Low Irritation Research Articles

Spinal stabilization–an update. Part 2—functional assessment

Reactivating spine pain patients is a key to early recovery from acute and subacute episodes ( Malmivaara et al (1995) Malmivaara A Hakkinen U Aro T et al. The treatment of acute low back pain—bed rest, exercises, or ordinary activity?. New England Journal of Medicine. 1995; 332: 351-355 Crossref PubMed Scopus (559) Google Scholar ; Indahl et al (1998) Indahl A Haldorsen E.H Holm S Reikeras O Hursin H Five-year follow-up study of a controlled clinical trial using light mobilization and an informative approach to low back pain. Spine. 1998; 23: 2625-2630 Crossref PubMed Scopus (171) Google Scholar ), prevention of recurrences ( Hides et al (2001) Hides J.A Jull G.A Richardson C.A Long-term effects of specific stabilizing exercises for first-episode low back pain. Spine. 2001; 26: e243-e248 Crossref PubMed Scopus (635) Google Scholar ), and treatment of chronic pain, disability, and failed surgery syndrome ( Fordyce et al (1986) Fordyce W.E Brochway J.A Bergman J.A et al. Acute back pain a control-group comparison of behavioral vs. traditional management methods. Journal of Behavioral Medicine. 1986; 9: 127 Crossref PubMed Scopus (153) Google Scholar ; Lindstrom et al (1992) Lindstrom A Ohlund C Eek C et al. Activation of subacute low back patients. Physical Therapy. 1992; 4: 279-293 Crossref Scopus (427) Google Scholar ; Manniche et al (1991) Manniche C Lundberg E Christensen I Bentzen L Hesselesoe G et al. Intensive dynamic back exercises for chronic low back pain. Pain. 1991; 47: 53-63 Abstract Full Text PDF PubMed Scopus (187) Google Scholar ; O’Sullivan et al (1997) O’Sullivan P Twomey L Allison G Evaluation of specific stabilizing exercise in the treatment of chronic low back pain with radiologic diagnosis of spondylolysis or spondylolysthesis. Spine. 1997; 24: 2959-2967 Crossref Scopus (827) Google Scholar ; Timm (1994) Timm K.E A randomized-control study of active and passive treatments for chronic low back pain following L5 laminectomy. JOSPT. 1994; 20: 276-286 Crossref PubMed Scopus (95) Google Scholar ). The first part of this series described the role of instability in low back problems (LBP) as well as specific types of biomechanical advise to prevent low back irritation. This second part will describe the patient's functional assessment. Functional assessment is necessary to establish goals, monitor progress towards those goals, and guide the prescription of specific exercises.

Amino acid-based surfactants

There is a pressing need for developing efficiently surfactants that are biodegradable and biocompatible. Surfactant molecules from renewable raw materials that mimic natural lipoamino acids are one of the preferred choices for food, pharmaceutical and cosmetic applications. Given their natural and simple structure they show low toxicity and quick biodegradation. The value of amino acids and vegetable oil derivatives as raw materials for the preparation of surfactants was recognized as soon as they were discovered early in the last century. The combination of polar amino acids/peptides (hydrophilic moiety) and non-polar long-chain compounds (hydrophobic moiety) for building up the amphiphilic structure has produced molecules with high surface activity. Our group has a wide experience in synthesis (chemical, enzymatic or, usually, by a combination of both methodologies) of amino acid-based surfactants obtained from the combination of natural saturated fatty acids, alcohols and amines with different amino acid head groups through ester and amide linkages. Thus, saturated single-chain, double-chain, and gemini surfactants of different ionic character have been found to be in all cases highly biodegradable, with low toxicity, ecotoxicity and irritation effects. Water solubility and self-aggregation properties were directly associated with the chemical structure of the molecule and only cationic lipoamino acids possessed antimicrobial activity. To cite this article: M.R. Infante et al., C. R. Chimie 7 (2004) .

FC04.1 Some new and unexpected allergens in cosmetics

Labels on cosmetics with statements such as ‘recommended by dermatologists’, ‘allergy‐tested’, ‘hypo‐allergenic’, and more recently ‘for use on intolerant’ or for ‘sensitive skin’ have become very popular. Indeed, many ingredients are used precisely because of their low irritancy potential. However, this does not preclude the occurrence of contact allergic reactions from such cosmetic products. During the last few months several of these substances have been identified as allergens. Examples are: – Alkylglucosides, e.g. coco‐, decyl‐, and laurylglucosides, which are condensation products of the corresponding fatty alcohols with glucose, are widely used as emulsifiers in skin‐care products, mild surfactants and cleansing agents, as well as in fragrance products, hair dyes, sunscreens and tanning products. – Ethylhexylglycerin (syn.: octoxyglycerin) is used as a skin conditioning agent (and for miscellaneous purposes). – Methoxy PEG‐17 and PEG‐22/dodecyl glycol copolymers, which are alkoxylated alcohols and synthetic polymers, are used as emulsion stabilizers and suspending and viscosity‐increasing agents, and also as skin‐conditioning agents. – Butylene glycol and pentylene glycol are aliphatic alcohols with applications similar to those of propylene glycol, which is considered to be more irritant and allergenic. These agents are widely used in a wide variety of cosmetic products because of their solvent, humectant and antibacterial effects. Butylene glycol is also usd as a fragrance ingredient and as a skin conditioner.

Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents

This randomized, investigator-blinded study evaluated the level of skin tolerance to adapalene gel 0.1%, tretinoin cream 0.025%, or tretinoin microsphere gel 0.1% when applied in combination with clindamycin phosphate lotion 1%, erythromycin gel 2%, benzoyl peroxide gel 5%, or erythromycin-benzoyl peroxide gel. A total of 37 subjects underwent daily application of the topical antimicrobial and retinoid products to sites on their upper back under protective patches for approximately 16 hours each day; Friday patches were left in place over the weekend. Testing continued daily for 3 weeks or until discontinuation caused by a severe adverse reaction to any of the test products or to the patch. Adapalene gel 0.1% demonstrated statistically significantly ( P < .001) less irritation after repeated application under occlusive conditions than tretinoin cream 0.025% or tretinoin microsphere gel 0.1%. Moreover, the application of adapalene gel 0.1% under these conditions, concomitantly with various antimicrobial agents, was safe and well tolerated in this subject population. In view of its low irritation potential and its efficacy, adapalene gel 0.1%, in combination with antimicrobial agents should be considered for the treatment of acne vulgaris.

Novel transdermal drug penetration enhancer: synthesis and enhancing effect of alkyldisiloxane compounds containing glucopyranosyl group

The syntheses of alkyldisiloxanes containing sugar moiety with various alkyl chain length were investigated, in order to develop a silicone-based transdermal penetration enhancer which was expected to show a low irritation to the skin. 1-Alkyl-3-β-d-glucopyranosyl-1,1,3,3-tetramethyldisiloxanes (Glc–SiCs) were prepared by two-step hydrosilylations of 1-alkene and 1-allyl-β-d-glucose tetraacetate with 1,1,3,3-tetramethyldisiloxane in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect of Glc–SiCs on the percutaneous drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine (ANP) and indomethacin (IND) were used as hydrophilic and hydrophobic model drugs, respectively, and the amount of drug permeating through the rat abdominal skin with or without Glc–SiCs was estimated by HPLC. As a result, Glc–SiCs exhibited a enhancing effect on the permeation of both drugs through the skin, which was influenced by the alkyl chain length of Glc–SiCs. In addition, it was suggested that a suitable balance of polarity would be necessary to appear the high enhancing effect, where Glc–SiCs with octyl and decyl groups exhibited the highest enhancing effect. From the determination of kinetic parameters in the drug permeation, it was also found that this enhancing effect was due to the increase of both partition and diffusion coefficients of drug permeation through the skin. By experiments to determine the amount of cholesterol extracted from the skin, the defatting effect would be one of the functions of Glc–SiCs which resulted in the high enhancing activity. Furthermore, according to the Draize test, it was confirmed that Glc–SiCs showed a low irritation to the skin.

Evaluation of the cytotoxicity of calcium phosphate root canal sealers

Complete obturation of the root canal with an inert filling material and creation of a hermetic apical seal have been proposed as goals for successful endodontic treatment. Currently, the methods most frequently used in filling root canals involve the use of core points, such as gutta-percha, inserted in conjunction with sealers or pastes. Many types of root canal sealers using zinc oxide-eugenol, resins, calcium hydroxide, glass ionomer, calcium phosphate and so on have been commercially available and clinically used. Since these materials will be in direct contact with periapical tissues for a long period of time, their biocompatibility is important. It is well known that calcium phosphate biomaterials show high stability and low irritation to tissues, but it does not set itself by any chemical reaction. Thus, it might be unsuitable for use as a major component of a root canal sealer. On the other hand, according to Brown and Chow, a cerEvaluation of the Cytotoxicity of Calcium Phosphate Root Canal Sealers

Developments in topical retinoid therapy for acne.

Topical retinoic acid was introduced for acne treatment three decades ago. Since that time, researchers have discovered thousands of retinoids, originally defined as chemical analogs of vitamin A. After the identification of nuclear retinoid receptors in 1987, the definition of this class expanded to include molecules that bind to and activate such receptors. The receptor-selective retinoid agents, adapalene and tazarotene, were developed in the 1990s. Other innovations of the past decade include retinoid formulations and methods aimed at limiting retinoid absorption. Cutaneous irritation may be reduced without losing retinoid efficacy by inhibiting retinoid penetration into the deep epidermis and dermis. Examples include tretinoin in slow-release vehicles and the short-contact method of tazarotene gel therapy. Only trace amounts of adapalene are absorbed after topical application, perhaps explaining its relatively low irritancy. New formulations of existing agents, such as additional concentrations of tretinoin in microsphere gel and cream formulations of tazarotene, are now under investigation for acne. Current research focused on receptor selectivity holds the promise of yielding new retinoid molecules with improved benefits and safety.

Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel

Background: Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. Objective: This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). Methods: This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for ∼24 hours; the Friday patches were left in place over the weekend for ∼72 hours. Results: All 36 subjects (26 men, 10 women; age, 18–49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had ≥1 application discontinued prematurely on ≥1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25–1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products ( P < 0.01). Conclusions: Adapalene gel and cream were well tolerated, with possible benefits for compliance. Their low irritation potential should be considered when prescribing a topical retinoid for the treatment of acne vulgaris.

NMR characterisation and transdermal drug delivery potential of microemulsion systems

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T 1 relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.

The Rate of Ozone Uptake on Carpets: Experimental Studies

Ozone can react with surfaces, reducing indoor concentrations. Carpets may be important ozone sinks because of their high surface area. We conducted laboratory experiments to measure ozone uptake on four samples of whole carpet and on the corresponding carpet fibers and carpet backing. Results were parametrized in terms of reaction probability, defined as the rate of ozone loss on a surface normalized by the rate of ozone-surface collisions. For whole carpet and carpet-backing samples, we found the apparent reaction probability to be of magnitude 10-5 to 10-4. These results are referenced to the floor area that would be covered by the carpet, rather than to the total surface area of the carpet and its fibers. Reaction probabilities of the order of 10-7 to 10-6 were measured on carpet fibers, referenced to total estimated fiber area. The results indicate that carpet is of comparable significance to painted walls in scavenging ozone from indoor air. All samples tested exhibited aging, such that the rate of ozone uptake diminished with increasing cumulative exposure. Although reactions on carpeting can reduce human exposure to ozone, we caution that the reaction products may include volatile carbonyls that have low odor or irritation thresholds.

Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs)

The popular view that all nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the production of prostaglandins has been challenged by the discovery that they also affect a wide variety of cellular processes that are important for their therapeutic actions and side effects. Although recognition of the differential activities of new and established NSAIDs on the activities of the cyclooxygenases (COXs) affecting production of inflammatory prostaglandins (from COX-2) and those that are physiologically important (from COX-1) may have significance for the prostaglandin components of the underlying inflammatory and physiologic processes, there are important features of their chemical structures that determine the various cellular and biochemical actions of these agents. Several established NSAIDs have low propensity to cause gastrointestinal (GI) ulceration and bleeding that may relate to these drugs having unique pharmacokinetic characteristics (pro-drugs, protein binding, etc). They also have weak effects on the production of GI mucosal prostaglandins and have specific physicochemical characteristics such that they cause minimal damage to mucosal membranes or effects on nonprostaglandin-related cellular mechanisms important in mucosal defenses. Some of the new COX-2–selective drugs with methyl or amino-sulfonyl moieties have relatively high pKa values and other properties that are similar to established NSAIDs with low GI ulcerogenicity. These physicochemical properties may contribute to the low irritancy of the new COX-2–selective drugs quite apart from their sparing of COX-1 in the GI mucosa. With concerns that some established NSAIDs may accelerate cartilage destruction in osteoarthritis (OA), interest is now focusing on whether the COX-2–selective drugs may have a lower potential for this adverse effect by avoiding the inhibitory effects on cartilage proteoglycan metabolism seen with such drugs as indomethacin and the salicylates. Meloxicam appears to be without inhibitory effects on proteoglycan metabolism, but it remains to be seen if this translates into any beneficial actions on the progression of joint changes in OA observed radiologically or from magnetic resonance imaging.

Pharmaceutical properties of fluticasone propionate nasal drops: a new formulation.

A variety of corticosteroid delivery systems have been considered for the treatment of nasal polyposis. Safety considerations favour local delivery of the drug to the nasal cavity. No topical delivery system is entirely without problems, however, and formulations must address issues of microbiological quality, drug stability, reproducible drug delivery and adequate drug distribution at site, while also offering environmental and patient acceptability. Fluticasone propionate has been formulated in a new nasal drop preparation. As a highly water-insoluble compound, the active fluticasone propionate requires micronization to an optimal particle size and subsequent dispersion with a surface-active wetting agent. The product is presented in a unit dose low-density polyethylene container, manufactured by a blow-fill-seal process and stored in an aluminium foil overwrap. Micronized active has been used to promote optimal local drug delivery, and excipients have been selected for low irritancy potential and high formulation stability. There is no microbiological risk with fluticasone propionate unit dose nasal drops 400 microg and therefore no need to include a preservative in the preparation. They provide a convenient and effective treatment option for patients with nasal polyposis.

Clearning performance and foaming properties of lauroylamidopropylbetaine/nonionics mixed systems

AbstractLauroylamidopropylbetaine (LPB) has good cleaning and foaming performance with excellent low skin irritation. We have investigated the relationship between cleaning performance and foaming properties of aqueous solutions containing binary and ternary LPB/nonionic surfactant systems. Foaming properties were evaluated by observing dynamic surface tension and aqueous core thickness of a vertical foam film measured by Fourier transform infrared spectroscopy. The LPB/lauroyldiethanolamide (LDE) system has a positive synergistic effect on cleaning performance and foam stability, estimated from the grease removal test and dishwashing test for a light‐duty detergent. However, this system shows very poor initial foam performance in both the sponge test and Ross‐Miles foam test. This disadvantage of the LPB/LDE system was improved using C12En (polyoxyethylene dodecyl ethers). Addition of C12En promoted dynamic surface tension lowering, indicating an improvement in the initial foaming performance, while maintaining cleaning performance and foam durability. Thus, the LPB/LDE/C12En ternary system has an excellent cleaning and foam performance as a light‐duty liquid detergent.

Comparing and evaluating alternative ( in vitro) tests on their ability to predict the Draize maximum average score

The Cosmetic, Toiletry, and Fragrance Association (CTFA) Evaluation of Alternatives Program comprised a multi-phased study of the relationship between Draize eye irritation test data and comparable data from a selection of promising alternative ( in vitro) tests. The CTFA Program was designed to determine the effectiveness and limitations of several in vitro tests over a range of different cosmetic and personal-care product types. Test materials constituted experimental formulations representative of three distinct product types. Each material was tested in vivo (according to a modified Draize eye irritation test protocol) and in vitro (according to one of up to forty different protocols). A statistical ranking and selection procedure (“concordance analysis”) was used to identify those in vitro tests where the relationships between in vitro and in vivo score was sufficiently well defined to warrant further statistical analysis. In vitro test performance was then evaluated by regression modelling of these relationships. Maximum average Draize score (MAS) was utilized as the primary quantitative measure of eye irritation potential in vivo. The goodness-of-fit of the observed data to the regression model and comparison of the magnitude of upper and lower prediction-bounds on the range of probable MAS values associated with the regression model fit (prediction intervals) provide a means by which the performance of each in vitro test may be measured relative to Draize test outcome. The narrower the prediction interval (i.e. the more precise the fit), the more predictive of in vivo score (MAS) is the in vitro test result. The prediction interval thus represents uncertainty associated with Draize test prediction. Such uncertainty depends heavily on the degree of irritancy. In Phases I and II, the widths of the prediction intervals were narrowest in the region corresponding to low irritation potential; increasing widths were observed as irritation potential increased. In Phase III, relatively narrow prediction interval widths were observed at both the low and high end of the observed range of irritation potential; wider intervals were observed in the middle of the observed range. In general, the selected endpoints in each phase had similar average prediction interval widths and thereby differed only slightly in their ability to predict MAS to a given level of precision; any differences between endpoints tended to occur at the low and/or high ends of the observed range of irritation potential. The primary contributor to total variability associated with prediction of MAS is the deviation between the Draize score as observed in the laboratory and what is predicted by the model for a given formulation. Consistently, this component is responsible for 70% to 95% of the total variability. The other components (i.e. variability among replicate MAS and in vitro scores) could be reduced simply by increasing the number of replicate tests performed on each test formulation. However, this would have relatively little impact on the overall precision of prediction.

Tolerance Profile of Retinol, Retinaldehyde and Retinoic Acid under Maximized and Long-Term Clinical Conditions

Background: Topical retinoic acid (RA) causes irritation of the skin. To prevent this side effect, natural precursors of RA have been proposed. The aim of the present study was to compare the local tolerance profiles of retinol (ROL), retinaldehyde (RAL) and RA. Methods: ROL, RAL and RA were studied using repeated insult patch tests for 14 days (n = 6). Similarly, RAL and RA were assessed in long-term clinical use for 44 weeks (n = 355). Clinical scoring on irritation, measurement of transepidermal water loss (barrier function) and laser Doppler blood flow perfusion units (irritation) were performed. Results: Under maximized conditions, an equally low irritation potential for ROL and RAL and a more pronounced irritant effect with RA could be demonstrated clinically (p < 0.05 in the intergroup analysis). Furthermore, RAL and RA induced more scaling than ROL (p < 0.05), and ROL and RA tended to induce more burning/pruritus than RAL (nonsignificant). The TEWL values were low with ROL and high with RAL and RA (nonsignificant, intergroup analysis). The laser Doppler measurements confirmed pro-irritating effects of RA and the nonirritating effects of ROL and RAL (p = 0.001, intergroup analysis). The long-term clinical study showed that the study population developed a high frequency of erythema (44% of the population), scaling (35%) and burning/pruritus (29%) with RA in the first 4 weeks of treatment, whereas these 3 parameters were significantly less frequent with RAL (p < 0.0001 in the intergroup analysis). Conclusion: The natural retinoids ROL and RAL do have a good tolerance profile, in contrast with the irritating potential of RA.

Evaluating the Potential Occupational Hazard of Handling Dental Polymer Products Using the HET-CAM Technique

The irritation potencies of 8 dental polymer products, used as dental restorative materials, adhesives, or temporary constructions, were tested using the HET-CAM (hen’s egg test-chorioallantoic membrane) technique. Liquid and powder components, and extracts of cured and freshly mixed non-cured materials of 5 glass ionomers, 1 bonding, 1 composite, and 1 cold-cured acrylate were examined. Results showed that the liquid component of all products had a strong irritation capacity but powder suspensions and extracts from cured and freshly mixed non-cured materials had no effect on the CAM. Thus, dental personnel who handle liquid and powder manually are exposed to components with a high irritation potential, in contrast to patients who are exposed to the cured and mixed non-cured materials with low irritation potential. This illustrates the importance of safe handling procedures and practices for dental personnel who handle non-cured polymers manually.

Adapalene 0.1% gel has low skin irritation potential even when applied immediately after washing

The efficacy and tolerability of tazarotene 0.1% gel in the treatment of acne vulgaris have been compared with those of tretinoin 0.025% gel and adapalene 0.1% gel in multicenter, double-blind, randomized, parallel-group trials. Preliminary results from the tazarotene versus tretinoin trial suggest that once-daily tazarotene is more efficacious than once-daily tretinoin in reducing the numbers of papules and open comedones, and achieves a more rapid reduction in pustules. Both drugs appear to be equally efficacious against closed comedones. Preliminary results from the tazarotene versus adapalene trial suggest that, when tazarotene is applied only half as frequently as adapalene (every other day versus every day), the two drugs achieve comparable reductions in noninflammatory and inflammatory lesion counts. The results from these studies, and a separate split-face tolerability study, suggest that the tolerability of tazarotene gel is clinically comparable to that of tretinoin 0.025% gel, tretinoin 0.1% gel microsphere, and adapalene 0.1% gel. (J Am Acad Dermatol 2000;43:S51-4.)

Adapalene 0.1% gel has low skin irritation potential

Adapalene 0.1% gel has low skin irritation potential

Effect of Cod-Liver Oil Extract on the Buccal Permeation of Ergotamine Tartrate

Ergotamine tartrate (ET) is used clinically in the treatment of migraines. However, the bioavailability of ET is rather poor following oral administration. Therefore, we tried to improve ET delivery using buccal administration. The purpose of this study was to investigate the characteristics of the permeation of ET through the hamster cheek pouch in vitro using a two-chamber diffusion cell, and to evaluate the effect of permeation enhancers on the transbuccal delivery of ET.Cod-liver oil extract (CLOE), polyoxyethylene hydrogenated castor oil (HCO 60), sodium glycocholate (GC), and sodium caprate (CA) were selected as permeation enhancers considering their low irritancy of the mucosa. When the enhancers were added to the donor cell at a 5% concentration each, the ET permeation rate markedly increased compared with that in a control not containing enhancer. Among these enhancers, CLOE exhibited the greatest effect.Because CLOE is composed of 16 kinds of fatty acids, the enhancement action of each of the major components was separately determined. As major fatty acids, palmitic acid, oleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were selected and their enhancing effects were studied. The enhancing effect of each fatty acid was significantly lower than that of CLOE.

Conformability and irritancy of adhesive tapes on the skin.

The relationship between the conformability of adhesive tape, the mechanical property of the adhesive tape not to interfere with skin movement, and irritation of the skin was investigated. In order to assess the conformability of adhesive tape to the skin, a uniaxial method employing film strips connected to a strain gauge was used to measure the elastic property of the skin, with or without application of various elastic tapes. The tension loaded on the strain gauge was measured while the skin was extended by 15% of its original length in a direction across the humeral axis on the flexor side of the upper right arm. The most elastic adhesive tape showed the best conformity to the skin. The same adhesive tapes were applied on the flexor side of both upper arms so that the tape held a piece of sanitary cotton in place for 24 h. Dermal irritation was not so remarkable in the skin under the inner part of the tapes. On the other hand, the skin reaction was much more severe on the skin under the edge portion of the applied tape which showed poor conformability to the skin. These findings seemed to indicate that the skin reaction was caused by localized distortion of the skin under the edge portion of the applied tapes, during movement of the underlying muscle. Actually, the distortion of the skin surface was great in the areas immediately outside the edge of the applied tape. In conclusion, adhesive tape conformable to skin movement reduced localized distortion of the skin during application, resulting in low irritation at the edge of the applied tape.