Single-Step Preparation and Deagglomeration of Itraconazole Microflakes by Supercritical Antisolvent Method for Dissolution Enhancement

Sathigari, Sateesh Kumar; Ober, Courtney A.; Sanganwar, Ganesh P.; Gupta, Ram B.; Babu, R. Jayachandra

doi:10.1002/jps.22524

Cited by 20 publications

(5 citation statements)

References 58 publications

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“…However, all of the distinct peaks disappeared in the SD particles’ diffractogram, which indicated that the crystal form did not exist in the SD particles. 28 This result suggested that ITZ might exist in the amorphous state in SD particles, as frequently observed for SDs.…”

Section: Resultssupporting

confidence: 55%

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Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

Yin

Daintree²,

Ding³

et al. 2015

DDDT

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This research aimed to develop a supercritical fluid (SCF) technique for preparing a particulate form of itraconazole (ITZ) with good dissolution and bioavailability characteristics. The ITZ particulate solid dispersion was formulated with hydroxypropyl methylcellulose, Pluronic F-127, and L-ascorbic acid. Aggregated particles showed porous structure when examined by scanning electron microscopy. Powder X-ray diffraction and Fourier transform infrared spectra indicated an interaction between ITZ and excipients and showed that ITZ existed in an amorphous state in the composite solid dispersion particles. The solid dispersion obtained by the SCF process improved the dissolution of ITZ in media of pH 1.0, pH 4.5, and pH 6.8, compared with a commercial product (Sporanox®), which could be ascribed to the porous aggregated particle shape and amorphous solid state of ITZ. While the solid dispersion did not show a statistical improvement (P=0.50) in terms of oral bioavailability of ITZ compared with Sporanox®, the Cmax (the maximum plasma concentration of ITZ in a pharmacokinetic curve) of ITZ was raised significantly (P=0.03) after oral administration. Thus, the SCF process has been shown to be an efficient, single step process to form ITZ-containing solid dispersion particles with good dissolution and oral bioavailability characteristics.

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Section: Resultssupporting

confidence: 55%

“… 12 , 23 , 24 Meanwhile, some studies also reported the use of SCF technology to obtain nanoscale-level SD particles or drug–polymer aggregates to improve the solubility and oral bioavailability of ITZ. 27 , 28 …”

Section: Introductionmentioning

confidence: 99%

Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

Yin

Daintree²,

Ding³

et al. 2015

DDDT

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“…Despite the cocrystals produced by each method having similar crystal and chemical structures as determined by PXRD and FTIR, it appears that morphological and compositional differences resulting from the method of preparation can have a strong effect on drug dissolution. Both methods of cocrystal preparation gave thin flakes, a morphology previously observed in itraconazole crystallization (46). The flakes, characterized by a length, width, and height, cannot be sized by conventional means (light scattering) and determining a particle size distribution would have little value.…”

Section: Dissolution Enhancement By Gas Cocrystallizationmentioning

confidence: 91%

“…Furthermore, since the particles are not submicron, particle size is not expected to have a significant influence on the dissolution rate. Based on a prior publication (46) in which the specific surface area of ∼20×5×1 μm (l × w × h) itraconazole flakes was determined, it is expected that the cocrystal products produced by both methods would have nearly identical specific surface areas of ∼2 m 2 /g. Therefore, it is not expected that particle size or surface area is responsible for the enhanced dissolution of the itraconazole-succinic acid cocrystals produced by GAS cocrystallization.…”

Section: Dissolution Enhancement By Gas Cocrystallizationmentioning

confidence: 99%

Formation of Itraconazole–Succinic Acid Cocrystals by Gas Antisolvent Cocrystallization

Ober

Gupta

2012

AAPS PharmSciTech

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Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO(2) to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO(2), which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole-succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole-succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO(2) antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole-succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO(2) to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.

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“…Fumed silica, an inert carrier, has extremely low bulk density, high surface area and specific porous configuration 13,14 . It can be used as a stable adsorption carrier for drug particles by supercritical fluid CO 2 technique 15 . In order to improve the bioavailability of SP, SP was cosolubilized in supercritical fluid CO 2 , and then SP was impregnated into the fumed silica when CO 2 was removed.…”

Section: Introductionmentioning

confidence: 99%

In-vitroandin-vivostudy of amorphous spironolactone prepared by adsorption method using supercritical CO₂

Jiang

et al. 2013

Drug Development and Industrial Pharmacy

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Single-Step Preparation and Deagglomeration of Itraconazole Microflakes by Supercritical Antisolvent Method for Dissolution Enhancement

Cited by 20 publications

References 58 publications

Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

Formation of Itraconazole–Succinic Acid Cocrystals by Gas Antisolvent Cocrystallization

In-vitroandin-vivostudy of amorphous spironolactone prepared by adsorption method using supercritical CO₂

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Single-Step Preparation and Deagglomeration of Itraconazole Microflakes by Supercritical Antisolvent Method for Dissolution Enhancement

Cited by 20 publications

References 58 publications

Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

Formation of Itraconazole–Succinic Acid Cocrystals by Gas Antisolvent Cocrystallization

In-vitroandin-vivostudy of amorphous spironolactone prepared by adsorption method using supercritical CO2

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In-vitroandin-vivostudy of amorphous spironolactone prepared by adsorption method using supercritical CO₂