Crystal Type Iof Azilsartan Polymorphs: Preparation and Analysis

Ge, Yuhua; Li, Tingting; Cheng, J.

doi:10.4236/jcpt.2016.61001

Cited by 9 publications

(13 citation statements)

References 3 publications

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“…The particle size and crystal form of a drug also affect pharmacological efficacy, due to their ability to alter the physicochemical properties of solubility, dissolution, and dosage forms. During the crystallization of a drug, different crystal structures can be formed, as the packing of molecules in space change at different temperatures, solutions, and pressures [14][15][16][17]. Generally, the appearance, melting point, dissolution, and other aspects of the same drug are significantly different in diverse crystal forms, which correspondingly affect clinical efficacy [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Studies on the Crystal Forms of Istradefylline: Structure, Solubility, and Dissolution Profile

Wang

Zheng

et al. 2022

Crystals

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Istradefylline as a selective adenosine A2A-receptor antagonist is clinically used to treat Parkinson’s disease and improve dyskinesia in its early stages. However, its crystal form, as an important factor in the efficacy of the drug, is rarely studied. Herein, three kinds of crystal forms of istradefylline prepared from ethanol (form I), methanol (form II), and acetonitrile (form III) are reported by use of a crystal engineering strategy. These three crystal forms were characterized and made into tablets for dissolution testing. Both the solubility and the dissolution rates were also determined. The dissolution rate of form I and form III is significantly higher than form II at pH 1.2 (87.1%, 58.2%, and 87.7% for form I, form II, and form III, respectively), pH 4.5 (88.1%, 58.9%, and 87.1% for form I, form II, and form III, respectively) and pH 6.8 (87.5%, 58.2%, and 86.0% for form I, form II, and form III, respectively) at 60 min. Considering the prepared solution and the proper dissolution profile, form I is anticipated to possess promising absorption for bioavailability.

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Section: Introductionmentioning

confidence: 99%

Studies on the Crystal Forms of Istradefylline: Structure, Solubility, and Dissolution Profile

Wang

Zheng

et al. 2022

Crystals

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“…It is reported that there are four kinds of crystalline forms of this chemical, − and the crystal form, size distribution, and polymorphism could influence its pharmaceutical quality and effectiveness . Despite sufficient studies on its polymorph, the solubility information of this drug has been ignored. Indeed, multiple solvents were applied in its crystallization and recrystallization process such as isopropanol, dimethylformamide, methanol, and acetonitrile.…”

Section: Introductionmentioning

confidence: 99%

Solubility of Azilsartan in Methanol, Ethanol, Acetonitrile, n-Propanol, Isopropanol, Tetrahydrofuran, and Binary Solvent Mixtures between 293.15 and 333.15 K

Kang

Qin

et al. 2020

ACS Omega

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A precise determination method of azilsartan solubility between 293.15 and 333.15 K in several ordinary solvents and some of their aqueous mixtures was established by high-performance liquid chromatography. In all tested solvents, its solubility shows exponential growth with the increase in temperature. This trend is especially pronounced in methanol and ethanol. The order of solubility of azilsartan can be expressed as ethanol > tetrahydrofuran > ethanol/water (8/2, v/v) > methanol > methanol/water (8/2, v/v) > n-propanol > isopropanol > ethanol/Water (5/5, v/v) > acetonitrile. The solubility data of azilsartan were well correlated by the λh model. Moreover, the thermodynamic data including the dissolving enthalpy, entropy, and Gibbs free energy of azilsartan in each solvent were calculated which is crucial to its preparation technology study.

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“…Among them, the stable polymorph is type I (P2 1 /C, Z = 4; a = 9.659 Å, b = 11.329 Å, c = 20.046 Å; β = 90.30°). 3 Because of the poor solubility of type I azilsartan crystals in water, improvement of the dissolution property is a major challenge to overcoming unsatisfactory drug efficacy. In general, the surface area of drug particles plays a role in determining their dissolution rate when wetted by luminal fluids, and therefore, reduction of their crystal size may be an effective way to dissolve the problem.…”

Section: Introductionmentioning

confidence: 99%

Crystallization of Azilsartan with Acidification of Azilsartan Disodium Salt

Kim

Koo

2019

Crystal Growth & Design

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A reactive crystallization process induced by acidification of azilsartan disodium salt was proposed to produce sub-micron-sized crystals. In the present work, azilsartan crystals were obtained by mixing two aqueous solutions of azilsartan disodium salt (ADS solution) and acetic acid (AA solution). When ADS solution was injected into AA solution, the crystalline azilsartan (type I), the thermodynamically stable form, could be obtained by the phase transformation of amorphous intermediates of azilsartan initially precipitated. Azilsartan crystals transformed from amorphous phase were found to be much smaller than those obtained directly with no transformation by addition of AA solution into ADS solution. The spectra of ATR-FTIR and particle counts from the focused beam reflectance measurement (FBRM) were utilized to investigate the effect of temperature on the transformation process. Final crystal size of azilsartan was found to be influenced by the relative scale of dissolution time for amorphous intermediates. Furthermore, the recovery of azilsartan crystals was found to be strongly affected by the final pH of mixed suspension. Finally, azilsartan crystals with size of about 500 nm and the recovery of higher than 90% were successfully produced from the proposed process with pH 5 mixed suspension at 20 °C.

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Crystal Type Iof Azilsartan Polymorphs: Preparation and Analysis

Cited by 9 publications

References 3 publications

Studies on the Crystal Forms of Istradefylline: Structure, Solubility, and Dissolution Profile

Studies on the Crystal Forms of Istradefylline: Structure, Solubility, and Dissolution Profile

Solubility of Azilsartan in Methanol, Ethanol, Acetonitrile, n-Propanol, Isopropanol, Tetrahydrofuran, and Binary Solvent Mixtures between 293.15 and 333.15 K

Crystallization of Azilsartan with Acidification of Azilsartan Disodium Salt

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