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[The influence of transdermal nitroglycerin patches on fetal blood flow parameters in threatened preterm labor].

OBJECTIVES: The aim of our study was the assessment of fetal arterial Doppler parameters (umbilical artery and middle cerebral artery) in threatened preterm labor in the course of transdermal nitroglycerin therapy. MATERIALS AND METHODS: 16 pregnant women in between 27th and 34th week of gestation with symptoms of threatening preterm labor were brought into our study. Patients were treated with transdermal nitroglycerin (5 mg) patches. Maternal blood pressure. Manning's test score and fetal arterial Doppler blood flow were measured. RESULTS: Whereas maternal systolic blood pressure does not vary in the course of therapy, significant decrease in diastolic blood pressure was noted. There was no change in the mean umbilical and middle cerebral artery blood flow in the course of treatment. CONCLUSIONS: Nitroglycerin in the form of transdermal therapeutic system releasing nitric oxide doesn't effect fetal artery Doppler parameters. Nitroglycerin may be used as a safe therapeutic agent in treatment of preterm labor.

Administration, Cutaneous↗

Prospective, randomised study with three HRT regimens in postmenopausal women with an intact uterus.

OBJECTIVE: To compare compliance, symptom control, bleeding patterns, lipid and biochemical changes in postmenopausal women treated with three regimens of HRT. METHODS: In a prospective, randomised, group comparative study, with 165 patients, the effects on the aforementioned parameters, as well as treatment compliance and side effects were studied with oral tibolone 2.5 mg per day, with cyclic combined regimen of transdermal oestrogen and progestogen (transdermal patch of 17beta-oestradiol 50 microg/day during 14 days and transdermal patch of 17beta-oestradiol 50 microg/day plus 0.25 mg/day NETA during the following 14 days), and with intermittent progesterone regimen (transdermal 17beta-oestradiol 50 microg/day and oral micronised natural progesterone 200 mg twice a week). Statistical analysis was carried out using the Fisher-test, analysis of the variance (ANOVA) and the Bouferoni test. RESULTS: Ten women dropped out of the tibolone group, 11 dropped out of the intermittent dosing group and 21 dropped out of the cyclid combined group. Irregular bleeding occurred at more rates in the cyclid combined group. Similar reductions in climacteric symptoms were found in the three groups. No differences were observed with respect to biochemical analysis. CONCLUSIONS: Efficacy and safety of the three treatment regimens being comparable, but the patients in our study preferred those that did not produce bleeding episodes.

Administration, Cutaneous↗

A comparison of transdermal and oral HRT for menopausal symptom control.

BACKGROUND: To compare clinical efficacy, side effects and continuation rates using oral hormone therapy (HT), percutaneous gel, and transdermal patch. METHODS: Eighty-eight symptomatic menopausal women were allocated into 3 groups (oral, gel, patch); the patch group was further subdivided to be given either reservoir or matrix patch. After one year of follow up, symptomatic improvement, side effects and continuation rates were assessed and compared. Statistical analysis was performed using multiple analysis of variants and chi-square tests wherever appropriate, with p value < or = 0.05 considered significant. RESULTS: Percentage of patients showing complete relief from vasomotor symptoms at one year were 62%, 95%, and 100% among oral, gel, and patch groups, respectively. Similarly, above-mentioned percentages were 30%, 65%, and 68% for psychological disturbances; 64%, 100%, and 100% for genital symptoms; 40%, 90%, and 100% for urinary symptoms. Incidence of side effects, such as breakthrough bleeding [6 (60%), 6 (71%), and 5 (66%) among oral, gel, and patch groups at 6 months] and mastodynia [5 (14%), 6 (20%), and 5 (18%)] was comparable among three groups. Skin intolerance was significantly higher (92% of patients) in the reservoir patch group compared to the matrix patch (22% of patients) and gel (10% of patients) at first month. Continuation rate for one year was comparable among oral, gel, and matrix patch: 81%, 83%, and 88%, respectively. However, continuation rate was 50% among reservoir patch group. CONCLUSION: Transdermal HT performed significantly better than oral HT in menopausal symptom control. Reservoir patch was unsuitable in tropical climate where matrix patch and gel performed better.

Administration, Cutaneous↗

Transdermal ethinylestradiol/norelgestromin: a review of its use in hormonal contraception.

UNLABELLED: Ethinylestradiol 20 microg/day plus norelgestromin 150 microg/day have been formulated into a transdermal patch for hormonal contraception. The predominant mechanism of action for transdermal ethinylestradiol/norelgestromin (Ortho Evra, Evra) is inhibition of ovulation by suppression of gonadotropins. It suppresses follicular development, induces changes to the endometrium that reduce the probability of implantation, and increases the viscosity of cervical mucus, which may prevent sperm penetration into the uterus. Two large randomized, nonblind efficacy studies demonstrated that transdermal ethinylestradiol/norelgestromin was as efficacious in preventing pregnancy as oral triphasic ethinylestradiol/levonorgestrel or oral ethinylestradiol/desogestrel. A large, noncomparative study also showed transdermal ethinylestradiol/norelgestromin to have good contraceptive efficacy. Moreover, in the two comparative trials, women using transdermal ethinylestradiol/norelgestromin had higher rates of perfect compliance than women using oral contraception. Age did not affect the rate of perfect compliance in women using the transdermal ethinylestradiol/norelgestromin patch, whereas the rate of compliance reduced with younger age in oral contraceptive users. Pooled results from three efficacy studies found that 1.8% of patches were replaced as a result of complete detachment and 2.9% because of partial detachment. Physical exercise, water immersion, and living in a humid climate did not affect patch adhesion. Transdermal ethinylestradiol/norelgestromin was generally well tolerated in clinical trials. The most common menstrual disturbances were breakthrough bleeding/spotting and dysmenorrhea. The incidence of discontinuation of treatment because of an adverse event was < or = 3.2%, with the most common reason being application-site reactions. CONCLUSIONS: Transdermal ethinylestradiol/norelgestromin offers a well tolerated, effective, reversible, and easy-to-use method of hormonal contraception with an increased likelihood of compliance relative to oral contraceptives.

Administration, Cutaneous↗

Comparative acceptance of three transdermal nitroglycerin placebo patches.

Factors that might affect patient acceptance of transdermal drug-delivery system patches were evaluated in healthy volunteers using placebo patches. Placebo transdermal nitroglycerin patches (Transderm-Nitro 5 placebo, Ciba Pharmaceutical Company; Nitro-Dur 10 cm2 placebo, Key Pharmaceuticals; and Nitrodisc 5 placebo, Searle Laboratories) were supplied by the manufacturers. Eighty-two healthy subjects were randomly assigned to begin using one of the three brands of patches. Using a Latin-square crossover design, subjects applied each brand of patch daily for five days and crossed over to the other brands on study days 6 and 11. At the end of each study phase, subjects completed a written questionnaire designed to evaluate their overall acceptance of each brand of patch. A total of 80 subjects completed all three phases of the study. According to forced rank preference, 84% of subjects preferred the Ciba patch to one of the other two brands. Subjects judged the Ciba patch to be the easiest of the three brands to use and reported significantly fewer side effects and skin irritation while using the Ciba patch; they also preferred the size of the Ciba patch and experienced significantly fewer problems with adherence of the Ciba patch. A significant percentage of subjects indicated that they would prefer a transdermal patch over tablets or ointment. Most subjects preferred the Ciba patch over the Key patch or Searle patch.

Adhesiveness↗

Validated GC-MS analysis for the determination of residual fentanyl in applied Durogesic reservoir and Durogesic D-Trans matrix transdermal fentanyl patches.

The method development and validation characteristics are described of a simple gas chromatographic-mass spectrometric (GC-MS) analytical procedure to determine residual fentanyl in used Durogesic reservoir patches and Durogesic D-Trans matrix technology based systems to estimate the actual rate of transdermal fentanyl delivered in individual patients. The sample preparation protocol constituting a saline based extraction of sets of new patches of each nominal dose available, resulted in fentanyl extraction recoveries to increase steadily as a function of increasing extraction time. For the reservoir type transdermal therapeutic system (TTS), fentanyl extraction efficiencies at equilibrium (16 h) ranged from approximately 60% (100-microg/h TTS) to 95% (25-microg/h TTS), whereas for the matrix type system considerable lower recoveries were demonstrated for the highest nominal dose rates (35%-52%), while reaching 90% for the 25-microg/h system. For the latter type of fentanyl TTS, an optimized methanol based extraction protocol yielded virtually quantitative fentanyl recoveries for each matrix patch nominal dose level at substantially shorter extraction periods (15 min). The GC-MS analytical method using selected ion monitoring (SIM) and deuterated fentanyl as internal standard was shown to be adequately selective with regard to the presence of other compounds in the Durogesic patches. It was further demonstrated that the developed analytical protocols provided highly reproducible and accurate estimates of the initial fentanyl content of each patch type at all available nominal doses, with coefficients of variation and relative errors generally below 10%. These advantageous assay validation characteristics can be further transposed to the application of residual fentanyl level estimates in used patches, provided that with each batch of samples also a set of new TTSs with equal dose is assayed to perfectly mimic extraction phenomena. Finally, the presented GC-MS analytical protocol was successfully applied for the determination of residual fentanyl in a subset of 57 reservoir type patches obtained from four palliative patients.

Administration, Cutaneous↗

A fatal overdose of transdermally administered fentanyl.

We present a case of fentanyl overdose via mucous membrane absorption. A 31-year-old man presented to the emergency department in respiratory arrest. At intubation, a Duragesic transdermal patch (75 micrograms/h) was recovered from the buccal cavity. A second fentanyl transdermal patch (75 micrograms/h) was noted on the right lateral aspect of the thigh. Postmortem blood evaluation returned a venous fentanyl level of 17.2 micrograms/L. The therapeutic range for analgesic use is 1 microgram/L to 3 micrograms/L. Drug screens were positive for benzodiazepines and cocaine. Mass spectrophotometry/gas chromatography was used to determine fentanyl levels and to confirm drug screen results. Case history, findings at intubation, and high fentanyl blood concentration suggest the cause of respiratory arrest and death was fentanyl overdose.

Administration, Cutaneous↗

Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression.

BACKGROUND: A high frequency of cigarette smoking has been reported among individuals with major depression. In a previous study, transdermal nicotine produced short-term improvement in the mood of depressed patients. This study was undertaken to determine the effects of 4 days' administration of transdermal nicotine on mood in nonsmoking patients with major depression. METHOD: The effects of nicotine patches (17.5 mg) on 12 nonmedicated outpatients with major depression (DSM-III-R) were studied for 4 continuous days. Patients had to score 18 points or more on the Hamilton Rating Scale for Depression (HAM-D) (21 items) for admission into the study. The HAM-D (10 items), a visual analog scale, and a side effects scale were scored daily during the trial (baseline, 4 days of nicotine patches, and 4 days of follow-up). RESULTS: Two patients dropped out of the study owing to nausea and vomiting. Results of the visual analog scale and HAM-D (10 items) showed a significant (p < .01) improvement in depression after the second day of nicotine patches. Patients relapsed 3 or 4 days after the last nicotine dose. The side effects observed were an increase in saliva production, nausea, loss of appetite, and mild insomnia. CONCLUSION: Nicotine patches produced short-term improvement of depression with minor side effects. Because of nicotine's high risk to health, nicotine patches are not recommended for clinical use in depression. Analogue drugs may be developed in the future that may help improve depression without the risk of other major health problems.

Administration, Cutaneous↗

Nicotine replacement therapy for smoking cessation.

BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This reduces withdrawal symptoms associated with smoking cessation thus helping resist the urge to smoke cigarettes. OBJECTIVES: The aims of this review were:to determine the effectiveness of the different forms of NRT (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; to determine its effectiveness compared to other pharmacotherapies. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register in March 2004. SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or to no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow up of less than six months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of participants, the dose, duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was abstinence from smoking after at least six months of follow up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. For each study we calculated summary odds ratios. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed effect model. MAIN RESULTS: We identified 123 trials; 103 contributing to the primary comparison between NRT and a placebo or non-NRT control group. The odds ratio (OR) for abstinence with NRT compared to control was 1.77 (95% confidence intervals (CI): 1.66 to 1.88). The ORs for the different forms of NRT were 1.66 (95% CI: 1.52 to 1.81) for gum, 1.81 (95% CI: 1.63 to 2.02) for patches, 2.35 (95% CI: 1.63 to 3.38) for nasal spray, 2.14 (95% CI: 1.44 to 3.18) for inhaled nicotine and 2.05 (95% CI: 1.62 to 2.59) for nicotine sublingual tablet/lozenge. These odds were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2 mg gum (OR 2.20, 95% CI: 1.85 to 3.25). There was weak evidence that combinations of forms of NRT are more effective. Higher doses of nicotine patch may produce small increases in quit rates. Only one study directly compared NRT to another pharmacotherapy. In this study quit rates with bupropion were higher than with nicotine patch or placebo. REVIEWERS' CONCLUSIONS: All of the commercially available forms of NRT (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) are effective as part of a strategy to promote smoking cessation. They increase the odds of quitting approximately 1.5 to 2 fold regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the smoker. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT.

Administration, Cutaneous↗

Continuation of postmenopausal hormone replacement therapy in a large health maintenance organization: transdermal matrix patch versus oral estrogen therapy.

OBJECTIVE: To determine possible differences in continuation of postmenopausal estrogen replacement therapy among women initiating treatment with transdermal estradiol versus those initiating treatment with oral estrogen. STUDY DESIGN: A retrospective database search. PATIENTS AND METHODS: We analyzed estrogen use among 45- to 74-year-old women who filled index prescriptions for estrogen during 1996 for either once-a-week transdermal estradiol or daily oral estrogen. Prescription use was analyzed separately for each of 2 groups: 276 hysterectomized women who filled prescriptions for estrogen alone (ERT) and 4182 women who filled prescriptions for medroxyprogesterone acetate (MPA) with estrogen (HRT) on the same day. RESULTS: Risk of discontinuing therapy after 12 months ranged from 59% to 76% among the 4 subgroups: ERT with unopposed transdermal estradiol; ERT with unopposed oral estrogen; HRT with MPA-opposed transdermal estradiol; and HRT with MPA-opposed oral estrogen. The relative risk (RR) of discontinuation was significantly greater among women starting HRT with transdermal estradiol than among women starting oral estrogen (RR = 1.5; 95% confidence interval [CI] = 1.3 to 1.8). RR of discontinuation among women starting ERT with transdermal estradiol compared with women starting oral estrogen therapy was 1.3 (95% CI = 1.0 to 1.8). CONCLUSIONS: Approximately 2 of 3 women who start either ERT or HRT discontinue therapy within a year, regardless of hysterectomy status. Furthermore, women who start ERT or HRT with a transdermal estradiol system are more likely to discontinue therapy.

Administration, Cutaneous↗

Design of 9-beta-D-arabinofuranosyladenine (ara-A) transdermal delivery system for animal studies: regulation of drug concentration in vivo.

Transdermal delivery systems of 9-beta-D-arabinofuranosyladenine (ara-A), having controlling membranes of various permeabilities, were developed and applied to Azone-pretreated hairless mouse abdominal skin. It was confirmed that the blood concentrations of ara-A and its metabolite 9-beta-D-arabinofuranosylhypoxanthine (ara-H) in hairless mice are controlled by the permeability of the controlling membrane in the transdermal patch. Furthermore, these blood concentrations were found to closely agree with the values obtained from theoretical model calculations. Finally, but importantly, the "micropharmacokinetic" behavior of ara-A in cutaneous tissue could also be predicted. These results suggest that the transdermal patch may be employed in dermal and transdermal ara-A efficacy studies in the treatment of cutaneous herpes virus infections in hairless mice.

Administration, Cutaneous↗

Transdermal nicotine alters some of marihuana's effects in male and female volunteers.

Despite the fact that tobacco and marihuana are often used together, relatively little is known about the effects of this combination. In order to investigate the effects of the principal psychoactive component in tobacco smoke, nicotine, on marihuana-induced intoxication, we conducted a double blind, cross-over experiment using nicotine transdermal patches. Ten male and 10 female participants received either placebo or a 21 mg transdermal nicotine patch 4 h before smoking one of two marihuana cigarettes (1.99 or 3.51% delta-9-tetrahydrocannabinol (Delta(9) THC) content). Measurements of physiological activity (heart rate, blood pressure, and skin temperature) and subjective effects (self-reports of drug effects on visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI)) were made periodically before and for 3h after smoking. Nicotine pre-treatment enhanced several responses to marihuana, in particular, heart rate, reports of "stimulated" on the visual analog scales, and scores on the Amphetamine scale of the ARCI. Male participants reported a more pronounced effect of marihuana that persisted longer than that of the female participants. Compared to the male participants, female participants experienced an attenuated response to marihuana and were less affected by the drug combination. The results of this study show that nicotine can have an important influence on the subjective and physiological effects of smoked marihuana. These effects have implications for the safety and efficacy of marihuana smokers who are self-medicating with the nicotine transdermal patch to manage their tobacco dependence.

Administration, Cutaneous↗

Efficacy of a new transdermal nitroglycerin patch (Deponit 10) for stable angina pectoris.

In this double-blind randomized placebo-controlled crossover study, the antianginal and anti-ischemic effect of a new transdermal system, releasing 10 mg of nitroglycerin (NTG) over 24 hours, was assessed in 19 outpatients with stable exercise-induced angina pectoris. The trial consisted of a 3-day washout: a 1-week period with verum or placebo patch followed by a second 1-week period with the other patch. During the study only sublingual NTG was allowed, and its consumption and the number of attacks recorded. Treadmill exercise tests were performed at the end of washout before patch application (baseline test) and 3 and 24 hours, respectively, after each period of 7 days of application of 1 patch daily. Systolic blood pressure and heart rate did not vary significantly at rest in the 17 patients who completed the trial. Angina was reduced 31.3% and NTG consumption 34.3% (p less than 0.01) during the week with Deponit 10 as compared with placebo. Exercise duration increased 29 and 16.1% (p less than 0.001 and p less than 0.1, respectively) at 3 and 24 hours with a verum patch as compared with placebo. ST-segment depression at comparable loads decreased 69 and 40.5% (p less than 0.01) at 3 and 24 hours, respectively, after application of Deponit. Onset of angina was delayed and maximal heart rate-blood pressure product significantly increased at 3 and 24 hours of treatment. It is concluded that Deponit 10 patch is effective in reducing anginal attacks and in increasing exercise capacity up to 24 hours after application.

Administration, Cutaneous↗

Psychological and endocrine responses to psychosocial stress and dexamethasone/corticotropin-releasing hormone in healthy postmenopausal women and young controls: the impact of age and a two-week estradiol treatment.

In this placebo-controlled double-blind study, psychological and endocrine stress responses were investigated in healthy postmenopausal placebo-treated women (n = 15; 60-75 years; placebo via transdermal patches), healthy postmenopausal estradiol-treated women (n = 13; 60-79 years; 0.1 mg 17beta-estradiol daily via transdermal patches) and young controls (n = 15; 20-31 years; untreated). The aged subjects received estradiol or placebo treatment for 14 days. All subjects were then exposed to the 'Trier Social Stress Test' (TSST) and the dexamethasone (Dex)-human corticotropin-releasing hormone (hCRH) test (100 microgram hCRH after premedication with 1.5 mg Dex). Psychological parameters including perceived stressfulness, mood and subjective well-being were measured by visual analog scales, a mood questionnaire and a mood diary, respectively. Results show that the TSST induced significant increases in adrenocorticotropin (ACTH), free salivary cortisol, total plasma cortisol and heart rates (all p < 0.0001). Regardless of age, comparable hormonal response patterns were observed in the TSST as indicated by similar peak levels and recovery phases. Visual analog scales confirmed that the same amount of stress was experienced by young and elderly subjects. In both age groups, hCRH injection after Dex premedication provoked significant increases in ACTH, free salivary cortisol and total plasma cortisol (all p < 0.0001). In contrast to the psychosocial stressor, elderly women were found to respond with a markedly enhanced cortisol response compared to young controls in the Dex-CRH test (p < 0.025). Additional investigation of morning cortisol profiles could not reveal any age-related differences in basal hypothalamus-pituitary-adrenal (HPA) axis activity. Following estradiol treatment, estradiol levels significantly increased only in substituted postmenopausal women (p < 0.001) reaching concentrations typically found in younger women during the follicular phase of the menstrual cycle. Corticosteroid-binding globulin levels did not differ significantly between groups. When confronted with the TSST, no response differences emerged between the three groups. However, estradiol treatment appeared to blunt the total plasma cortisol response in the Dex-CRH test, resulting in smaller increases in untreated premenopausal women and estradiol-treated postmenopausal women compared to placebo-treated postmenopausal women (p < 0.02). In sum, no response differences were observed after confrontation with a psychosocial stress test in our sample of healthy elderly subjects. As shown with the Dex-CRH test, our data suggest that the negative feedback of the HPA axis in elderly women is altered. Moreover, the current data suggest that estradiol replacement may modulate HPA feedback sensitivity in humans.

Adrenocorticotropic Hormone↗

Effectiveness of transdermal fentanyl patch for treatment of acute pain due to oral mucositis in patients receiving stem cell transplantation.

The current study was performed to evaluate the effectiveness and safety of transdermal therapeutic system (TTS) fentanyl in the management of acute pain due to oral mucositis in patients receiving stem cell transplantation. A cohort of consecutive patients with painful oral mucositis were enrolled. Initially, 25 microg/h of TTS fentanyl was administered for the treatment of oral mucositis pain. The pain score, based on a visual analogue scale, and mood and quality of sleep as determined by EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Cancer 30), were all recorded before the treatment, then 2, 6, and 10 days later. Twenty-two patients with hematologic malignancies were enrolled. Three patients were excluded from the response assessment, as their TTS fentanyl treatment was stopped owing to related complaints, including severe dizziness, severe vomiting, and an extensive body rash. The total duration of the treatment was 8 days (range, 6-15 days) and the total amount of TTS fentanyl administered per patient was 2.21 at 25 microg/h and 0.63 at 50 microg/h. Six (31.6%) of the remaining 19 patients required an escalated dose of TTS fentanyl at 50 mug/h. The mean pain scores before treatment and 2, 6, and 10 days later were 6.68, 5.17, 3.42, and 2.13, respectively (P < .001). Eight (42.1%) and seven (36.8%) patients experienced improved sleep and mood after treatment, respectively. The TTS fentanyl was effective in both relieving oral mucositis pain with an excellent tolerability and improving the quality of life for hematological patients receiving high-dose chemotherapy with stem cell transplantation.

Adolescent↗

Influence of poly(ethylene glycol)-alpha-cyclodextrin complexes on stabilization and transdermal permeation of ascorbic acid.

The present study was conducted to investigate the effect of poly(ethylene glycol)-alpha-cyclodextrin (alpha-CD) complexes on stabilization and cutaneous permeation of ascorbic acid from specially prepared transdermal patches. Poly(ethylene glycol) citrate (6-armPEG) and its inclusion complex with alpha-CD were prepared and used for preparation of the transdermal patches. Duro-Tak 87-2979 was taken as an adhesive matrix in combination with ascorbic acid. A diffusion cell with an artificial membrane was used to evaluate the absorption of ascorbic acid from the patches. The influence of drug release of alpha-CD and two types of its PEG complexes (as the novel permeation enhancers) was tested. The 6-armPEG-alpha-CD complex consisting of a PEG-citric acid ester at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for ascorbic acid during UV assay. The release studies showed that the type of enhancer is important in diffusion of the drug across membrane. Furthermore, the diffusion of ascorbic acid was considerably enhanced in the presence of 6-armPEG-alpha-CD complex. Inclusion complexes of 6-armPEG with alpha-CD at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for UV method of assay. The present data suggest that 6-armPEG-alpha-CD complex is also useful in enhancing the release of ascorbic acid from the acrylic type pressure sensitive adhesives.

Administration, Cutaneous↗

Aerodiol versus the transdermal route: perspectives for patient preference.

OBJECTIVE: to compare the efficacy, tolerability and user preference of Aerodiol intranasal and transdermal patch administration of 17 beta-estradiol for climacteric symptoms. METHODS: an open-label, multicenter, crossover trial in which recently postmenopausal women were randomized to receive either Aerodiol 300 microg daily (n=176), or transdermal 17 beta-estradiol (reservoir patches delivering 50 microg/day), 2 patches per week (n=185), for 12 weeks, followed by 4 weeks of the alternative treatment. Efficacy was assessed primarily by the Kupperman index at the end of each treatment period. User satisfaction was assessed by questionnaire at weeks 12 and 16, and at week 16 the women chose which treatment they preferred to use for a further 40-week period. RESULTS: Aerodiol and transdermal patch therapy produced marked and similar reductions in the Kupperman index and the incidence of hot flushes at weeks 12 and 16. The reduction in the Kupperman index at week 12 was statistically equivalent for the two treatments. The tolerability of both treatments was good, with similar numbers of emergent adverse events reported in both groups. The incidence of moderate or severe mastalgia, however, was significantly lower with Aerodiol (P=0.02). Significantly more women chose to continue treatment with Aerodiol than with the transdermal patch (66 vs. 34%, P<0.001). When all women had experienced both treatments, reported levels of satisfaction were significantly higher with Aerodiol than with transdermal therapy (P<0.001 for all six categories assessed). CONCLUSIONS: Aerodiol and transdermal patch treatments were of similar efficacy and tolerability. Levels of user preference and satisfaction, however, were higher with Aerodiol, which should contribute towards good long-term compliance with this therapy.

Administration, Cutaneous↗