Itraconazole: an effective oral antifungal for onychomycosis

Jain, Sanchit; Sehgal, Virendra

doi:10.1046/j.1365-4362.2001.01039.x

Cited by 26 publications

(14 citation statements)

References 35 publications

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“…ITZ is a synthetic anti-fungal drug, which is composed of a 1:1:1:1 racemic mixture of four diastereomers (two enantiomeric pairs). Three chiral centers are present in each diastereomer which possess a molecular formula of C 35 H 38 C l2 N 8 O 4 and molecular weight of 705.64 g/mol (Grant and Clissol 1989;Jain and Sehgal 2001). ITZ is poorly soluble in aqueous media (less than 1 lg/mL in aqueous solutions at pHs of 1-12.7) with a partition coefficient [5 in octanol/water at pH 6.…”

Section: Introductionmentioning

confidence: 99%

Development of self emulsifying drug delivery system of itraconazole for oral delivery: formulation and pharmacokinetic consideration

Chudasama

Shah

Patel

et al. 2015

Journal of Pharmaceutical Investigation

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Poorly water-soluble drug, itraconazole (ITZ) offers a challenge in developing a drug product with adequate bioavailability. The potential for lipidic self-emulsifying drug delivery system to improve the oral bioavailability of ITZ was investigated in fasted rats. A series of ITZ SEDDS were prepared in three groups based on oil:S/CoS mixture ratios (1:9, 1:6 and 1:4) using Capryol 90 (oil), a mixture of Labrasol and Tween 20 (-surfactants) and Transcutol P (co-surfactant). The multicomponent delivery systems were optimized by evaluating their ability to self-emulsify when introduced in simulated gastric fluid, without pepsin, under gentle agitation and by determination of droplet size and visual observation. Three formulations (F5, F21 and F27), one from each group were selected based on droplet size and visual observation. The effect of oil and surfactants content on mean globule size of resulting emulsions was studied. It was clear that oil to surfactant and co-surfactant ratio has the main impact on the droplet size of the emulsion formed after dilution. However, the relation between droplet size and in vivo absorption of ITZ was futile. The order of AUC was 1:4 [ 1:6 [ 1.9 for oil:S/CoS mixture ratios. Following an oral administration of developed SEDDS and marketed capsule to rats, a 1.7, 2.0 and 2.33-fold increase in bioavailability was observed for F5, F21 and F27 respectively, compared with marketed capsule. The results from this study demonstrate the potential use of SEDDS to provide an effective way of improving oral absorption of lipophilic drugs.

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Section: Introductionmentioning

confidence: 99%

Development of self emulsifying drug delivery system of itraconazole for oral delivery: formulation and pharmacokinetic consideration

Chudasama

Shah

Patel

et al. 2015

Journal of Pharmaceutical Investigation

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“…[1][2][3] In addition, the drug has an interesting tissue distribution, which has made possible effective and rapid treatments of vaginal candidiasis when the drug is administered orally. [4][5][6] A topical itraconazole-containing formulation may be of use for several reasons including the opportunity to generate high local tissue levels, more rapid drug delivery, and lower systemic exposure.…”

Section: Introductionmentioning

confidence: 99%

A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole

et al. 2003

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KEYWORDSItraconazole, vaginal, cyclodextrin, mucoadhesive, toxicity, clinical investigation, candidiasisThe development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-ȕ-cyclodextrin (HPȕCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPȕCD. After pH adjustment, the itraconazole/HPȕCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPȕCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.

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“…At present, the oral antifungal agents griseofulvin (10), terbinafine (12), and itraconazole (9) are available for the treatment of tinea unguium because antifungal agents are generally ineffective when applied topically (13,23). The treatment of tinea unguium has improved following the introduction of terbinafine and itraconazole.…”

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confidence: 99%

Therapeutic Efficacy of Topically Applied KP-103 against Experimental Tinea Unguium in Guinea Pigs in Comparison with Amorolfine and Terbinafine

Tatsumi

Yokoo

Senda

et al. 2002

Antimicrob Agents Chemother

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The therapeutic efficacy of KP-103, a novel topical triazole, in a guinea pig tinea unguium model was investigated. Experimental tinea unguium and tinea pedis were produced by inoculation of Trichophyton mentagrophytes SM-110 between the toes of the hind paw of guinea pigs. One percent solution (0.1 ml) of KP-103, amorolfine, or terbinafine was topically applied to the nails and whole sole of an infected foot once daily for 30 consecutive days, and terbinafine was also orally administered at a daily dose of 40 mg/kg of body weight for 30 consecutive days, starting on day 60 postinfection. The fungal burdens of nails and plantar skin were assessed using a new method, which makes it possible to recover infecting fungi by removing a carryover of the drug remaining in the treated tissues into the culture medium. Topically applied KP-103 inhibited the development of nail collapse, significantly reduced the fungal burden of the nails, and sterilized the infected plantar skin. On the other hand, topical amorolfine and topical or oral terbinafine were ineffective for tinea unguium, although these drugs eradicated or reduced the fungal burden of plantar skin. The in vitro activities of amorolfine and terbinafine against T. mentagrophytes SM-110 were 8-and 32-fold, respectively, decreased by the addition of 5% keratin to Sabouraud dextrose broth medium. In contrast, the activity of KP-103 was not affected by keratin because its keratin affinity is lower than those of the reference drugs, suggesting that KP-103 largely exists in the nails as an active form that was not bound to keratin and diffuses in the nail without being trapped by keratin. The effectiveness of KP-103 against tinea unguium is probably due to its favorable pharmacokinetic properties in the nails together with its potent antifungal activity.

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Itraconazole: an effective oral antifungal for onychomycosis

Cited by 26 publications

References 35 publications

Development of self emulsifying drug delivery system of itraconazole for oral delivery: formulation and pharmacokinetic consideration

Development of self emulsifying drug delivery system of itraconazole for oral delivery: formulation and pharmacokinetic consideration

A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole

Therapeutic Efficacy of Topically Applied KP-103 against Experimental Tinea Unguium in Guinea Pigs in Comparison with Amorolfine and Terbinafine

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