从无形固体再结晶的加速稳定性建模分散:一个Griseofulvin/HPMC-AS案例研究
Ariana Sheng-Chu Leon1, Kenneth C Waterman2, Guanhua Wang1
1Level 2, Block C3, Maple Science Park, Qixia District, Nanjing 210048 China.
International journal of pharmaceutics
|May 3, 2024
概括
预测无形固体分散 (ASD) 中的再结晶对于药物稳定性至关重要. 本研究使用加速稳定性评估程序 (ASAP) 准确建模保质期并防止药物结晶.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
背景情况:
- 无形固体分散 (ASDs) 增强了水溶性较差的药物的口服生物可用性.
- 在储存过程中预测ASD结晶是至关重要的,但由于量化限制和复杂的动力学,这是具有挑战性的.
- 目前用于预测ASD稳定的方法耗时且准确性有限.
研究的目的:
- 使用加速稳定性评估程序 (ASAP) 开发和验证无形固体分散 (ASD) 的预测性保质期模型.
- 通过使用先进的动力建模技术,提高预测ASD结晶水平的准确性.
- 建立一种可靠的方法来评估ASD在各种压力条件下的长期稳定性.
主要方法:
- 使用喷雾干燥 (灰色富尔文和HPMC-AS-LF) 制备一个模拟无形固体分散 (ASD) 模型.
- 应用加速稳定性评估程序 (ASAP) 以异构转换和修改的阿雷尼乌斯方法在玻璃过渡温度 (Tg) 以下.
- 开发和利用一种敏感的X射线粉末衍射 (XRPD) 方法来量化压力ASD样本中的晶体含量.
主要成果:
- ASAPprime®模型显示,与长期的 (40°C/75%RH) 结晶度水平有很好的一致性.
- 开发的XRPD方法提供了压力ASD中的晶体含量的敏感量化.
- 加速稳定性研究表明,有可能提高ASD保质期预测的准确性.
结论:
- 加快稳定性评估程序 (ASAP) 有效地预测无形固体分散 (ASD) 中的结晶.
- 这种方法提高了对ASD的保质期预测的准确性,这对于药物产品开发至关重要.
- 该研究支持使用ASAP进行无形固体分散物的可靠和有效的稳定性评估.
相关概念视频
Recrystallization: Solid–Solution Equilibria
1.1K
Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...
1.1K
Precipitation Processes
446
The experimental conditions in a gravimetric analysis should be optimized to maximize the particle size and purity of the obtained precipitate. Ideally, the concentration of the precipitating reagent should be low with effective stirring to maintain low relative supersaturation for the growth of large crystals. In homogeneous precipitation, the precipitant is slowly generated by a chemical reaction in the solution to avoid local reagent excesses. For example, urea decomposes gradually to...
446
Crystal Growth: Principles of Crystallization
1.9K
Crystallization is a phase transformation process in which crystals are precipitated from a supersaturated solution or formed from other sources. During crystallization, atoms or molecules arrange themselves into a well-defined, rigid crystal lattice to minimize energy.
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent...
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent...
1.9K
Polymer Classification: Crystallinity
2.8K
Unlike ionic or small covalent molecules, polymers do not form crystalline solids due to the diffusion limitations of their long-chain structures. However, polymers contain microscopic crystalline domains separated by amorphous domains.
Crystalline domains are the regions where polymer chains are aligned in an orderly manner and held together in proximity by intermolecular forces. For example, chains in the crystalline domains of polyethylene and nylon are bound together by van der Waals...
Crystalline domains are the regions where polymer chains are aligned in an orderly manner and held together in proximity by intermolecular forces. For example, chains in the crystalline domains of polyethylene and nylon are bound together by van der Waals...
2.8K
Colloidal precipitates
574
The high insolubility of some precipitates can result in an unfavorable relative supersaturation. This can lead to colloidal particles with a large surface-to-mass ratio, where adsorption is promoted. For instance, in the precipitation of silver chloride, silver ions are adsorbed on the surface of the colloidal particles, forming a primary layer. This layer attracts ions of opposite charge (such as nitrate ions), forming a diffuse secondary layer of adsorbed ions. This electric double layer...
574


