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This paper proposes a novel approach to build integer multiplication circuits based on speculation, a technique which performs a faster -but occasionally wrong- operation resorting to a multi-cycle error correction circuit only in the rare case of error. The proposed speculative multiplier uses a novel speculative carry-save reduction tree using three steps: partial products recoding, partial products partitioning, speculative compression. The speculative tree uses speculative (m:2) counters, with m>3, that are faster than a conventional tree using full-adders and half-adders. A technique to automatically choose the suitable speculative counters, taking into accounts both error probability and delay, is also presented in the paper. The speculative tree is completed with a fast speculative carry-propagate adder and an error correction circuit. We have synthesized speculative multipliers for several operand lengths using the UMC 65nm library. Comparisons with conventional multipliers show that speculation is effective when high-speed is required. Speculative multipliers allow reaching a higher speed compared with conventional counterparts and are also quite effective in terms of power dissipation, when a high speed operation is required

In an effort to increase the efficacy of topical medications for treating onychomycosis, several new nail penetration enhancers were recently developed. In this study, the ability of 10% (wt/wt) miconazole nitrate combined with a penetration enhancer formulation to permeate the nail is demonstrated by the use of a selection of in vitro nail penetration assays. These assays included the bovine hoof, TurChub zone of inhibition, and infected-nail models.KEYWORDS miconazole, onychomycosis, topical T opical medications to treat tinea unguium have lacked efficacy (1, 2), and there has been a recent drive to improve ungual drug delivery by the development of nail-specific penetration enhancers (3-5). In this study, the ability of 10% (wt/wt) miconazole nitrate combined with a penetration enhancer formulation to permeate the nail was demonstrated by the use of a selection of in vitro nail penetration assays.Three different assays were used to test permeation by enhanced miconazole nitrate solution, as described below.Bovine hoof model. Sterile hoof discs measuring 0.5 to 1.0 mm thick, similar to the thickness of human nails, were placed on the surface of agar plates seeded with an inoculum of Trichophyton mentagrophytes standardized to a concentration of 2 ϫ 10 5 to 5 ϫ 10 5 conidia/ml as previously described (6). Three hundred microliters of a marketed 2% (wt/wt) miconazole nitrate or 8% (wt/wt) ciclopirox topical formulation was then applied to the surface of the hoof disc for 30 or 60 min. Plates were incubated for 4 days, and zones of inhibition (ZOI) were subsequently measured. As expected, the untreated controls showed no ZOI, while discs treated with miconazole nitrate 2% (wt/wt) following 60 min of exposure showed significantly larger ZOI than those exposed to 8% (wt/wt) ciclopirox nail lacquer (26.5 Ϯ 9.7 and 2.8 Ϯ 3.4 mm, respectively; P Յ 0.05).TurChub ZOI model. The TurChub ZOI assay used a modified static diffusion cell in which sections of human nail serve as the barrier through which the drug initially penetrates prior to reaching an agar-filled receptor chamber. Three penetrationenhancing formulations, supplied by Humco Pharmaceuticals (Austin, TX, USA) and containing a novel base formulation (comprised of acetylcysteine, alcohol, camphor, EDTA, eucalyptus oil, hydroxypropyl cellulose, hydroxypropyl starch phosphate, magnesium aluminum silicate, menthol, propylene carbonate, propylene glycol, purified water, sodium hydroxide, sodium thioglycolate, strontium chloride, tea tree oil, thymol, and urea), were tested. One formulation was a placebo comprised of the base formulation only, while the other two formulations contained either 10% (wt/wt) fluconazole or 10% (wt/wt) miconazole. Two marketed products, 8% (wt/wt) ciclopirox topical solution and 10% (wt/wt) efinaconazole solution, were also investigated.

No abstract

The application of thermal energy to enhance the percutaneous absorption of drugs offers an encouraging prospect for overcoming the skin barrier. External membranes such as the skin present a considerable barrier to the permeation of drugs, limiting the types of treatment that can be given via this route. These barrier properties are mostly dependent on the stratum corneum (SC), the outermost layer of skin, which in most cases is known to be the rate limiting step for drug diffusion across the skin.