• Title, Summary, Keyword: itraconazole

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Enhanced Bioavailability of Itraconazole in Liquid Preparation (난용성 항진균제 이트라코나졸의 액상제제화에 의한 생체이용율 개선)

  • Hwang, Woo-Sin;Kwon, Kwang-Il;Bang, Kyu-Ho
    • YAKHAK HOEJI
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    • v.44 no.6
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    • pp.528-533
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    • 2000
  • This study was to develop an effective itraconazole liquid preparation which exhibits an enhanced bioavailability. The solubility of itraconazole was increased (72-fold) in itraconazole liquid preparation as compared with itraconazole powder. The dissolution rate of itraconazole was higher for itraconazole liquid preparation filled into a hard gelatin capsule with 90% release within 20 min as compared to 55% for $Sporanox^{\circledR}$capsules. The oral absorption of itraconazole liquid preparation and $Sporanox^{\circledR}$tablets were studied in the rat. The area under the concentration-time curve $(AUC_{0-24hr})$ of itraconazole liquid preparation ($90.25\;{\pm}\;8.36\;{\mu}g{\cdot}hr/ml$) increased by 6.2 times compared to that of Sporanox tablets ($14.58\;{\pm}\;1.26\;{\mu}g{\cdot}hr/ml$) after oral administration of itraconazole 15 mg/rat each. $C_{max}$ also increased to $6.87\;{\pm}\;1.15\;{\mu}g/ml$ after administration of liquid preparation $1.58\;{\pm}\;0.16\;{\mu}g/ml$ of $Sporanox^{\circledR}$tablets. These results indicate that in vivo bioavailability of itraconazole liquid preparation was significantly enhanced as compared with $Sporanox^{\circledR}$tablets.

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The Microsponge Delivery System of Itraconazole: Preparation, Characterization and Release Studies (이트라코나졸 마이크로스폰지의 약물 전달 시스템: 제조, 특성 및 방출 연구)

  • Cho, Young-Ho;Lee, Jong-Hwa;Kim, Hak-Hyung;Lee, Gye-Won
    • KSBB Journal
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    • v.26 no.3
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    • pp.217-222
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    • 2011
  • Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. To improve the oral absorption and dissolution of poorly water-soluble itraconazole, microsponge system composed of $Eudragit^{(R)}$ E100 and polyvinyl alcohol(PVA) formulated by quasi-emulsion solvent diffusion method, and its physicochemical properties and pharmacokinetic parameters of itraconazole were studied. The microsponge of itraconazole were discrete free flowing micro sized particles with perforated orange peel like morphology as visualized by scanning electron microscope (SEM). Results showed that the drug loading efficiency, production yield, and particle size of itraconazole microsponge were affected by drug to polymer ratio, the volume of internal phase containing methylene chloride, stirring rate and the concentration of PVA used. Also, the results showed that the dissolution rate of itraconazole from the microsponges was affected by drug to polymer ratio. In other words, the release rate of itraconazole from microsponges was increased from at least 27.43% to 64.72% after 2 h. The kinetics of dissolution mechanism showed that the dissolution data followed Korsmeyer-Peppas model. Therefore, these results suggest that microsponge system can be useful for the oral delivery of itraconazole by manipulating the release profile.

Characterization of Itraconazole Semisolid Dosage Forms Prepared by Hot Melt Technique

  • Shim, Sang-Young;Ji, Chang-Won;Sah, Hong-Kee;Park, Eun-Seok;Lee, Beom-Jin
    • Archives of Pharmacal Research
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    • v.29 no.11
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    • pp.1055-1060
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    • 2006
  • The objective of this study was to formulate itraconazole semisolid dosage forms and characterize their physicochemical properties. Itraconazole and excipients such as polysorbate 80, fatty acids, fatty alcohols, oils and organic acids were melted at $160^{\circ}C$. The fused solution was then cooled immediately at $-10^{\circ}C$ to make wax-like semisolid preparations. Their physicochemical attributes were first characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectrometry. The solubility of itraconazole in semisolid preparations and their dispersability in the simulated gastric fluid were also determined. Our semisolid preparations did not show any distinct endothermic peak of a crystalline form of itraconazole around $160-163^{\circ}C$. This suggested that it was changed into amorphous one, when it was formulated into semisolid preparations. In addition, the distinctive functional peaks and chemical shifts of itraconazole were well retained after processing into semisolid preparations. It could be inferred from the data that itraconazole was stable during incorporation into semisolid preparations by the hot melt technique. In particular, itraconazole semisolid preparations composed of polysorbate 80, fatty acids and organic acids showed good solubility and dissolution when dispersed in an aqueous medium. It was anticipated that the semisolid dosage forms would be industrially applicable to improving the bioavailability of poorly water-soluble drugs.

Formulations of Itraconazole for Topical Skin Delivery (국소 피부 투여를 위한 이트라코나졸 제제의 조성)

  • Lee, Eun-A;Heo, Sung-Koun;Choi, Myeong-Jun;Chung, Suk-Jae;Shim, Chang-Koo;Kim, Dae-Duk
    • Journal of Pharmaceutical Investigation
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    • v.37 no.3
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    • pp.167-171
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    • 2007
  • Itraconazole is one of the most potent antifungal agents available in the market today. However, the low bioavailability due to its poor-water solubility calls for an alternative formulation to the current oral type. A topical itra-conazole-containing formulation may be of use for several reasons including the opportunity to reduce adverse events and generate high local tissue levels, more rapid drug delivery, and lower systemic exposure. The purpose of the present study was to investigate the vehicles for topical skin delivery of itraconazole. The effect of formulations on the hairless mouse skin permeation and deposition of itraconazole was determined using Franz diffusion cells at $37^{\circ}C$. Benzyl alcohol in micro-emulsion significantly increased the solubility of itraconazole, thereby increasing the skin permeation rate. However, lipo-some formulation showed the lowest solubility and permeation rate of itraconazole. Although the solubility of itraconazole in hydrogel formulation was lower than that in microemulsion, skin permeation rate was significantly higher probably due to its adhesive property. Therefore, microemulsion-based hydrogel formulation is expected to synergistically increase the skin permeation rate and skin deposition of itraconazole.

Interspecies Comparison of the Oral Absorption of Itraconazole in Laboratory Animals

  • Yoo, Sun-Dong;Kang, Eun-Hee;Shin, Beom-Soo;Lee, Hun-Jun;Lee, Sang-Heon;Lee, Kang-Choon;Lee, Kyu-Hyun
    • Archives of Pharmacal Research
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    • v.25 no.3
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    • pp.387-391
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    • 2002
  • The oral absorption and disposition of itraconazole were studied in rats, rabbits and dogs. Serum levels of itraconazole and its active metabolite, hydroxyitraconazole, were determined by a validated HPLC method. The absorption of itraconazole was relatively rapid in rats and dogs but was slower in rabbits. The terminal elimination half-life ($T_{1/2,{\lambda}z}$), time to the peak concentration ($T_{max}$), dose and weight normalized area under the curve (AUC) and the peak concentration ($C_{max}$) of itraconazole found in the dog were comparable to those reported in humans. As in humans, the metabolite to parent drug AUC ratios in rats and dogs were greater than unity but was less in rabbits. The dog appears to be an appropriate animal model while the rat, not the rabbit, may be used as an alternative animal model in predicting the oral absorption of itraconazole in humans.

Absorption of Itraconazole from Rat Small Intestine (이트라코나졸의 랫트 소장으로부터의 흡수)

  • Kim, Young-Hwa;Lee, Yong-Suk;Park, Gee-Bae;Lee, Kwang-Pyo
    • Journal of Pharmaceutical Investigation
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    • v.21 no.4
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    • pp.215-222
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    • 1991
  • The absorption characteristics of itraconazole, which is an antifungal agent, from intestinal segments in the anesthetized rat i1l situ were investigated in order to design an effective oral drug delivery system. The pH-solubility profile of itraconazole, the rate and extent of absorption of itraconazole, the optimal absorption site(s) of itraconazole and the absorption enhancing effect of sodium cholate on itraconazole were examined in the present study. In situ single-pass perfusion method and recirculating perfusion technique using duodenum(D), jejunum(J) and ileum(I) were employed for the calculation of apparent permeability(Pe) and apparent first-order rate constant(Kobs). respectively. The results of this study were as follows; (1) Itraconazole showed appreciable aqueous solubility only at pH values of below 2.0. (2) pe(cm/sec) decreased in the following order: $D(10.24{\pm}1.78{\times}10^{-4})>J(8.86{\pm}0.79{\times}10^{-4})>I(3.78{\pm}0.13 X 10^{-4})$. (3) $Kobs(min^{-1})$ decreased in the following order: $J(17.12{\pm}3.19{\times}10^{-3})>D(13.37{\pm}0.6{\times}10^{-3})>I(11.05{\pm}0.91{\times}10^{-3})$. (4) The solubility of itraconazole markedly increased with the increase of the concentration of sodium cholate. (5) The addition of 10 mM sodium cholate significantly increased the apparent first-order rate constant of itraconazole in the ileum by a factor of 6.8.

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Study of a Supercritical Fluid Process for the Preparation of Hydroxypropyl-β-cyclodextrin Inclusion Complexes (Hydroxypropyl-β-cyclodextrin 포접복합체 제조를 위한 초임계유체 공정 연구)

  • Lee, Sang-Yun;Kim, Jeong-Kyu;Kim, Woo-Sik;Ryu, Jong-Hoon;Lim, Gio-Bin
    • Korean Chemical Engineering Research
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    • v.43 no.1
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    • pp.110-117
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    • 2005
  • In this work, solid-state inclusion complex powders of itraconazole and $2-hydroxypropyl-{\beta}-cyclodextrin(HP-{\beta}-CD)$ were produced by a supercritical anti-solvent (SAS) process. In order to evaluate the degree of complexation, the thermal behavior of the microparticulate complexes was investigated using differential scanning calorimetry. The experimental results obtained for the solubility and dissolution rate of the microparticulate inclusion complexes in a buffer solution of pH 1.2 showed that the complexation of itraconazole with $HP-{\beta}-CD$ results in a significant increase in the solubility and dissolution rate of itraconazole. The particle size of the SAS-produced inclusion complexes was dramatically reduced ($<0.1-0.5{\mu}m$) compared with untreated itraconazole ($30-50{\mu}m$) and $HP-{\beta}-CD$ ($50-100{\mu}m$). The solubility of itraconazole was increased with the increase of pressure at a constant temperature to ca. $758.6{\mu}g/mL$ in an aqueous medium of pH 1.2. The dissolution rate of itraconazole was observed to be significantly improved and about 90% of itraconazole was found to be dissolved within 5-10 min.

A Highly Efficient Synthesis of Itraconazole Intermediates and Their Analogues (Itraconazole 중간체의 효율적 합성법과 그 유사체의 합성)

  • Ahn, Chong Il;Myoung, Young Chan;Choi, Ha Young;Kim, Seung Jin
    • Journal of the Korean Chemical Society
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    • v.43 no.6
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    • pp.676-681
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    • 1999
  • Itraconazole is an important drug for oral treatment of histoplasmosis and blastomycosis. ltraconazole has been the targets of many synthetic efforts due to their diverse antifungal activities. ln this study, an efficient synthetic route for Itraconazole intermediates has been developed using new procedures. Also, ltraconazole analogues introducing 2- and 3-methoxy group instead of ltraconazole intermediates with 4-methoxy group were synthesized.

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Efficacy of itraconazole in 18 cases of Malassezia dermatitis in dogs (개에서 Malassezia 피부염에 대한 itraconazole 치료 18례)

  • Jeong A-young;Hoh Woo-phil;Jeong Hyo-hoon;Eom Ki-dong;Lee Keun-woo;Oh Tae-ho
    • Journal of Veterinary Clinics
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    • v.22 no.2
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    • pp.90-93
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    • 2005
  • Itraconazole was found to be an effective antifungal for the treatment of canine Malassezia dermatitis (MD). MD was diagnosed in 18 dogs, which were treated with itraconazole administered orally at 5 mg/kg of body weight, q12hrs, for 21 to 30 days. High prevalence breeds of MD were Maltese $(22\%)$, Cocker Spaniel $(17\%)$, Pekingese $(11\%)$, and Vizsla $(11\%)$. The dermatological signs of Malassezia dermatitis were crust $(31\%)$, alopecia $(25\%)$, hyperpigmentation $(25\%)$, scales$(19\%)$, erythema $(13\%)$, lichenification $(11\%)$, pustule $(11\%)$, ear swelling$(11\%)$, papules $(5\%)$, and offensive odor $(5\%)$. Commonly affected areas were ear canal $(41\%)$, axillae $(18\%)$, groin $(15\%)$, perianal $(12\%)$, ventral aspect of the neck $(9\%)$, interdigital spaces$(1\%)$, and muzzle $(1\%)$. Sixty seven percent of dogs with MD had cocci. Clinical responses of itraconazole were seen good, moderate, no responses of itraconazole, in $89\%,\;0\%,\;and\;11\%$, respectively, according to the owner's satisfaction to follow up call. Recurrence was detected on five good responsive dogs and adverse effects of the treatment were detected in only one dog. On the basis of this clinical study, itraconazole is a good choice in the treatment of canine Malassezia dermatitis. Efficacy, frequency of administration and veterinary approval are the major advantages.

Preparation and Characterization of Solid Dispersions of Itraconazole by using Aerosol Solvent Extraction System for Improvement in Drug Solubility and Bioavailability

  • Lee, Si-Beum;Nam, Kyung-Wan;Kim, Min-Soo;Jun, Seoung-Wook;Park, Jeong-Sook;Woo, Jong-Soo;Hwang, Sung-Joo
    • Archives of Pharmacal Research
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    • v.28 no.7
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    • pp.866-874
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    • 2005
  • The objective of this study was to elucidate the feasibility to improve the solubility and bioavailability of poorly water-soluble itraconazole via solid dispersions by using supercritical fluid (SCF). Solid dispersions of itraconazole with hydrophilic polymer, HPMC 2910, were prepared by the aerosol solvent extraction system (ASES) under different process conditions of temperature/pressure. The particle size of solid dispersions ranged from 100 to 500 nm. The equilibrium solubility increased with decrease (15 to 10 MPa) in pressure and increase (40 to $60^{\circ}C$) in temperature. The solid dispersions prepared at $60^{\circ}C$/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at $60^{\circ}C$/10MPa showed approximately 610-fold increase and no endothermic peaks corresponding to pure itraconazole were observed, indicating that itraconazole might be molecularly dispersed in HPMC 2910 in the amorphous form. The amorphous state of itraconazole was confirmed by DSC/XRD data. The pharmacokinetic parameters of the ASES-processed solid dispersions, such as $T_{max},\;C_{max},\;and\;AUC_{0-24h}$ were almost similar to $Sporanox_{\circledR}$ capsule which shows high bioavailability. Hence, it was concluded that the ASES process could be a promising technique to reduce particle size and/or prepare amorphous solid dispersion of drugs in order to improve the solubility and bioavailability of poorly water-soluble drugs.