Skin penetration of topical formulations of ibuprofen 5%: an in vitro comparative study.

An in vitro isolated human skin technique with known reliable predictive value for in vivo performance was used to compare the skin penetration of the proprietary ibuprofen gel formulation, Ibugel, with five other commercially available topical formulations containing ibuprofen 5%: Ibuspray, Ibumousse, Proflex Cream, Fenbid Gel and Deep Relief Gel. There was a marked difference between some formulations in the percentage of applied ibuprofen penetrating the skin samples, with Ibuspray, Ibugel and Ibumousse showing the most efficient penetration. The percentage of applied ibuprofen penetrating the skin samples from these formulations was significantly greater (p < 0.05) at all sampling intervals when compared with Proflex Cream, Fenbid Gel or Deep Relief Gel. By 48 h, the percentage of applied ibuprofen that had penetrated through the skin samples from Ibuspray, Ibugel and Ibumousse was approximately 2.5 times greater than that from Deep Relief Gel, 3 times greater than that from Proflex Cream and 5 times greater than that from Fenbid Gel. The data demonstrate that, with topically applied preparations, the composition of the vehicle can have a significant impact on the percutaneous penetration of the active medicament. The possible reasons for this are discussed in terms of partition and diffusion phenomena. Different topical presentations of the same drug substance--especially agents like ibuprofen which are intended for subcutaneous action--cannot be assumed to be pharmaceutically and clinically equivalent or indeed interchangeable.

Comparative efficacy of a proprietary topical ibuprofen gel and oral ibuprofen in acute soft tissue injuries: a randomized, double-blind study.

The efficacy of a novel, proprietary topical formulation of ibuprofen 5% gel (Ibugel) and ibuprofen 400 mg tablets (1200 mg daily) was compared in a double-blind, double-dummy, parallel group study in patients with acute soft tissue injuries. Patients received either active gel plus placebo tablets (n = 50) or active tablets plus placebo gel (n = 50) for at least 7 days. The gel was applied and one tablet was taken three times daily. The two treatments showed similar efficacy. There were no significant differences between the groups for either the primary efficacy endpoint, the median time for the injury to be rated as 'completely better' by the patients (>14 days active gel, 13.5 days active tablets; P = 0.59), or for other efficacy measures including the times to clinically significant relief from pain at rest or on movement and swelling. In summary, ibuprofen gel shows similar efficacy to oral ibuprofen 400 mg and may offer improved tolerability.

An effective, cosmetically acceptable, novel hydro-gel emollient for the management of dry skin conditions.

BACKGROUND: A novel hydro-gel emollient (Doublebase) has been developed with improved moisturizing effects. OBJECTIVE: To test this novel hydro-gel for its moisturizing effect, for its potential to cause skin irritancy/allergy and for its clinical effectiveness and acceptability in dry skin conditions. METHODS/RESULTS: Skin hydration (corneometry) and trans-epidermal water loss (TEWL) studies with a single application in 18 volunteers confirmed its efficacy (p < 0.0001) and showed that it was superior to Ultrabase and Diprobase (p < 0.001). Skin hydration studies with multiple applications in 12 volunteers also showed that it was superior to Ultrabase and Diprobase (p < 0.0001). Irritation tests in 74 eczema-prone patients resulted in only one mild reaction, and allergy tests in 99 healthy volunteers elicited no positive reactions. The clinical acceptability and effectiveness of Doublebase was demonstrated in an open study of 78 patients with dry skin conditions. CONCLUSION: Doublebase may be considered a suitable preparation that can be used effectively by most patients with dry skin conditions.

Efficacy of a proprietary ibuprofen gel in soft tissue injuries: a randomised, double-blind, placebo-controlled study.

The efficacy of a novel, proprietary topical formulation of ibuprofen 5% gel (Ibugel) was evaluated in a placebo-controlled study in patients with soft tissue injuries. Patients received either active gel (n=40) or placebo gel (n=41) for a maximum of seven days. Pain and interference with physical activity were assessed daily using visual analogue scales. There was a significant difference (p<0.001) in favour of active treatment for the time to achieve clinically meaningful reduction in pain. By day 7, 75% of patients in the active gel group had a clinically meaningful reduction of pain compared with 39% of patients who received placebo. Despite differences between study centres, the data for interference with physical activity also showed an advantage for active treatment. By day 7, 79% of patients in the active gel group had a clinically meaningful reduction in interference with physical activity, compared with 44% of patients who received placebo.

Analysis of the cyclin-dependent kinase inhibitors p18 and p19 in mantle-cell lymphoma and chronic lymphocytic leukemia.

BACKGROUND: Mantle-cell lymphoma (MCL) is characterized by overexpression of the G1 cyclin, cyclin D1, strongly implicating this cell-cycle regulatory element in MCL pathogenesis. Recently, loss-of-function mutations in cell-cycle negative regulatory elements, including p53 point mutations and deletions of the cyclin-dependent kinase inhibitors (CDKI) p15 and p16 have been described in a subset of MCLs and have been associated with aggressive clinical course, blastic morphology, and extranodal dissemination. The objective of the present study was to analyze two newly identified members of the p16 (INK4A; MTS1) CDKI family, p18 and p19, in MCL. Such analyses have not been previously reported. PATIENTS AND METHODS: DNA was isolated from tissue biopsies, peripheral blood cells, or bone marrow cells of 45 patients with MCL and 15 with chronic lymphocytic leukemia (CLL). Southern blot analysis was performed with p18 and p19 probes and compared to placental control DNA and to control probe hybridizations for evidence of p18 or p19 gene deletion or rearrangement. RESULTS: P18 deletion was identified in one MCL but in no case of CLL. One MCL sample had rearrangement of the p18 gene; this case also had coexisting homozygous p15 and p16 deletion. Both cases with p18 abnormalities had blastic morphology, and one had extranodal disease with renal parenchymal invasion. CONCLUSIONS: P18 rearrangement or deletion as detected by Southern blot is a rare event in MCL, but may be associated with blastic morphology. P53 mutations and deletions of the CDKI p15 and p16 appear to be more frequent in MCL, although further studies are necessary to assess the presence of inactivating point mutations or altered expression of p16 family proteins.

Evaluation of a therapeutic concentration of dithranol in the mouse-tail test.

A study of dithranol ointment in the mouse-tail test showed that 0.2% dithranol ointment induced a granular layer and orthokeratosis in mouse-tail epidermis. This provides further evidence of the value of the mouse-tail test in evaluating anti-psoriatic activity of topical preparations.

Short-contact anthralin therapy for psoriasis using an aqueous cream formulation.

A pilot study of five patients was conducted using an aqueous anthralin cream (Drithocreme) and demonstrated that between twenty and forty minutes was an effective contact time to produce an improvement in induration of psoriatic plaques. In a further, bilateral controlled study, the anthralin cream was used to treat twenty patients with symmetrical chronic plaque psoriasis. The cream was applied to one side of the body overnight and then to the other side in the morning. Thirty minutes later it was washed off both sides in a bath or shower. The results indicated that both overnight and short-contact treatment were equally effective, and the short-contact treatment reduced staining and irritation.

Hexyl-nicotinate-induced vasodilation in normal human skin.

Hexyl nicotinate in a lotion formulation was applied topically to the skin of 10 healthy volunteers with clinically normal skin. Erythematous responses were assessed visually and skin blood flow determined by means of a laser Doppler flow meter which measures the blood cell flux (Pf2 Perimed, Sweden). Mean erythematous responses and increased blood cell flux were dose-related but in several subjects increases in blood flow occurred in the presence of barely detectable erythematous responses. In some subjects, hexyl nicotinate may be an effective cutaneous vasodilator even in the presence of minimal erythema.

Anthralin: historical and current perspectives.

Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.