Nanostructured lipid carriers as semisolid topical delivery formulations for diflucortolone valerate.

CONTEXT: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption. OBJECTIVE: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption. METHOD: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol™ or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs. RESULTS AND DISCUSSION: DFV-loaded NLC formulations possessed average particle size ranging from 160.40 nm to 743.7 nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12 h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation. CONCLUSION: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.

Inflammatory tinea pedis with bacterial superinfection effectively treated with isoconazole nitrate and diflucortolone valerate combination therapy.

Undetected tinea pedis in a patient with diabetes can lead to serious bacterial infections with potentially serious consequences, such as foot amputations. Here we report on a 60-year-old patient with diabetes presenting with pain, severe pruritus, and malodour in the foot's interdigital area, and subsequently, diagnosed with inflammatory tinea pedis with bacterial superinfection. The patient was successfully treated with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%; marked improvement occurred within 5 days.

Misdiagnosed zoophile tinea faciei and tinea corporis effectively treated with isoconazole nitrate and diflucortolone valerate combination therapy.

There have been few published reports on the human transmission of Trichophyton mentagrophytes, a zoophilic fungus frequently occurring in pets. Here we report on 2 girls, living with a pet dwarf rabbit, who presented with inflammatory skin lesions positive for T. mentagrophytes and subsequently diagnosed as zoophile tinea faciei and tinea corporis. The patients were successfully treated with systemic terbinafine and 2-week therapy with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%.

Trichophyton mentagrophytes cause underestimated contagious zoophilic fungal infection.

Trichophytia infection, paraphrased cuddly toy mycosis, occurs primarily in prepubertal children, occasionally in infants and adults. The presented case shows the highly contagious infection of four family members with Trichophyton mentagrophytes. Effective treatment requires detailed diagnostic: identifying the dermatophyte, finding the infection source, treating the infection carriers. Tinea must be treated systemically and topically because of infectivity and ignitability. Systemic terbinafine or fluconazole treatment and topical fixed combination isoconazole nitrate/diflucortolone valerate are recommended.

Effective treatment of erythrasma-associated inflammation and pruritus with isoconazole nitrate and diflucortolone valerate combination therapy.

A warm and moist environment is a common risk factor for erythrasma, a condition characterized by pruritic, scaly and erythematous tan patches on the skin. Here we report on a 13-year-old athletic student presenting with pruritus and mild burning on her left medial thigh, and subsequently diagnosed with erythrasma. The patient was successfully treated with a 5-day regimen of Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%.

Rapid relief of intertrigo-associated pruritus due to Candida albicans with isoconazole nitrate and diflucortolone valerate combination therapy.

A 43-year-old male, with intertrigo due to Candida albicans located at the inguinal folds and accompanied by severe pruritus, was treated with topical 1% isoconazole nitrate and 0.1% diflucortolone valerate (2 applications/day for 7 days). An improvement of pruritus was reported 2 days after the beginning of the treatment. Skin lesions improved after 3 days of treatment. Complete remission of both skin lesions and pruritus was observed at day 7. No side effects were observed.

Effective treatment of tinea corporis due to Trichophyton mentagrophytes with combined isoconazole nitrate and diflucortolone valerate therapy.

Trichophyton mentagrophytes is the dermatophyte species most commonly reported in cases of guinea pig-associated dermatophytosis (or guinea pig fungus) a condition that more often affects children than adults. In this case, a 13-year-old girl with recent direct contact with guinea pigs presented with a previously undertreated inflammatory skin lesion on the left side of her upper body, which was positive both for Trichophyton mentagrophytes and Staphylococcus epidermidis. The condition was subsequently diagnosed as tinea corporis due to Trichophyton mentagrophytes with concomitant bacterial infection and effectively treated with 2 weeks of twice-daily application of Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%. Visible improvement in the lesion was apparent after only 1 week of treatment.

Isoconazole nitrate: a unique broad-spectrum antimicrobial azole effective in the treatment of dermatomycoses, both as monotherapy and in combination with corticosteroids.

Fungal skin infections, or dermatomycoses, are associated with a broad range of pathogens. Involvement of gram-positive bacteria is often suspected in dermatomycoses. Inflammation plays an important role in dermatomycoses, displaying a close association between frequent inflammation and reduced skin-related quality of life. Isoconazole nitrate (ISN) is a broad-spectrum antimicrobial agent with a highly effective antimycotic and gram-positive antibacterial activity, a rapid rate of absorption and low systemic exposure potential. ISN is effective against pathogens involved in dermatomycoses, with minimum inhibitory concentrations well below the concentration of ISN in skin and hair follicles. The combination of the corticosteroid diflucortolone valerate with ISN (Travocort) increases the local bioavailability of ISN. Compared with ISN monotherapy, Travocort has a faster onset of antimycotic action, faster relief of itch and other inflammatory symptoms, improved overall therapeutic benefits and earlier mycological cure rate. Travocort is effective in the treatment of inflammatory mycotic infections, and also in the eradication of accompanied gram-positive bacterial infections. The rapid improvement observed with Travocort treatment, combined with favourable safety and tolerability, results in higher patient satisfaction, and therefore, can be an effective tool to increase treatment adherence in patients with dermatomycoses accompanied by inflammatory signs and symptoms.

Isoconazole nitrate vs isoconazole nitrate and diflucortolone valerate in the treatment of tinea inguinalis: results of a multicenter retrospective study.

BACKGROUND AND OBJECTIVE: Many tinea inguinalis infections are characterized by pronounced inflammatory lesions and pruritus. Therefore, a therapy with a topical corticosteroid in addition to a topical antimycotic agent might be beneficial. In this multicenter, retrospective study, we compared the mycological and clinical efficacy and tolerability of isoconazole nitrate alone vs isoconazole nitrate and diflucortolone valerate in 58 adult patients with tinea inguinalis. PATIENTS AND METHODS: Treatment duration was three weeks. The efficacy of the treatment was based on the assessment of several signs and symptoms, which were collected on a 4-point scale. All patients were examined clinically before the beginning of the treatment, one week later, two weeks later, and at the end of the treatment. Mycological examinations were performed before the beginning of the treatment and at the end of the study. RESULTS: Treatment results with the combination of isoconazole nitrate and diflucortolone valerate were superior regarding erythema and pruritus. Both erythema and pruritus resolved in a larger percentage of patients and more quickly. Both regimens were well tolerated. Mycological cure rates were similar in both groups of patients. CONCLUSIONS: Combination therapy with isoconazole nitrate and diflucortolone valerate is an effective and well-tolerated regimen in adult patients with tinea inguinalis.

Liquid chromatographic and spectrophotometric determination of diflucortolone valerate and isoconazole nitrate in creams.

A new RP-LC method and two new spectrophotometric methods, principal component regression (PCR) and first derivative spectrophotometry, are proposed for simultaneous determination of diflucortolone valerate (DIF) and isoconazole nitrate (ISO) in cream formulations. An isocratic system consisting of an ACE C18 column and a mobile phase composed of methanol-water (95 + 5, v/v) was used for the optimal chromatographic separation. In PCR, the concentration data matrix was prepared by using synthetic mixtures containing these drugs in methanol-water (3 + 1, v/v). The absorbance data matrix corresponding to the concentration data matrix was obtained by measuring the absorbances at 29 wavelengths in the range of 242-298 nm for DIF and ISO in the zero-order spectra of their combinations. In first derivative spectrophotometry, dA/dlambda values were measured at 247.8 nm for DIF and at 240.2 nm for ISO in first derivative spectra of the solution of DIF and ISO in methanol-water (3 + 1, v/v). The linear ranges were 4.00-48.0 microg/mL for DIF and 50.0-400 microg/mL for ISO in the LC method, and 2.40-40.0 microg/mL for DIF and 60.0-260 microg/mL for ISO in the PCR and first derivative spectrophotometric methods. These methods were validated by analyzing synthetic mixtures. These three methods were successfully applied to two pharmaceutical cream preparations.

Therapeutic use of topical corticosteroids in the vesiculobullous lesions of incontinentia pigmenti.

Incontinentia pigmenti (IP) is a rare genodermatosis caused by a mutation of nuclear factor kappa B essential modulator gene. There is no specific treatment for IP, therefore it has been claimed that there is no effective treatment to hasten resolution of any of the phases of IP. However, the initial vesiculobullous stage of IP is characterized histopathologically by eosinophilic inflammation, which is expected to respond to corticosteroids. An 18-day-old female neonate was seen, with vesicles on her trunk and limbs diagnosed as the vesiculobullous stage of IP. The patient was treated with a double-compound cream containing a potent corticosteroid (difluocortolone valerate 0.1%) and an antiseptic (chlorquinaldol 1%), to be applied to the lesions twice daily. Five days later, resolution of the lesions was almost complete. As chlorquinaldol has no known anti-inflammatory activity, we attribute this improvement to difluocortolone valerate. This case shows that early lesions of IP with eosinophilic inflammation are treatable.

The advantages of topical combination therapy in the treatment of inflammatory dermatomycoses.

Dermatomycoses are contagious superficial fungal infections, which are highly prevalent in developed and developing countries. Caused by a range of Epidermophyton, Microsporum and Trichophyton species, dermatomycoses manifest on glabrous skin as 'ringworm', an annular scaly lesion with a variable inflammatory component. Itch is the chief subjective symptom, particularly in tinea cruris. Unless lesions are extensive or resistant to local therapy, dermatomycoses of glabrous skin are treated with topical antifungal agents, such as imidazoles and allylamines. Studies show, however, that the addition of a topical corticosteroid to imidazole therapy increases the bioavailability and prolongs the activity of the antimycotic, while rapidly reducing inflammatory symptoms. Travocort is a combination of 1% isoconazole nitrate (ISN), a broad-spectrum imidazole with established antimicrobial activity and antimycotic efficacy, and 0.1% diflucortolone valerate (DFV), a potent topical corticosteroid with low systemic absorption and therefore a low risk of systemic glucocorticoid side-effects. In randomised, double-blind controlled clinical trials, Travocort therapy showed a more rapid onset of action, faster relief of itch and other inflammatory symptoms, improved overall therapeutic benefits and better mycological cure rate during the first 2 weeks of treatment compared with ISN monotherapy. Travocort is well tolerated and, because of prolonged ISN retention in the skin, provides antifungal protection against reinfection for some weeks after therapy.

Cushing's syndrome and adrenocortical insufficiency caused by topical steroids: misuse or abuse?

BACKGROUND: Prolonged application of topical steroids transiently suppresses the hypothalamic-pituitary-adrenal axis (HPA). Infants who are exposed to topical corticosteroids have greater risk for Cushing's syndrome or adrenocortical insufficiency caused by suppression of the HPA axis because glucocorticoids are highly absorbed through the diaper area. Here, we report six infants (four girls, two boys) aged between 3 and 8 months who were exposed to potent topical corticosteroids (clobetasol propionate and diflucortolone valerate) by the mother's application without prescription. METHODS: We examined the HPA axis and other side effects of the potent glucocorticoid therapy in these infants. After stopping the topical corticosteroid, serum AST, ALT, lipids, morning cortisol and ACTH levels were measured. A low dose ACTH stimulation test was carried out. Hydrocortisone was started for the prevention of glucocorticoid withdrawal syndrome and the dose was gradually decreased. Abdominal ultrasonography was performed to investigate hepatosteatosis. RESULTS: The ACTH stimulation test showed suppression of the HPA axis in these infants. Hepatomegaly was found in all infants and three of them had hepatosteatosis. Liver transaminase levels were elevated in five infants. Five patients have been followed for 6-14 months. One infant died due to generalized Cytomegalovirus infection. CONCLUSION: We emphasize that physicians should be alert for the dangerous side-effects of topical steroids and they should avoid long-term use. Furthermore, parents should be informed about the side-effects when topical steroid treatment is chosen.

Paederus dermatitis in Sierra Leone.

Paederus dermatitis, a type of irritant contact dermatitis attributed to a Staphylinid beetle, is prevalent in most parts of the world. We studied 50 cases of Paederus dermatitis at the United Nations Hospital at Koidu Sierra Leone (West Africa), over a period of 6 months from Oct 2003 to Mar 2004. The objectives of the study were to determine clinical patterns of dermatitis and its response to topical steroids, with and without antibiotics. Patients with a definite history of contact with the insect were included in the study. Amongst these, 14 of the more severe cases were treated with oral prednisolone or intralesional triamcinolone acetonide. The remainder of the 36 patients were divided in two equal groups A and B. Patients in Group A were treated with topical diflucortolone valerate 0.001 percent and oral cetirizine hydrochloride; patients in group B were given oral ciprofloxacin in addition. In 50 patients studied, 43 (86%) were males and 7 (14%) were females. The neck was the most common site involved followed by face. Healing time ranged from 14 to 28 days and lesions in all the patients healed with residual dyschromia. Healing time was shorter in Group B patients in comparison with those in Group A. Paederus dermatitis in Sierra Leone is a relatively severe form of this dermatitis. The better response to a combination of topical steroids and oral antibiotics may indicate concurrent bacterial infection.

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations.

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.

Effect of a topical steroid on gene expressions for chemokines in mice with contact hypersensitivity.

Effects of a topical corticosteroid drug, diflucortolone valerate, on the mRNA expressions for four CC- and four CXC-chemokines, which have been reported to be associated with recruitment of different kinds of proinflammatory and inflammatory cells, were investigated by RT-PCR in mice with 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) response. All of the eight gene expressions were clearly up-regulated in the lesion site of the CHS response up to 24 h post-challenge of TNCB at which ear swelling response reached a peak, so that heavy infiltration of inflammatory cells consisting mainly of mononuclear cells and neutrophils was likely induced by these chemokines. Topical treatment with diflucortolone valerate suppressed completely the infiltrates as well as the ear swelling response. In addition, the up-regulation of gene expressions for these eight chemokines were suppressed by the treatment, indicating that the corticosteroid drug attenuates the expression of chemokine genes essential for orientating nonspecific skin response to hapten-specific CHS response through the recruitment of inflammatory cells from the circulation into the tissue site.

Comparative toxicity study of hydrocortisone 17-butyrate 21-propionate (HBP) ointment and other topical corticosteroids in rats.

Comparative systemic and topical toxicity in male rats treated on the dorsal skin for 14 consecutive days with a volume of 0.15 g/100 g (body weight) of 0.1% hydrocortisone 17-butyrate 21-propionate (HBP) ointment, 0.05% clobetasol propionate (CP) ointment, 0.1% predonisolone 17-valerate 21-acetate (PVA) ointment and 0.1% diflucortolone valerate (DV) ointment was studied. In all the treated groups body weight gain was suppressed, serum concentration of total cholesterol and triglycerides increased and the lymphatic tissues and skin were atrophic. The DV and CP groups had adrenal atrophy and renal lesions, and the DV group also had gastric and hepatic lesions. The systemic effect of HBP ointment was weaker than that of the other drugs (DV greater than CP much greater than PVA greater than HBP). All the drugs significantly reduced the skin fold thickness in treated areas throughout the application period. The dermal atrophic effect of HBP ointment was also relatively weaker than that of the other drugs. From the above evidence, it was concluded that HBP ointment was less toxic than the other topical corticosteroids.

Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.

A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.