater DFNa delivery to the skin (p < 0.05). The cumulative amounts of DFNa which permeated at 24 h in vitro for Diclac (86.5 ± 9.4 µg/cm2) were 3.6-fold greater than the corresponding amounts found for Primofenac (24.4 ± 2.7 µg/cm2). Additionally, total skin uptake of DFNa in vivo, estimated by the area under the depth profiles curves (AUC), or the signal intensity of the drug detected in the upper stratum corneum (SC) (4 µm) ranged from 3.5 to 3.6-fold greater for Diclac than for Primofenac. The shape of the distribution profiles and the depth of DFNa penetration to the SC estimated by CRS and TS were similar for the two methods. However, TS data indicated a 4.7-fold greater efficacy of Diclac relative to Primofenac, with corresponding total amounts of drug penetrated, 94.1 ± 22.6 µg and 20.2 ± 7.0 µg. The findings demonstrate that CRS is a methodology that is capable of distinguishing skin delivery of DFNa from different formulations. The results support the use of this approach for non-invasive evaluation of topical products in vivo. Future studies will examine additional formulations with more complex compositions and will use a wider range of drugs with different physicochemical properties. The non-invasive nature of CRS coupled with the ability to monitor drug permeation in real time offer significant advantages for testing and development of topical dermatological products.

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Section: Resultsmentioning

confidence: 99%

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Iliopoulos¹,

Goh

Haque³

et al. 2022

Pharmaceutics

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“…It is well known that rodent skin is generally more permeable than human skin (Catz & Friend 1990;Kakubari et al 2006), while drug permeability in pig skin is similar to that in man (Ngawhirunpat et al 2004). Human skin permeability of felbinac after application of the patch may be poor compared with rat skin.…”

Section: Effects On Incisional Painmentioning

confidence: 99%

Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats

Shinkai¹,

Korenaga²,

Takizawa³

et al. 2008

Journal of Pharmacy and Pharmacology

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We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.

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“…Octyldodecanol (0.5, 1.00 mg/ in 2 ) increased the dermal penetration of formoterol fumarate. 68 Octyldoddecanol was not irritating to rabbit skin alone but increased the irritation of formoterol fumarate from a score of 0.21 (control) to 1.38. No irritation was observed in guinea pigs, rats, and miniature swine.…”

Section: Octyldodecanol: Metabolite Of Dioctyldodecyl Malatementioning

confidence: 91%

Safety Assessment of Dialkyl Malates as Used in Cosmetics

Becker¹,

Bergfeld²,

Belsito³

et al. 2015

Int J Toxicol

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The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 6 dialkyl malate compounds used in cosmetics. These ingredients function mostly as skin-conditioning agents-emollients. The Panel reviewed relevant animal and human data related to the ingredients along with a previous safety assessment of malic acid. The similar structure, properties, functions, and uses of these ingredients enabled grouping them and using the available toxicological data to assess the safety of the entire group. The Panel concluded that these dialkyl maleate compounds are safe in the present practices of use and concentration as given in this safety assessment.

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Effects of Ethylcellulose and 2-Octyldodecanol Additives on Skin Permeation and Irritation with Ethylene-Vinyl Acetate Copolymer Matrix Patches Containing Formoterol Fumarate

Cited by 5 publications

References 20 publications

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats

Safety Assessment of Dialkyl Malates as Used in Cosmetics

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