Comparative study of novel green UV-spectrophotometric platforms for simultaneous rapid analysis of flumethasone pivalate and clioquinol in their combined formulation.

Flumethasone pivalate (FP) and clioquinol (CL) formulation was developed as a prodigious remedy to cure the external ear inflammatory disorders. So, the current research introduces five smart and novel UV-spectrophotometric platforms relying on minimal mathematical manipulation steps for simultaneous green analysis of FP and CL with no preliminary separation in their formulation that suffered from the high difference of their ratio and severe spectral overlapping. These platforms involved dual-wavelength, first derivative ratio, Fourier self-deconvolution, area under the curve, and bivariate methods. The suggested platform' linearity was observed over the concentration range of 3-42 µg/ml for FP and 1.5-8 µg/ml for CL. All suggested platforms were validated according to ICH recommendations regarding accuracy, precision, repeatability, and selectivity producing satisfactory results within the accepted limits. These platforms were represented as rapid, green, and cheap alternatives to the reported chromatographic method due to lower solvent consumption and waste generation. Furthermore, they improved the determination sensitivity of the studied drugs and enhanced the recorded data signals or its spectral resolution by the newly introduced Fourier self-deconvoluted method. The statistical comparison between the results of the suggested platforms with each other and with those of the reported method showed no significant differences between them.

A comparison of Locacorten-Vioform and clotrimazole in otomycosis: A systematic review and one-way meta-analysis.

OBJECTIVES/HYPOTHESIS: The goal of this systematic review was to compare the efficacy and ototoxicity of Locacorten-Vioform (Paladin Labs Inc., Montreal, Quebec, Canada) and clotrimazole in the treatment of patients with otomycosis. DATA SOURCES: Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, World Health Organization International Clinical Trials Registry Platform, European Union Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov. METHODS: We included any randomized controlled trials or nonrandomized studies (case-control, cohort, and case series) assessing the topical use of Locacorten-Vioform (Paladin Labs Inc.) and/or clotrimazole in adult and/or pediatric immunocompetent patient population with otomycosis. DerSimonian and Laird's random effects approach was used for meta-analysis, followed by an assessment of heterogeneity and subgroup analysis. RESULTS: Of 226 reviewed articles, 14 were retained. Clotrimazole efficacy rate was 85% (95% confidence interval [CI]: 79.7-89.0%), whereas Locacorten-Vioform (Paladin Labs Inc.) was 73% (95% CI: 56.0-84.5%). Overall, study quality was low. There was high heterogeneity in both groups (I(2) of 47 and 49). There were only three studies assessing Locacorten-Vioform (Paladin Labs Inc.); therefore, comparative assessment was not possible. A one-way meta-analysis involving 13 clotrimazole studies was performed. Heterogeneity across studies was high; however, studies using objective analysis assessing treatment efficacy, randomized controlled trials, studies using drops, studies performed in Asia, and studies where Candida was the major fungus at diagnosis demonstrated low heterogeneity. CONCLUSION: Although both are safe and effective, there is insufficient evidence supporting increased efficacy of either clotrimazole or Locacorten-Vioform (Paladin Labs Inc.) for the treatment of otomycosis. High-quality comparative studies are required. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:1411-1419, 2016.

Novel spectrophotometric determination of flumethasone pivalate and clioquinol in their binary mixture and pharmaceutical formulation.

This work is concerned with development and validation of three simple, specific, accurate and precise spectrophotometric methods for determination of flumethasone pivalate (FP) and clioquinol (CL) in their binary mixture and ear drops. Method A is a ratio subtraction spectrophotometric one (RSM). Method B is a ratio difference spectrophotometric one (RDSM), while method C is a mean center spectrophotometric one (MCR). The calibration curves are linear over the concentration range of 3-45 µg/mL for FP, and 2-25 µg/mL for CL. The specificity of the developed methods was assessed by analyzing different laboratory prepared mixtures of the FP and CL. The three methods were validated as per ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits.

Tympanoplasty graft preparation using ear drops containing polyethylene glycol, flumethasone and clioquinol.

The aim of tympanoplasty graft preparation is to stiffen the fascia or perichondrium and thereby to optimise ease of manipulation. We report 39 cases utilising a novel technique in which the graft is prepared in ear drops containing polyethylene glycol, flumetasone pivalate (0.02 per cent) and clioquinol (1 per cent). This technique is useful in reducing the risk of desiccation if placement is delayed, and may pose less risk of infection and mechanical damage than alternative methods.

Lecithin based nanoemulsions: A comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation.

Charged drug delivery systems are interesting candidates for the delivery of drugs through skin. In the present study, it was possible to create negatively and positively charged oil/water nanoemulsions by using sucrose laureate and polysorbate 80 as non-ionic surfactants. The positively charged nanoemulsions were generated by adding cationic phytosphingosine (PS). The relationship between the physicochemical properties of the nanoemulsions was shown by particle size and zeta potential measurements. These properties were dependent on the type of non-ionic surfactant and the concentration of PS. Furthermore the cationic PS had a positive impact on the skin permeation rates (flux) of the incorporated model drugs fludrocortisone acetate and flumethasone pivalate. An enhancement factor between 1.1 and 1.5 was obtained in relation to the control. The interaction of pre-impregnated porcine skin with positively and negatively charged nanoemulsions was confirmed by DSC analysis. The generated DSC-curves showed a slight difference in the phase transition temperature assigned to the characteristic lipid transition. However, it was not possible to assign the effect to one of the ingredients in the multicomponent system.

Effect of selected fluorinated drugs in a "ringing" gel on rheological behaviour and skin permeation.

The purpose of the present study was to investigate the influence of different drugs exhibiting different solubility on the viscoelastic properties and on the skin diffusion profile of a ringing gel. In a preliminary rheology study with the placebo gel predominating elastic properties were confirmed and a temperature influence was indicated. Fluconazole, fludrocortisone-acetate, flumethasone-pivalate, flutamide and flufenamic-acid each 1% (w/w) were incorporated into the preparation and oscillatory measurements were performed at temperatures of 25, 28, 32 and 37 degrees C. In all drug containing formulations a high elastic G' value predominated the viscous G'' value. The highest G' value could be obtained with the incorporated flumethasone-pivalate. Additionally in almost all cases the G' values decreased with increasing temperature compared to the placebo gel. Additionally in vitro standard diffusion experiments using Franz-type cells and porcine skin were performed. Following rank order of the cumulative drug release after 48 h was obtained: fluconazole>flufenamic-acid>flumethasone-pivalate>flutamide>fludrocortisone-acetate. Furthermore an excellent chemical stability of all incorporated drugs was confirmed over 10 weeks.

Medical treatment of vulvar squamous cell hyperplasia.

OBJECTIVE: To evaluate symptomatic response and recurrence rates of graduated topical fluorinated corticosteroid in patients with vulvar squamous cell hyperplasia. METHODS: Nine hundred seventy-six patients with biopsy-proven vulvar squamous cell hyperplasia from 1990 to 2003 were reviewed in this retrospective study. All patients were treated with graduated topical fluorinated corticosteroid. Data were obtained from hospital records. Symptomatic remission and recurrence rates were noted following six months local therapy. RESULTS: The mean age was 42.55+/-10.93 (15-85). The remission rate was 93.8% in six months. The remission rate was non-significantly higher in postmenopausal patients than that in their premenopausal counterpart (94.9% vs 93.0%, p=0.15). The disease recurred in 6.9% of patients. Of the patients that suffered recurrence 47.5% had persistent disease initially. The patients with following factors older ages (>40 years), postmenopausal period had significantly higher recurrence rates. Four patients with recurrent disease and six patients with persistent disease in the form of vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia, were treated with skinning vulvectomy. CONCLUSION: Corticosteroid in the treatment of vulvar squamous cell hyperplasia yielded excellent response rates. In the evaluation of patients without symptomatic relief, the first step should be a vulvar biopsy to exclude the presence of atypical components.

Otic drops used to clear a blocked grommet: an in vitro prospective randomized controlled study with blinded assessment.

Clinicians often prescribe otic drops anecdotally to try and clear grommets blocked with blood. We carried out an in vitro double-blind randomized controlled study comparing the efficacy of sodium bicarbonate, Locorten Vioform and olive oil drops in clearing Shah grommets placed in 'artificial ears' and blocked with blood in a standardized fashion. There were 33 grommets in each group, and drops were inserted three times a day for 7 days. Olive oil drops cleared 17 of 33 (51.51%), Locorten Vioform cleared one of 33 (3%) and sodium bicarbonate cleared zero of 33 (0%) blocked grommets. Statistical comparison between pairs indicates that olive oil was significantly better than both Locorten Vioform (P < 0.001) and sodium bicarbonate drops (P < 0.001) at clearing grommets blocked with blood.

Patient compliance with short-term topical aural antibiotic therapy.

Little is known about patient compliance with topical aural antibiotic regimens. The compliance of 50 patients with unilateral otitis externa attending an otolaryngology clinic was studied by comparing the weight of dispensed topical ear preparations before and after completion of a 7-day-course of treatment. A standard was obtained from controlled administration of the preparation under laboratory conditions and the performance of different delivery systems evaluated. Thirty-seven patients re-attended for review with their medication. A total of 34 of 50 patients entering the study (70%) satisfied conventional criteria for compliance. However, over-use of preparations was common and stricter criteria are proposed and applied. Compliance was significantly increased when someone other than the patient administered the preparation.

Combination dermatological products: a comparison of betamethasone dipropionate/clotrimazole/gentamicin sulphate and flumethasone pivalate/clioquinol creams.

The combination creams, betamethasone dipropionate/clotrimazole/gentamicin sulphate and flumethasone pivalate/clioquinol, were compared in patients with corticosteroid responsive dermatoses and/or cutaneous fungal and/or bacterial infections. Medication was applied to affected areas twice daily for 28 days. Of 67 patients enrolled, 31 treated with betamethasone/clotrimazole/gentamicin and 33 given flumethasone pivalate/clioquinol were evaluated for efficacy and safety each week during therapy and once 14 days post-therapy. Disease signs and symptoms were less severe in the group given betamethasone/clotrimazole/gentamicin than in the comparative group at days 7 (P = 0.04), 21 (P = 0.02), 28 (P = 0.09), and 42 (P = 0.09) and at patients' last valid visit (P = 0.06). By the last valid visit, signs/symptoms had improved by 82% for patients treated with betamethasone/clotrimazole/gentamicin versus 68% for those treated with flumethasone pivalate/clioquinol. Patients given betamethasone/clotrimazole/gentamicin had statistically significantly better therapeutic responses than those given flumethasone pivalate/clioquinol at day 7 and, by the last valid visit, 19/31 (61%) patients given betamethasone/clotrimazole/gentamicin compared to 15/33 (45%) given flumethasone pivalate/clioquinol had a complete cure or an excellent therapeutic response. Median time of onset of relief of erythema and pruritus was approximately 2 days, regardless of treatment. No adverse reactions were reported.

Adrenocortical suppression by topical application of glucocorticosteroids in infants with seborrheic dermatitis.

Fifteen infants with seborrheic dermatitis were treated with topical glucocorticosteroids (flumethasone pivalate 0.02%). Early morning plasma cortisol levels were determined prior to treatment, during the 10-day treatment period, and 2 days after its termination. The mean plasma cortisol level prior to treatment was 8.8 +/- 3.4 micrograms%; after 2 days of application there was a significant decrease of the mean to 2.5 +/- 1.3 micrograms% that persisted throughout the treatment period. Two days after termination of treatment, the mean plasma cortisol level rose to 7.1 +/- 3.7 micrograms% but in five infants was still less than 5 micrograms% and in two less than 2 micrograms%, the latter two having shown the greatest involvement of the skin. The possibility of pituitary/adrenocortical inhibition similar to that observed with the systemic administration of glucocorticosteroids and the potential associated risks should be considered when treating cases that would require extensive application of flumethasone pivalate in infants.

Flumethasone pivalate (Locorten) in the treatment of oral diseases.

The combination flumethasone pivalate + iodochlorohydroxychinoline drops was used in 40 patients, 24 males and 16 females, mean age 42.6 years, suffering from infectious enanthema (35%), periodontitis (30%), aphthous stomatitis (25%) and abscess due to prosthesis (10%). After application of 2-3 drops of the combination t.i.d. for 2-7 days, satisfactory results were obtained in all the patients. Tolerance was good; mild unwanted effects occurred in 2 patients (5.0%). Thus the combination flumethasone pivalate + iodochlorohydroxychinoline appears to be very effective in the treatment of oral diseases because its action is more rapid and stronger than that of other currently used drugs.