Characterization and pharmacokinetic study of itraconazole solid dispersions prepared by solvent-controlled precipitation and spray-dry methods

Sim, Taehoon; Lim, Chaemin; Lee, Junwon; Kim, Dong Wuk; Kim, Young-Sam; Kim, Minsoo; Choi, Sun Ha; Choi, Han‐Gon; Lee, Eun Seong; Kim, Kil-Soo; Kang, Wonku; Oh, Kyung Taek

doi:10.1111/jphp.12805

Cited by 9 publications

(6 citation statements)

References 46 publications

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“…Crystalline itraconazole displayed characteristic XRPD diffraction peaks at 14.7°, 17.5°, 20.8°, 24°, 25.8°, and 27.5° 2

( Figure 3 A), consistent with form 1 as reported elsewhere [ 46 , 47 ]. Formation of amorphous itraconazole post quench cooling was confirmed by the presence of a broad halo in the XRPD diffractogram, with no characteristic Bragg’s diffraction peaks corresponding with the crystalline form ( Figure 3 A).…”

Section: Resultssupporting

confidence: 85%

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

et al. 2022

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Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC -L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R2 = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care.

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“…Crystalline itraconazole displayed characteristic XRPD diffraction peaks at 14.7°, 17.5°, 20.8°, 24°, 25.8°, and 27.5° 2

Section: Resultssupporting

confidence: 85%

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

et al. 2022

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“…For the dissolution profiles during acidic-to-neutral pH transition, the pure lutein or lutein-loaded solid dispersions were exposed to the gastric fluid (n=3). After 2 h, concentrated PBS solution with Tween 80 was added into the dissolution media and pH was adjusted to 6.8 to make the artificial intestinal fluid condition (22).…”

Section: In Vitro Dissolution Ratementioning

confidence: 99%

“…On the contrary, HPMCAS-LF-based solid dispersions can be rapidly disintegrated under intestinal conditions due to the repulsive force of the ionized succinyl group of the polymer, thus possibly accelerating drug release in an amorphous state (22,45). Therefore, to investigate the impact of the formulation on the dissolution profile of lutein, we conducted dissolution studies under simulated gastric and intestinal conditions with a USP apparatus 2.…”

Section: Characterization Of Lutein-loaded Solid Dispersionsmentioning

confidence: 99%

“…1). Displaying low solubility under acidic conditions, HPMCAS-LF could protect lutein from degradation under gastric conditions while allowing rapid release of lutein under intestinal conditions through the repulsive force of its succinyl group (22,23). Thus, the incorporation of lutein in HPMCAS-LF solid dispersions could significantly increase its bioavailability by impeding its exposure to acids in the stomach and by promoting its release in an amorphous form in the intestine.…”

Section: Introductionmentioning

confidence: 99%

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Preparation and Characterization of a Lutein Solid Dispersion to Improve Its Solubility and Stability

et al. 2021

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Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solventcontrolled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.

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“…Various polymers have been employed as peptide carriers in diabetes, oncology, and cardiovascular drugs [11]. Solid dispersion is an increasingly popular method that uses hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and polymer micelles as carriers for insoluble drugs [12,13]. Glucosamine hydrochloride has been used in solid dispersions [14] and hydrophobic molecules have been included in cyclodextrin [15] to enhance dissolution rates.…”

Section: Introductionmentioning

confidence: 99%

Controlling the Dissolution Rate of Hydrophobic Drugs by Incorporating Carbon Nanotubes with Different Levels of Carboxylation

Mitra

2019

Applied Sciences

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We present the anti-solvent precipitation of hydrophobic drugs griseofulvin (GF) and sulfamethoxazole (SMZ) in the presence of carboxylated carbon nanotubes (f-CNTs). The aqueous dispersed f-CNTs were directly incorporated into the drug particles during the precipitation process. f-CNTs with different levels of carboxylation were tested where the hydrophilicity was varied by altering the C:COOH ratio. The results show that the hydrophilic f-CNTs dramatically enhanced the dissolution rate for both drugs, and the enhancement corresponded to the hydrophilicity of f-CNTs. The time to reach 80% dissolution (t80) reduced from 52.5 min for pure SMZ to 16.5 min when incorporated f-CNTs that had a C:COOH ratio of 23.2 were used, and to 11.5 min when the ratio dropped to 16. A corresponding decrease was observed for SMZ for the above-mentioned f-CNTs.The study clearly demonstrates that it is possible to control the dissolution rate of hydrophobic drugs by altering the level of carboxylation of the incorporated CNTs.

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Characterization and pharmacokinetic study of itraconazole solid dispersions prepared by solvent-controlled precipitation and spray-dry methods

Abstract: This study suggests that the SCPM method can be widely used for solid dispersion preparations due to improved dissolution and PK profile.

Cited by 9 publications

References 46 publications

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

Preparation and Characterization of a Lutein Solid Dispersion to Improve Its Solubility and Stability

Controlling the Dissolution Rate of Hydrophobic Drugs by Incorporating Carbon Nanotubes with Different Levels of Carboxylation

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