Selective Acceleration of Crystal Growth of Indomethacin Polymorphs by Low-Concentration Poly(ethylene oxide),Molecular Pharmaceutics

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Selective Acceleration of Crystal Growth of Indomethacin Polymorphs by Low-Concentration Poly(ethylene oxide)
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-11-21 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00854
Qin Shi ₁ , Jie Zhang ₁ , Chen Zhang ₂ , Jing Jiang ₂ , Jun Tao ₁ , Dongshan Zhou ₂ , Ting Cai _{1,

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Affiliation

Physical stability of pharmaceutical amorphous solid dispersions is one of the critical attributes to the successful development of the formulation. Herein, we studied the impact of low-concentration poly(ethylene oxide) (PEO) on the crystallization rates of three polymorphs of indomethacin (IMC, γ-, α-, and δ-form). We observed that the addition of 3% w/w PEO significantly increased the crystal growth rates of γ-form and α-form of IMC, but had a negligible effect on the δ-form. The reduction of the activation energy for the crystal growth of IMC polymorphs after adding the PEO follows the order γ-form > α-form > δ-form, which is consistent with the trend toward the accelerating effects of PEO on the crystal growth rates of three polymorphs. With the addition of low-concentration PEO, there is an increase of molecular mobility of IMC as evidenced by the decreased structural relaxation times and viscosities. This study suggests that the substantially different effects of PEO on the crystal growth rates of IMC polymorphs are attributable to the different adsorption of PEO on the crystal surface of those polymorphs, which in turn exerts a selective accelerating effect on IMC molecules to organize into the different crystalline phases. These findings are relevant for understanding the crystallization behavior of amorphous solid dispersions containing polymorphic drugs.

中文翻译：

低浓度聚环氧乙烷对吲哚美辛多晶型物晶体生长的选择性加速

药物无定形固体分散体的物理稳定性是制剂成功开发的关键属性之一。在这里，我们研究了低浓度聚环氧乙烷（PEO）对消炎痛三种多晶型物（IMC，γ-，α-和δ-形式）结晶速率的影响。我们观察到3％w / w PEO的添加显着提高了IMC的γ型和α型晶体的生长速率，但对δ型的影响可忽略不计。加入PEO后，IMC多晶型物晶体生长的活化能降低遵循γ-型>α-型>δ-型的顺序，这与PEO促进PSO晶体生长速率的趋势一致。三个多态。加上低浓度的PEO，降低的结构弛豫时间和粘度证明了IMC分子迁移率的增加。这项研究表明，PEO对IMC多晶型物晶体生长速率的影响本质上不同，这归因于PEO在这些多晶型物晶体表面上的不同吸附，进而对IMC分子产生了选择性促进作用，从而组织成不同的结晶相。这些发现与理解含多晶型药物的无定形固体分散体的结晶行为有关。这项研究表明，PEO对IMC多晶型物晶体生长速率的影响本质上不同，这是由于PEO在这些多晶型物晶体表面上的吸附不同，从而又对IMC分子产生了选择性促进作用，从而组织成不同的结晶相。这些发现与理解含多晶型药物的无定形固体分散体的结晶行为有关。这项研究表明，PEO对IMC多晶型物晶体生长速率的影响本质上不同，这是由于PEO在这些多晶型物晶体表面上的吸附不同，从而又对IMC分子产生了选择性促进作用，从而组织成不同的结晶相。这些发现与理解含多晶型药物的无定形固体分散体的结晶行为有关。

更新日期：2017-11-22

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