AIMTo study the effect of lidocaine-dodecanol binary eutectic system on the transdermal permeation of lidocaine.

METHODSBinary eutectic mixture of different proportions of lidocaine and dodecanol were prepared and the patch containing the binary eutectic mixture was developed. The solubilities of pure lidocaine and lidocaine from the binary eutectic system were determined in pH 7.9 phosphate buffer. The transdermal flux of lidocaine from the patches containing the binary eutectic system and pure lidocaine were measured using Franz-type single diffusion cell.

RESULTSThe melting point of the lidocaine-dodecanol binary eutectic system was markedly lower than that of pure lidocaine. The steady state transdermal flux of lidocaine from the patch of the binary eutectic system was six times as much as that of pure lidocaine patch.

CONCLUSIONThe lidocaine-dodecanol binary eutectic system could produce high thermodynamic activity of the drug and the high driving force for transdermal permeation of lidocaine.

Administration, Cutaneous ; Anesthetics, Local ; administration & dosage ; pharmacokinetics ; Animals ; Dodecanol ; administration & dosage ; chemistry ; Drug Combinations ; Drug Stability ; Guinea Pigs ; Lidocaine ; administration & dosage ; pharmacokinetics ; Skin Absorption ; Solubility

No abstract available.
Skin* ; Sodium Dodecyl Sulfate* ; Sodium*

OBJECTIVETo study the effects of different penetration enhancers on the transcutaneous permeability of lappaconitine gel in vitro and therefore to screen out the effective accelerator to enhance the permeation rate of lappaconitine.

METHODUsing improved Franz-type diffusion cell and excised big mouse skin in vitro as transdermal barrier, the kinetics parameters such as cumulative permeation quantity, permeation rate and permeation lagged time were determined by HPLC. The enhancement ability of four different enhancers such as azone (Azone), propylene glycol (PG), oleic acid (OA) and lauryl alcohol (LA), was investigated when used either uniquely or combinatively each other at random.

RESULTWhen used combinatively, Azone + PG, LA + PG, OA + PG can enhance the cumulative permeation quantity, OA + PG was the best one among them.

CONCLUSIONThe selection of the best penetration enhancers provided reference for lappaconitine transdermal delivery.

Aconitine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Administration, Cutaneous ; Analgesics, Non-Narcotic ; administration & dosage ; pharmacokinetics ; Animals ; Azepines ; pharmacology ; Dodecanol ; pharmacology ; Drug Combinations ; Drug Synergism ; Female ; In Vitro Techniques ; Male ; Oleic Acid ; pharmacology ; Propylene Glycol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; drug effects

BACKGROUND: Corrosive irritants can be defined as irritants which in provoked weak reactions or subclinical reactions induce impairment of the water barrier function and increase of transepidermal water loss (TEWL) while non-corrosive irritants can be defined as irritancy of low degree but with no increase of TEWL. Sodium lauryl sulfate (SLS) has been considered as the standard example of corrosive irritant and nonanoic acid (NAA) is an example of a noncorrosive irritant. OBJECT: This study was done to evaluate the skin irritation and recovery by corrosive and non-corrosive irritant in normal human subjects. METHODS: 0.1, 0.2, 0.5, 1, 2, 5% solution of SLS and 1, 2, 5, 10, 20, 50% solution of NAA were applied on volar forearm skin in 15 normal healthy subjects. TEWL and Erythema index (E-index) were measured at before (BL), 30 minutes (D0), 1st day (D1), 2nd day (D2), 1st week (W1), 2nd week (W2), 3rd week (W3) after the removal of the patches. RESULTS: Increase of TEWL was accelerated according to concentrations in cases of SLS, whereas increase of TEWL according to concentrations was very weak in cases of NAA. SLS induced a significantly higher TEWL increase than NAA at corresponding concentrations. In both SLS and NAA, E-index was increased according to concentrations with no difference in reaction pattern. SLS and NAA induced similar degrees of E-index at corresponding concentrations. TEWL value was highest at 30 minutes and 1 day after removal of the patch in both SLS and NAA. TEWL was recovered to baseline value at 2 weeks after removal of the patch test in case of low concentrations, at 3 weeks after removal of the patch in case of high concentrations. E-index value was highest at 30 minutes, 1 day, and 2 days after removal of the patch in both SLS and NAA. The period of recovery to baseline varied depending on the concentrations. E-index was recovered to baseline value at 1 day after removal of the patch test in case of low concentrations, and was not recovered to baseline value after 3 weeks in case of high concentrations. CONCLUSION: Corrosive irritant, SLS, showing similar degree of erythema with non-corrosive irritant, NAA, induced much more damage to stratum corneum barrier function at corresponding concentrations. Skin injuries induced by corrosive irritants would need more prolonged recovery time than skin injuries by non-corrosive irritants, and TEWL measurement would be even more sensitive than E-index measurement in case of corrosive irritants, while both TEWL and E-index measurement could be useful in case of non-corrosive irritants.
Erythema ; Forearm ; Humans ; Irritants* ; Patch Tests ; Skin* ; Sodium Dodecyl Sulfate

Mefenamic acid is a potent analgesic possessing both anti-inflammatory and antipyretic properties. It is completely absorbed one to two hours after intake. Majority of patients however, expect relief of pain within 15 minutes. A new oral mefenamic acid containing sodium lauryl sulfate with a dissolution rate of 98 per cent in 15 minutes has been introduced. This phase 4 clinical trial was conducted to evaluate the onset of pain relief upon administration of mefenamic acid 500 mg combined with sodium lauryl sulfate. The study was an open, noncomparative clinical trial. Physicians all over the Philippines were asked to fill up a standard 3-page case report form. A total of 2,617 patients with a mean age of 36 years were enrolled. Forty two per cent were males and fifty eight per cent were females. Seventy per cent of patients took the drug every 6-8 hours. Majority (78.38%) reported complete resolution of pain (54.3%) of which occurred within 15 minutes, increasing to 84.93% within 30 minutes). Only 1.12 per cent showed no response. Forty one patients (1.57%) reported minor adverse reactions, majority of whose conditions improved with withdrawal of the drug. The overall assessment of clinical response was very good to excellent in 77.66 percent of patients.(Author)

Human ; Male ; Female ; Adult ; Mefenamic Acid ; Antipyretics ; Dodecyl Sulfate ; Sodium Dodecyl Sulfate ; Analgesics ; Pain ; Anti-inflammatory Agents ; Pain Management

Irritant skin reactions can be evaluated by several techniques. Using different scores for the degree of erythema, edema, scaling and fissuring is the time-honored approach but implies t,he disadventagrs of lacking objectivity and pararretric properties. This paper describes the objective nteasurement of irritant. skin responses to various concentrations of Sodium Lauryl Sulfate(SLS) and Ethanol by a color reflectance meter(Chroma Meter) and compares with visual scoring The results are summarized as follows : 1. Pretreatment assessments by a Chroma Meter on normal forearm area showed an average score of 7.70+1.53 for Chroma Meter value a*(rediies:; score). 2. Skin responses to SLS in various concentrations of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 7.5% under occlusion for 24 hours were assessed by visual scoring system. They are measured 0.56+1.10, 0.74+1.29, 1.19 1.36, 2.11+1.69, 2.19+1.91, 2.56+1.50 2.81+2.16 respectively. 3. Skin responses to SLS in various concentrations of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 7.5% under occlusion for 24 hour were assessed by a Chroma Meter valu a*(redness score). They are measured 8.29+1.98, 8.37+2.47, 9.31+2.27, 10.34+2.97, 10.35+3.18, 10.51+2.47, 11.61+3.45 respectively. 4. Skin responses to Ethanol in various concentrations were nearly negligible. 5. We have demonstrated there is a highly significant correlation between skin redness measured by the Chroma Meter and visually assessed erypthma(p<0.0001). It yields reproducible, objective, quantitative measurements of iryhema that parallel the subjective visual assessments.
Edema ; Erythema* ; Ethanol* ; Forearm ; Humans ; Male ; Skin* ; Sodium Dodecyl Sulfate* ; Sodium*

Five volunteers received patch tests with 5% sodium lauryl sulfate (SIS) in solutions of differing pH. The irritant effect was monitored by visual scoring as well as by a laser Doppler vlelocimeter, evaporimeter, cutometer, and colorimeter. The non-invasive methods used in this study with the exception of the cutometer were effective in the evaluation of skin irritation. No significant differences in the skin responses to SIS in different pH solutions were found either clinically or by the non-invasive methods used for quantification. It was concluded that the pH of SIS is not a major factor in the degree of skin irritation produced by SIS.
Hydrogen-Ion Concentration* ; Patch Tests ; Skin ; Sodium Dodecyl Sulfate* ; Sodium* ; Volunteers

BACKGROUND: The main function of the stratum corneum is to serve as a barrier preventing the penetration of irritants and transepidermal water loss (TEWL). Previous studies have shown that the cutaneous barrier disruption by application of acetone or sodium lauryl sulfate (SLS) and tape stripping leads to various metabolic changes. Recent studies showed that there was some difference in the recovery rate between tape-stripped groups and acetone-treated groups, and an individual irritant not only exerted rather specific morphologic effects on the cellular components of the keratinocyte but also induced distinct morphological alterations of the different components of the stratum corneum. In other words, this data suggested that individual irritants could show different cutaneous barrier recoveries. OBJECTIVE: This study was done to compare the recovery rate after cutaneous barrier disruption between a tape-stripped group and a SLS irritated group, and to test the relationship among baseline TEWL, TEWL after the SLS irritation, recovery of TEWL, and number of strippings needed to increase TEWL up to 20g/m2/h. METHODS: The permeability barrier of normal human skin was disrupted by tape stripping and patch of SLS and the recovery rate was assessed by measure of TEWL and erythema (E-) index. RESULTS: The number of tape strippings needed to increase TEWL up to 20g/m2/h was 32.7+-9.6 (20-50). The recovery rate of TEWL was 56.85+-17.97% twenty-four hours after tape stripping and 51.55+/-24.73% after patch removal, and 82.70+/-8.70% and 76.61+/-11.14% four days after tape stripping and patch removal. There was no significant difference in the recovery rate of TEWL after the two methods of epidermal barrier perturbation. All the correlations among baseline TEWL, TEWL after the SLS irritation, recovery of TEWL, and number of strippings were not significant statistically. E-index after the tape stripping was 12.07+/-2.95 and higher than that after removal of SLS, 11.20+/-2.51. There was irregular recovery of E-index in the SLS irritated group, but not irregular in the tape-stripped group. There was no significant difference in the recovery rate between the two groups. CONCLUSION:There was no significant difference in the recovery rates of TEWL and E-index between the tape-stripped group and the SLS irritated group. We suggest that TEWL measurements may be more desirable than the measurement of E-index in the study of perturbation and recovery of the skin barrier function.
Acetone ; Erythema ; Humans ; Irritants ; Keratinocytes ; Permeability ; Skin* ; Sodium Dodecyl Sulfate* ; Sodium*

BACKGROUND: Sodium lauryl sulfate(SLS) is the most widely utilized model for studying acute and cumulative irritation. Sodium lauroyl glutamate(SLG) has exhibited a low irritation potential and an anti-irritating effect on other anionic surfactants. OBJECTIVE: Our study was done to compare the skin irritancy of SLS and SLG using non-in- vasive techniques. METHODS: Patches with 1% SLS and SLG solution were applied to the volar forearm of 20 healthy volunteers for 24 h. Finn chambers with 8mm(20pl) and 12mm(60pl) inner diameters were used. Visual scores, transepidermal water loss(TEWL) and an erythema(E)-index were measured at 30 min after removal of the patches, and every 24hours(h) up to 4 days. RESULTS: The results are summarized as follows. 1. Visual scores were 0.20+0.30(8mm) and 0.73+0.34(12mm) at 24 h after removal of 1% SLS and were 0.15+0.29(8mm) and 0.30+0.41(12mm) at 24 h after removal of 1% SLG. They were increased at 30 min and 24 h after removal and decreased towards normal at 4 days after removal. By chamber size, the skin response with large Firin chamber(12mm) increased more significantly than with the small Finn chamber(8mm). In the small Finn chamber, there were no significant differences in the skin response between 1% SLS and 1% SLG. In the large Finn chamber, the skin response with 1% SLS increased more significantly than with 1% SLG. 2. TEWL values were 11.14+4.77(8mm) and 20.48+10.61(12mm) at 24 h after removal of 1 % SLS and were 10.38+3.99 and 14.87+7.46 at 24 h after removal of 1% SLG. They were increased at 30 min after removal and decreased towards normal 4 days after removal. By chamber size, their results were the same as the visual scores. Also, on comparison between 1% SLS and 1% SLG, their results were the same as the visual scores. 3. E-index was 10.05+2.70(8mm) and 11.15+2.56(12mm) at 24 h after removal of 1% SLS and was 10.15+2.16 and 10.60+2.26 at 24 h after removal of 1% SLG. They were increased at 30 min after removal and decreased towards normal 4 days after removal. By chamber size, their results were the same as the visual scores. In the small and large Finn chamber, there were no significant differences in the skin response between 1% SLS and 1% SLG. CONCLUSION: SLS is more irritating than SLG. The large Finn chamber may be more suitable to yield positive irritant reactions than the small Finn chamber. Also, TEWL measurements may be a more accurate and sensitive method than the E-index.
Forearm ; Glutamic Acid* ; Healthy Volunteers ; Skin ; Sodium Dodecyl Sulfate* ; Sodium* ; Surface-Active Agents

BACKGROUND: With the development of bioengineering techniques for noninvasive characterization of skin pathophysiology, the induction of irritant dermatitis by surfactants has been extensively studied. OBJECTIVE: We performed this study to compare the skin responses in terms of transepidermal water loss (TEWL) and erythema induced by benzalkonium chloride (BAC), a well-known non-corrosive irritant, in comparison with sodium lauryl sulfate (SLS), a representative corrosive irritant. METHOD: We applied 0.1, 0.2, 0.5, 1, and 2% solutions of BAC and SLS on volar forearm skin for 24 hours using a large Finn chamber with filter paper disc on 19 normal healthy subjects. TEWL and erythema index (E-index) were measured prior to testing, then at 30 minutes, one day, two days, three days, one week, and two weeks after the removal of the patches. RESULTS: TEWL values of BAC and SLS patch areas increased with concentration. However, BAC induced a significantly lower TEWL increase than SLS did at the corresponding concentrations. TEWL induced by BAC was highest at 30 minutes after the removal of the patch, whereas TEWL induced by SLS was highest at one day. TEWL values had recovered with the passage of time to baseline values at 2 weeks after removal of the patch at lower concentrations (0.1, 0.2, 0.5%) of SLS, but still showed significantly high TEWL values at 1% and 2% concentration SLS patch areas. TEWL values of BAC in 0.1, 0.2, 0.5 and 1% concentrations had recovered to the baseline values at 2 weeks after the removal of the patch, but not in 2% concentration BAC patch areas. E-indices of BAC and SLS increased with concentration in a similar reaction pattern. E-index induced by BAC was highest at 30 minutes after the removal of the patch, and E-index induced by SLS was highest at 30 minutes or 1 day after the removal of the patch. E-index of each concentration, except 2%, had recovered with the passage of time to baseline values on both BAC and SLS patch areas at 2 weeks, but E-indices of both 2% BAC and SLS did not recover at 2 weeks. CONCLUSION: Benzalkonium chloride showed much less damage to the skin barrier function compared to the corresponding concentration of SLS, whilst they showed a similar degree of erythema. Skin barrier function affected by the corrosive irritant SLS would need a more prolonged recovery time than skin barrier disruption by non-corrosive irritant BAC.
Benzalkonium Compounds* ; Bioengineering ; Dermatitis, Irritant ; Erythema ; Forearm ; Skin* ; Sodium Dodecyl Sulfate* ; Sodium* ; Surface-Active Agents