Two new nilotinib polymorphs with solubility advantages prepared by the melt crystallization process

Shi, Xiangjun; Deng, Yu; Wang, Zijuan; Chen, Qifeng; Peng, Junjie; Xing, Xiaoyi; Su, Weike

doi:10.1016/j.jddst.2023.104511

Cited by 7 publications

(12 citation statements)

References 27 publications

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“…As illustrated in Figure 1 a, the PXRD patterns of the dried samples obtained at feeding rates of 0.1 and 0.5 mL/min exhibited distinct peaks at 9.07°, 13.08°, 13.82°, 16.68°, 17.85°, 18.26°, 20.84°, 21.39°, 24.11°, and 25.22°, which corresponded to the crystalline Form A of nilotinib free base. These findings align precisely with the characteristic peaks of nilotinib free base Form A documented in the previous literature [ 25 , 26 ]. Nevertheless, when the feeding rates were set at 5, 35, and 70 mL/min, the dried samples solely exhibited the existence of a halo peak that corresponds to the amorphous state of a nilotinib free base.…”

Section: Resultssupporting

confidence: 92%

“…The DSC analysis was performed to further validate the previously mentioned findings obtained from PXRD analysis. As illustrated in Figure 2 a, the samples produced at varying feeding rates displayed a solitary endothermic peak, corresponding to the melting temperatures (T m ) of nilotinib free base crystalline Form A (T mA , 235 °C) [ 25 , 26 ]. In addition, the T mA of the samples precipitated at feeding rates of 0.1 and 0.5 mL/min was observed to be slightly lower than the T mA of the samples precipitated at feeding rates exceeding 5 mL/min.…”

Section: Resultsmentioning

confidence: 99%

“…As illustrated in Figure 5 a, the findings showed that all the samples, prepared at different agitation speeds, displayed a singular endothermic peak. This peak was associated with the melting temperature of nilotinib free base crystalline Form A (T mA , 235 °C) [ 25 , 26 ]. It was observed that all the samples exhibited an exothermic peak at 150 °C, attributed to the conversion of the amorphous solid state of nilotinib free base to crystalline Form A.…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, the samples prepared with an aging time of more than 20 min displayed two distinct endothermic peaks. The two observed peaks are attributed to the melting temperatures of crystalline Form A (T mA , 235 °C) and crystalline Form B (T mB , 245 °C) [ 25 , 26 ]. However, the peak at 245 °C was relatively small, indicating that a low quantity of crystalline Form B was formed during the heating process.…”

Section: Resultsmentioning

confidence: 99%

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Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids

Li,

Gong,

Zhang

et al. 2024

Molecules

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Amorphous solids exhibit enhanced solubility and dissolution rates relative to their crystalline counterparts. However, attaining optimal bioavailability presents a challenge, primarily due to the need to maintain the physical stability of amorphous solids. Moreover, the precise manner in which precipitation parameters, including the feeding rate of the anti-solvent, agitation speed, and aging time, influence the physical stability of amorphous solids remains incompletely understood. Consequently, this study aimed to investigate these three parameters during the precipitation process of the anticancer drug, nilotinib free base. The physical stability of the resultant samples was evaluated by employing characterization techniques including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), focused beam reflectance measurement (FBRM), and data analysis methods such as pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA). This study’s findings indicated that amorphous solids exhibited the greatest physical stability under particular conditions, namely a feeding rate of 5 mL/min, an agitation speed of 500 rpm, and an aging time of 10 min. Furthermore, the physical stability of the amorphous solids was primarily influenced by particle size and distribution, molecular interactions, microstructure, surface area, and interfacial energy. Notably, the parameters involved in the anti-solvent precipitation process, including the feeding rate of the anti-solvent, agitation speed, and aging time, exerted a significant impact on these factors. Consequently, they directly affected the physical stability of amorphous solids. Hence, this study comprehensively elucidated the mechanistic influence of these operational parameters on the physical stability of amorphous solids during the anti-solvent precipitation process.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids

Li,

Gong,

Zhang

et al. 2024

Molecules

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“…The transformation of polymorphs is a physical process of phase change and equilibrium [66,67] . From the relationship between the melting points of the two polymorphs and Tt (the intersection of two crystalline free energy curves), the stability relationship between the two polymorphs could be deduced.…”

Section: Relative Stability Between Polymorphsmentioning

confidence: 99%

Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility

Wang,

Shen,

Peng

et al. 2023

Preprint

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The development of solid-state forms of drugs is an effective mean of solubility enhancement. In this study, two polymorphs named form C, form D, and two co-crystals of sorafenib (SF) with oxalic acid (SF-OA) and malonic acid (SF-MA), by evaporation and slurry method, have been developed and characterized. The single-crystal X-ray diffraction results showed that the structure of form C was similar to of form I. It had similar cellular parameters, but different arrangement of stacking due to π-π conjugation. The drug molecules in SF-OA underwent torsional folding through four hydrogen bonds of intermolecular and intramolecular. The solubility performance of solid-state forms improved significantly. Compared with form I, form C and form D were 1.59, 1.49 times at pH 1.2 HCl, 1.59, 1.87 fold at pH 6.8 PBS. In particular, the SF-OA and SF-MA increased the apparent solubility of SF at pH 1.2 by 8.3 and 6.4 times, at pH 6.8 by 4.0 and 4.5 times respectively. The dissolution mechanisms were analyzed. New solid-state forms showed strong stability at storage conditions of 40 °C/75% RH and 60 °C/0% RH. Notably, the crystal of SF preferred to transform in mixed solvents, and the formation of co-crystals confirmed the ∆pKa rule.

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Dispersive micro-solid phase extraction based on two MOFs as highly effective adsorbents for analysis of nilotinib in plasma and wastewater

Takhvar,

Akbari,

Souri

et al. 2024

DARU J Pharm Sci

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Two new nilotinib polymorphs with solubility advantages prepared by the melt crystallization process

Cited by 7 publications

References 27 publications

Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids

Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids

Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility

Dispersive micro-solid phase extraction based on two MOFs as highly effective adsorbents for analysis of nilotinib in plasma and wastewater

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