过程分析技术在异醇-理论分析中获得了变态稳定区宽度,核化速率和青的溶解度
Mahmoud Ranjbar1, Mayank Vashishtha1, Gavin Walker1
1Synthesis and Solid-State Pharmaceutical Centre, Department of Chemical Sciences, Bernal Research Institute, University of Limerick, V94 T9PX Limerick, Ireland.
Pharmaceuticals (Basel, Switzerland)
|March 27, 2025
概括
本研究介绍了使用过程分析技术 (PAT) 测量转移稳定区宽度 (MSZW) 和活性药物成分 (API) 溶解度的高效方法. 这些基于PAT的协议改善了结晶过程的开发和设计质量.
科学领域:
- 制药科学 制药科学
- 化学工程是化学工程的重要组成部分.
- 结晶技术 结晶技术 结晶技术
背景情况:
- 转移稳定区宽度 (MSZW) 和溶解性对于通过结晶的活性药物成分 (API) 净化至关重要.
- 确定这些属性的传统方法耗时,需要更高效的方法.
- 过程分析技术 (PAT) 和设计质量 (QbD) 推动了对先进结晶协议的需求.
研究的目的:
- 建立用于测量溶解度和MSZW的协议,使用现场里埃变换红外光谱 (FTIR) 和聚焦束反射度测量 (FBRM).
- 用理论模型评估实验数据,包括基于古典核化理论的新型模型.
- 确定核化动力学和热力学参数,以优化结晶过程.
主要方法:
- 使用FTIR光谱和FBRM进行MSZW和溶解度的实验性确定.
- 分析红外光谱的可溶性度和FBRM计数的MSZW和超溶性.
- 将实验MSZW数据与四个理论模型相匹配,以提取核和热力学参数.
主要成果:
- 一个新的理论模型证明了与各种冷却速率的实验MSZW数据的良好一致.
- 核化速率常数和速率被确定为1021和1022分子/m3·s之间.
- 计算了关键的热力学参数,包括核的吉布斯自由能量 (3.6kJ/mol) 和表面能量 (2.68.8mJ/m2).
结论:
- 已开发的基于PAT的协议,用于预测MSZW和可溶性,可指导其他API结晶.
- 这种新的理论模型提高了核化动力学和热力学预测的准确性.
- 通过更好地理解和预测这些关键参数,可以实现优化结晶过程.
相关概念视频
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
162
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
162
Solvating Effects
7.2K
An understanding of the solvating effect helps rationalize the relation between solvation and acidity of the compound. In addition, this also explains the relative stability of conjugate bases for compounds with different pKa values. This lesson details, in-depth, the principle of solvating effects. The strength of an acid and the stability of its corresponding conjugate base are determined using pKa values. This observed relationship is a consequence of solvation, which is the interaction...
7.2K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
890
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
890
Theories of Dissolution: Diffusion Layer Model
653
Dissolution, the process by which drug particles dissolve in a solvent, is explained by the diffusion layer model, a theoretical framework that simulates the absorption of oral drugs and allows us to analyze experimental data.
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
653
Factors Influencing Drug Absorption: Drug Dissolution
393
The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
393
Noncompartmental Analysis: Mean Transit, Absorption and Dissolution Time
46
When drugs are administered extravascularly, a comprehensive evaluation through noncompartmental analysis becomes imperative. This analytical approach considers various parameters that play a crucial role in understanding the pharmacokinetics of these drugs.
One of the key parameters is the mean transit time (MTT), which refers to the total duration required for drug molecules to transit through the body. MTT is determined by calculating the ratio of the area under the moment curve to the area...
One of the key parameters is the mean transit time (MTT), which refers to the total duration required for drug molecules to transit through the body. MTT is determined by calculating the ratio of the area under the moment curve to the area...
46


