Solid dispersions of itraconazole and enteric polymers made by ultra-rapid freezing

Overhoff, Kirk A.; Moreno, Alejandro; Miller, Dave A.; Johnston, Keith P.; Williams, Robert O.

doi:10.1016/j.ijpharm.2006.11.043

Cited by 84 publications

(57 citation statements)

References 31 publications

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“…The formation of this solid solution at a processing temperature approximately 40°C below the melt temperature of ITZ represents solubilization of ITZ by the molten polymer during processing and indicates excellent miscibility of ITZ with EUDRAGIT \ L 100-55. Miscibility of ITZ with EUDRAGIT \ L 100-55 was reported by Overhoff et al at levels greater than 60% (w/w) drug loading (19). Qualitative evaluation of ITZ solubility in TEC revealed little to no solubility of ITZ in TEC, and considering the 3:1 ratio of ITZ to TEC in the formulation, it is likely that TEC only facilitates the solubilization of ITZ by increasing the plasticity of EUDRAGIT \ L 100-55 at the processing temperature.…”

Section: Dsc Analysis Of Hme Processed Formulationsmentioning

confidence: 86%

Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption

et al. 2008

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Section: Dsc Analysis Of Hme Processed Formulationsmentioning

confidence: 86%

Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption

et al. 2008

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“…However, it has low aqueous solubility and high membrane permeability included in class 2 of Biopharmaceutical Drug Classification system (Amidon et al, 1995). Various oral formulations of itraconazole such as solid dispersions (Jung et al, 1999;Kipp, 2004;Overhoff et al, 2007), inclusion complex (Buchanan et al, 2007;Holvoet et al, 2007;Wempe et al, 2008), hot-melt extrusion and micellar formulation (Hong et al, 2006;Yi et al, 2007) were developed to improve the solubility and bioavailability of itraconazole.…”

Section: Introductionmentioning

confidence: 99%

Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability

Park

Xuan

et al. 2010

Arch. Pharm. Res.

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To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 microg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C(max) and T(max) compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.

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“…Citric acid was used as a solubilizer for sibutramine formulation. 13,14) The formula VI-VIII with citric acid greatly improved the solubility of drug compared to the formula III without citric acid (Fig. 1C).…”

Section: Preparation Of Sibutramine-loaded Solid Dispersionmentioning

confidence: 95%

“…4,8) However, sibutramine base with low solubility has not been used in commercial formulation. Various oral formulations of sibutramine such as another salt form such as sibutramine mesylate 9,10) and sibutramine tartrate, 11) solid dispersions with poloxamer [12][13][14] and inclusion complex. …”

mentioning

confidence: 99%

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Jang

Kang

et al. 2010

Biological & Pharmaceutical Bulletin

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Sibutramine [1-(4-chlorophynyl)-N,N-dimethyl-a-(2-methylpropyl)cyclobutane methane amine] is a newer antiobesity drug with a novel mechanism of action.1) It contains a potent inhibitor of the reuptake of noradrenaline (NA), serotonin (5-HT) and may stimulate thermogenesis by its activation of b 3 -adrenoceptors in brown adipose tissue. [2][3][4] In human subjects, sibutramine is rapidly metabolized to an Nmono-desmethyl metabolite (desmethylsibutramine [Metabolite I]) and an N,N-didesmethyl metabolite (didesmethylsibutramine [Metabolite II]). The in vivo effects of sibutramine are predominantly the results of the action of the above 2 metabolites. 4-7)Sibutramine hydrochloride monohydrate is the commercially available formulation of sibutramine with the relatively high solubility of 2.9 mg/ml at pH 5.2 and melting point of 190°C. 4,8) However, sibutramine base with low solubility has not been used in commercial formulation. Various oral formulations of sibutramine such as another salt form such as sibutramine mesylate 9,10) and sibutramine tartrate, 11) solid dispersions with poloxamer [12][13][14] and inclusion complex. 15)One of the well established method for increasing the solubility and bioavailability of poorly water-soluble drugs is solid dispersion.16) Several conventional methods such as melting, solvent evaporation and solvent wetting were reported to prepare solid dispersions. 17,18) However, the solid dispersion prepared by melting method with high temperature might chemically decompose the drugs. 19,20) In the case of solvent evaporation and solvent wetting method, the drug in the solid dispersions changed to amorphous form, resulting that the drug might be unstable. 18) Furthermore, a large amount of hydrophilic carriers against drug in these conventional solid dispersions must be needed to improve the solubility of poorly water-soluble drugs. 21,22) In this study, to improve the bioavailability of poorly water-soluble sibutramine base, various sibutramine baseloaded solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was then investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil ® ). This commercial product is a conventional capsule which contains 100 mg sibutramine hydrochloride monohydrate and is usually taken multiple times a day. Poloxamer has been employed to enhance the solubility and bioavailability of poorly water-soluble drugs. 19,23) HPMC is frequently used in the preparation of conventional pharmaceutical oral dosage form due to its hydrophilic and soft property. 24,25) To develop a novel sibutramine base-...

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Solid dispersions of itraconazole and enteric polymers made by ultra-rapid freezing

Cited by 84 publications

References 31 publications

Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption

Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption

Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

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