A review of the nonclinical safety of Transcutol®, a highly purified form of diethylene glycol monoethyl ether (DEGEE) used as a pharmaceutical excipient

Sullivan, Dexter W.; Gad, Shayne C.; Julien, Marjorie

doi:10.1016/j.fct.2014.06.028

Cited by 97 publications

(66 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…46 It is reported to increase the permeability of the drugs 48,49 and is listed in the Food and Drug Administration Inactive Ingredients Database for topical use. 50 Capmul MCM EP (mono/diglycerides of capric acid) is an emulsifier and natural lipophilic surfactant enhancer and helps to dissolve hydrophobic substances with good solubilizing ability. 46 In addition, it improves permeation 14 and is also listed in the Food and Drug Administration Inactive Ingredients Database.…”

Section: Discussionmentioning

confidence: 99%

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Song

Xie

Hong

et al. 2017

Plastic and Reconstructive Surgery - Global Open

View full text Add to dashboard Cite

Background:We previously showed that intradermal injection of statins is a successful treatment for hypertrophic scarring. Topical application has many advantages over intradermal injection. In this study, we demonstrate the efficacy of topical statin treatment in reducing scar in our validated rabbit ear scar model.Methods:Twenty New Zealand White rabbits were divided into 2 study groups, with 6 rabbits receiving 10 μm pravastatin intradermally at postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10% simvastatin topical application at postoperative days 14–25. Four or 6 full-thickness circular dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. Specimens were collected at 28 days to evaluate the effects of statins on hypertrophic scarring.Results:Treatment with pravastatin intradermal administration significantly reduced scarring in terms of scar elevation index. Topical treatment with both medium- and high-dose simvastatin also significantly reduced scarring. High-dose simvastatin topical treatment showed a major effect in scar reduction but induced side effects of scaling, erythema, and epidermal hyperplasia, which were improved with coapplication of cholesterol. There is a dose response in scar reduction with low-, medium- and high-dose simvastatin topical treatment. High-dose simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA) expression of connective tissue growth factor, consistent with our previously published work on intradermally injected statins. More directly, high-dose simvastatin treatment also significantly reduced the mRNA expression of collagen 1A1.Conclusions:Topical simvastatin significantly reduces scar formation. The mechanism of efficacy for statin treatment through interference with connective tissue growth factor mRNA expression was confirmed.

show abstract

Section: Discussionmentioning

confidence: 99%

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Song

Xie

Hong

et al. 2017

Plastic and Reconstructive Surgery - Global Open

View full text Add to dashboard Cite

show abstract

“…Apart from this there were no differences from controls, for all the parameters measured. A comprehensive review of the non-clinical safety of Transcutol was published by Sullivan et al (2014) Of particular interest is a 6-week oral gavage study in Sprague-Dawley rats which established the low dose of 1340 mg kg -1 day -1 as NOAEL. The intermediate (2680 mg kg -1 day -1 ) and high dose (5360 mg kg -1 day -1 ) groups showed significant treatment effects such as in life (lethargy), haematology and clinical chemistry findings, relative organ weight increases (liver, heart, kidneys) and microscopic changes in the stomach (hyperkeratosis).…”

Section: Discussionmentioning

confidence: 99%

“…The intermediate (2680 mg kg -1 day -1 ) and high dose (5360 mg kg -1 day -1 ) groups showed significant treatment effects such as in life (lethargy), haematology and clinical chemistry findings, relative organ weight increases (liver, heart, kidneys) and microscopic changes in the stomach (hyperkeratosis). Administered in the diet to Wistar rats for 4 weeks, 1.0% transcutol, equivalent to about 800 mg kg -1 day -1 , was established as the NOAEL (Sullivan Jr. et al, 2014). When given for 4 weeks as a mixture with Labrasol and Labrafil, the low-dose level (5 ml kg -1 day -1 containing the equivalent of 1000 mg kg -1 day -1 transcutol) was well tolerated (Delongeas et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Healing

Sulemann

Cotton

et al. 2015

J of Applied Toxicology

View full text Add to dashboard Cite

Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation.

show abstract

“…Transcutol‐HP is an ethylene oxide derivative with chemical name of diethyleneglycol monoethyl ether. Both have been used as detergent and solubilizer for pharmaceutical and cosmetic formulations . Desired transdermal formulation should be site specific and effective.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Skin Permeation of Hydrocortisone Using Nanoemulsion as Potential Vehicle

et al. 2019

View full text Add to dashboard Cite

The current work was performed to estimate the solubility and Hansen solubility parameters of a poorly soluble corticosteroid hydrocortisone (HCN) in various components of nanoemulsion and to enhance the skin permeation rate of HCN using nanoemulsions as potential vehicles. Screening studies suggested the use of Capryol-90 (oil), Triton-X100 (surfactant) and Transcutol-HP (cosurfactant) in the preparation of HCN nanoemulsions. HCN nanoemulsions were developed using low energy emulsification technique and characterized for droplet size, plolydispersity index (PDI), zeta potential (ZP), refractive index (RI), percent of transmittance (% T) and transmission electron microscopy (TEM) and evaluated for drug release behavior. Selected nanoemulsions and control (HCN suspension) were subjected to in vitro skin permeation studies. Optimized formula HSN8 showed droplet size of 52.6 nm, PDI of 0.109, ZP of À 33.72 mV, RI of 1.337 and % T of 97.68%. TEM confirmed spherical-shaped droplets in nanometer range. In vitro drug release evaluation suggested significant release of HCN from optimized nanoemulsion (98.52%) compared with control (35.85%). Skin permeation profile of HCN from optimized nanoemulsion was also significant compared with control. These results suggested the potential of nanoemulsion in enhancing the transdermal delivery of HCN via rat skin.[a] Dr.

show abstract

A review of the nonclinical safety of Transcutol®, a highly purified form of diethylene glycol monoethyl ether (DEGEE) used as a pharmaceutical excipient

Cited by 97 publications

References 21 publications

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Enhanced Skin Permeation of Hydrocortisone Using Nanoemulsion as Potential Vehicle

Contact Info

Product

Resources

About