Drug solid-state screening
Rapid and precise deciphering of complex formulations
In-depth analysis of solid-state properties
Development and Industrialization of Solid State
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第一行主标题 请输入要描述的内容进行内容补充请输入 - Polymorphy identification in ultra-low content formulations 第一行主标题 请输入要描述的内容进行内容补充请输入 - Non-destructive reverse engineering of advanced formulations 第一行主标题 请输入要描述的内容进行内容补充请输入 - Identification of unknown excipients |
Crystallization Process and Product Online Monitoring We provide direct support and consulting services for your crystallization processes, ensuring they are scalable, reproducible, and transferable. Additionally, we integrate Process Analytical Technology (PAT) to ensure that your crystallization products consistently achieve the desired crystal form, morphology, and size. Control of the crystallization process The relationship between formulation processes and crystal forms ■ Screening all possible solid forms of new chemical entities Combining the characteristics of the compound, employ appropriate techniques for crystal form screening such as chemical recrystallization, rapid solvent removal, and physical lattice disruption methods to explore potential polymorphs. The same polymorph may appear under different conditions, and the same conditions may yield different polymorphs, encompassing as many crystallization methods as possible. ■ Determining the most suitable solid-state form for drug development Characterize multiple crystalline samples prepared using X-ray powder diffraction, Raman spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), etc., to distinguish between different polymorphs. Study the stability and transformation patterns of polymorphs under different experimental conditions, investigating differences in dissolution properties among different polymorphs. Considering polymorph stability, solubility, particle size, flowability, etc., confirm the most suitable solid-state form for development among the new polymorphs. ■ Crystallization process development Crystallization is the process of precipitating solid substances in crystalline form from vapor, solution, or melt, which is an effective method for producing pure substances. The quality of crystalline products, including purity, crystal form, particle size, etc., is mainly determined by the crystallization process. The choice of crystallization solvent directly impacts crystal form, purity, color, etc. By systematically studying the crystallization process, examining the effects of different cooling rates, stirring speeds, and seed crystals on crystalline products, identify the optimal process conditions for advantageous polymorphs, laying a solid foundation for scaling up in industrial production designs. References：Qu H, Munk T, Cornett C, Wu J X, Bøtker JP, Christensen L P, Rantanen J, Tian F, Pharmaceutical Research 2010, 28, 364-373. Strict monitoring of the crystallization process is crucial for understanding crystallization conditions and establishing a stable crystallization system. During drug crystallization, multiple different crystal forms may emerge, and these forms may undergo transformations as the crystallization progresses. Through Raman spectroscopy, real-time monitoring of the formation process of different crystal forms can be easily achieved, providing simple and effective insights into crystallization dynamics. References：Tian F, Qu H, Louhi-Kultanen M, Rantanen J, Journal of Crystal Growth 2009, 311: 2580-2589 Production process monitoring In the figure above, it is evident that the manufacturing process of pharmaceuticals can easily lead to polymorphic transformations, especially when metastable forms of crystals are involved as the main active pharmaceutical ingredient (API). Throughout the entire preparation process of formulations, the crystalline form of the drug is susceptible to transformation due to factors such as solvents, temperature variations, humidity, pressure, grinding, and excipients. For instance, in the wet granulation process, the drug may dissolve during the addition of binders and then precipitate during drying, potentially resulting in a different crystal form than the original. It is crucial in crystallographic studies to understand that the development of drug crystal forms is inseparable from formulation design and the rational selection of administration routes. The ultimate goal of developing new crystal forms is to safely produce a stable dosage form suitable for administration. Optimal formulation design, correct excipient selection, production methods, and dissolution test monitoring constitute a comprehensive framework. Raman spectroscopy is the only instrument capable of real-time monitoring of drug crystal forms at the molecular level, applicable to every stage of the aforementioned processes. Importantly, Raman spectroscopy is one of the most promising Process Analytical Tools (PAT). In 2004, the FDA clearly outlined guidelines for the use of online monitoring instruments (PAT). PAT not only serves as a quality check for production processes but also employs systematic methods to deeply understand, design, analyze, and control production processes to achieve the desired product quality. This rigorous and systematic approach is known as Quality by Design (QbD), where PAT plays a crucial role. Traditional offline analytical tools suffer from the drawback that any crystal form changes occurring during the production process are not detected until the final product analysis, resulting in wasted time, materials, and labor. Real-time analysis during production processes provides an optimal solution to this issue. Online monitoring instruments (PAT) generate detailed and meaningful detection results in real time, which can be simultaneously fed back to process control systems to ensure consistent product quality. Raman spectroscopy, as one of the most promising PAT tools, offers the following advantages: ■ Monitoring of drug crystal changes in real time during production ■ Timely feedback with comprehensive and detailed information ■ Remote operation, automatic measurement ■ Sample measurement directly through sample vials without any sample preparation ■ Non-destructive to samples ■ Capable of measuring various sample forms: liquid, semi-solid, solid, paste, etc. ■ Simple operation and rapid measurement Utilizing Raman spectroscopy with modern multi-factor data processing allows for in-depth understanding of production processes in the pharmaceutical industry and research institutions, significantly improving drug production efficiency. It is worth noting that Raman spectroscopy can collect data directly through sealed glass containers or vials containing samples. Using remote fiber probes enables flexible online monitoring, and integration with other analytical techniques for multi-parameter measurements greatly increases the amount and accuracy of information obtained during sample production processes. This approach enables precise online monitoring and sample control during processes involving solid or semi-solid formulations, such as heating, grinding, granulation, and spray drying, which are prone to crystal form changes. Case Study: Successful Monitoring of Polymorphic Transformation Using Raman Probe during Fluid Bed Drying Using Raman spectroscopy, the main drug theophylline undergoes a polymorphic transformation process from its monohydrate to anhydrate form during fluid bed drying, which can be monitored continuously throughout the process. This process clearly demonstrates the crystalline stability of the main drug, potential polymorphic transformations during drying, and the parameters necessary for the drying process. References：Aaltonen et al. Chem. Eng. Sci. 62 (2007) 408-415. Possible production processes and factors that may cause solid-state changes in pharmaceuticals: |
Solid State Research
Improving drug absorption through solid-state technology is the foundation of all innovative technologies at Xinyang Weikang.
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Innovative Improved Drugs
Our company strategically focuses on developing high-end formulations, successfully completing numerous advanced oral film formulations, and establishing a systematic approach to formulation development.
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CDMO
We are the only integrated domestic platform specializing in crystalline formulation production, strictly adhering to GMP standards. We specialize in scaling up research and commercial production of various dosage forms including oral films, topical formulations, and solid formulations.
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Nycrist Phamatech Co.,Ltd
Tel：19129598229
19129598368（Mr.Lee）
19926561149（Mrs.Chen）
19926414326（Mr.Liu）
Headquarters Address: Building A3, Guanming Technology Park, No. 3009 Guangming Avenue, Fenghuang Community, Fenghuang Street, Guangming District, Shenzhen
Production Base Address: Weiguang Life Science Park, Guangming District, Shenzhen
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