Diversity in Itraconazole Cocrystals with Aliphatic Dicarboxylic Acids of Varying Chain Length

Shevchenko, Anna; Miroshnyk, Inna; Pietilä, Lars‐Olof; Haarala, Jorma; Salmia, Jukka; Sinervo, Kai; Mirza, Sabiruddin; Veen, Bert van; Kolehmainen, Erkki; Nonappa, Nonappa; Yliruusi, Jouko

doi:10.1021/cg401061t

Cited by 49 publications

(44 citation statements)

References 49 publications

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“…In the co-crystal spectrum, the peak was observed as a result of the interaction between the drug and the counter (the synthon), which were not seen for the single drug and the counter. As discussed in previous study, 26) the peak was derived from the carbonyl group of COOH in FA, which was shifted to a higher wavenumber by an interaction between OH of COOH in FA and 1, 2, 4-triazole group in ITZ, from 1687 cm −1 (on single FA) to 1720 cm −1 (on co-crystal and co-amorphous).…”

Section: Characterization Of the Itz Co-amorphous Compoundssupporting

confidence: 59%

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

Yamamoto

Kojima

Karashima

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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To judge the developability and analyze functional mechanism of co-amorphouses, we investigated the physicochemical properties of co-amorphouses and compare the properties with the co-crystals having the same drug and counters. Co-amorphous compounds are a novel approach to improve the physicochemical properties of drugs. A co-amorphous is in an amorphous solid state allowing non-ionic interactions between drug molecules and counter molecules. The co-amorphous compounds composed of itraconazole (ITZ) with the organic carboxyl acid, fumaric acid (FA) or L-tartaric acid (TA), were prepared by mechanical grinding. Potential interactions within ITZ-FA co-amorphous were assessed by Raman spectroscopy. ITZ-FA coamorphous was not crystallized as the co-crystal or as a single ITZ crystal, suggesting that the amorphous state, like the amorphous solid dispersion, was physically stable and that ITZ-FA co-amorphous was also chemically stable. In contrast, no clear interactions were observed within ITZ-TA co-amorphous, and the coamorphous was physically stable but chemically unstable. The solubility of the co-amorphous state was much higher than those of ITZ crystal and the co-crystals and was almost identical to that of amorphous ITZ. A co-amorphous compound like ITZ-FA co-amorphous might be feasible to implement in the development of solid drug products and bring some merits compared to the co-crystals, and the function is governed by the interaction between a drug and a counter. The co-amorphous approach may be an effective strategy for drug development and can contribute to the production of novel drugs with improved functions.Key words co-amorphous; co-crystal; stability; solubilization; interaction; itraconazole Solubility improvement is one of the most important challenges for drug development of poorly soluble drugs. Amorphization of drugs is a major effective strategy to prepare solubilized formulations, because the crystal packing effect on a drug substance significantly decreases its solubility. 1-3)An amorphous compound is in a higher energy state and has a higher mobility than a crystalline compound, improving its solubility and dissolution properties. However, due to the higher energy state, the physical and chemical stability of amorphous compounds are relatively lower than those of a crystal. 4,5) In many cases, an amorphous drug is formulated by solid dispersion with hydrophilic polymers to improve the amorphous drug stability. [6][7][8] The complex formed with polymers can prevent the drug's crystallization and maintain the physical stability of the amorphous state. Generally, weak interactions cannot sufficiently stabilize amorphous drugs. 9)The prediction and design leading to the interactions between the drug and the polymer are still difficult to accomplish. Therefore, solid dispersions combined with several kinds and amounts of polymers need to be tested.As another approach to enhance a drug's solubility, pharmaceutical co-crystals have been investigated and adapted to the drug development processes in...

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Section: Characterization Of the Itz Co-amorphous Compoundssupporting

confidence: 59%

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

Yamamoto

Kojima

Karashima

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…17) It has been reported that in the solid dispersion, the drug is dispersed in the polymer matrix at the molecular level and forms an interaction, such as hydrogen bonding, between drug and polymer, thereby increasing the T g of the polymer. 18) In addition, interaction occurs between the triazole group of ITCZ and the carboxyl group of dicarboxylic acids, as described in a previous report. 19) Therefore, the interaction between chemical bonds of ITCZ and PLGA in ITCZ-PLGA MS was examined by FT-IR.…”

Section: Resultsmentioning

confidence: 66%

“…18) In addition, interaction occurs between the triazole group of ITCZ and the carboxyl group of dicarboxylic acids, as described in a previous report. 19) Therefore, the interaction between chemical bonds of ITCZ and PLGA in ITCZ-PLGA MS was examined by FT-IR.…”

Section: Resultsmentioning

confidence: 66%

Preparation and Characterization of Itraconazole- or Miconazole-Loaded PLGA Microspheres

Matsuura

Kojima

Haraguchi

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres (MS) loaded with itraconazole (ITCZ) or miconazole (MCZ) under different evaporation temperatures (25 or 40°C) using an oil-in-water emulsion solvent evaporation method in order to evaluate the initial burst release of drug. Loading efficiencies were comparatively good and the diameters of prepared drug-loaded PLGA MS were around 20 µm in all formulations. The release rates of ITCZ-PLGA MS prepared at 40°C showed a significantly restricted release profile compared with the corresponding ITCZ-PLGA MS prepared at 25°C. This difference in release rate of ITCZ was thought to be caused by the self-healing effect of PLGA, as the glass transition temperature of PLGA is around 40°C. With respect to the MCZ-PLGA MS, the initial burst release was similar in formulations prepared at both 25 and 40°C. Scanning electron microscope results suggested that the initial burst release was due to the localization of MCZ on the surface of MCZ-PLGA MS at higher concentrations. Differential scanning calorimetry measurements suggested complete amorphization of MCZ in MCZ-PLGA MS, whereas crystalline ITCZ was detected in the ITCZ-PLGA MS. This complete amorphization of MCZ is considered to be one of the reasons for the initial burst release.

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“…The formation of ITZ ditosylate salt with enhanced solubility and dissolution rate has also been studied by Kumar et al [24]. Futhermore, ITZ cocrystals with oxalic, adipic, malonic, glutaric and pimelic acids were successfully synthesized by other researchers [25].…”

Section: Introductionmentioning

confidence: 98%

Solid-State Properties and Solubility Studies of Novel Pharmaceutical Cocrystal of Itraconazole

Hiendrawan¹,

Veriansyah²,

Tjandrawinata³

2018

Int J App Pharm

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Objective: Pharmaceutical cocrystal is a promising method to improve the solubility of active pharmaceutical ingredients (APIs). Itraconazole (ITZ) is a BCS class II antifungal drug with poor aqueous solubility, therefore an attempt was made to improve the solubility of ITZ using cocrystallization technique. In this work, six novel pharmaceutical cocrystals of ITZ with various coformers, including 4-hydroxybenzoic acid (4HBA), trans-cinnamic acid (TCA), suberic acid (SUB), sebacic acid (SBC), 1-hydroxy-2-naphthoic acid (1H2N), and benzamide (BZD) were prepared.Methods: ITZ cocrystals was prepared by solvent evaporation process. The cocrystals produced were characterized using powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and fourier transform infrared (FTIR) spectroscopy. Solubility analysis was performed to evaluate the cocrystals.Results: PXRD and DSC analysis revealed that the pattern of all ITZ cocrystals was distinguishable from the individual compounds which indicates the formation of new phase. The solubility of ITZ and its cocrystals from highest to lowest after 24 h in 0.1 N HCl solution (pH 1.2) follows the order ITZ-TCA (1.97-fold), ITZ-SBC (1.09-fold), ITZ, ITZ-1H2N (0.58-fold) and ITZ-4HBA (0.46-fold).Conclusion: This study demonstrates that the selection of coformers has pronounced an impact on the physicochemical properties of ITZ. Based on this study, it can be concluded that cocrystallization offers a valuable way to improve the solubility of ITZ.

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Diversity in Itraconazole Cocrystals with Aliphatic Dicarboxylic Acids of Varying Chain Length

Cited by 49 publications

References 49 publications

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

Preparation and Characterization of Itraconazole- or Miconazole-Loaded PLGA Microspheres

Solid-State Properties and Solubility Studies of Novel Pharmaceutical Cocrystal of Itraconazole

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