Development of On-Line XRD Pharmaceutical Process Analyzer

在线XRD制药过程分析仪的研制

• 批准号: 7478708
• 负责人: Huapeng Huang
• 金额: $ 9.93万
• 依托单位: X-RAY OPTICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-22 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478708
• 关键词: Address; Characteristics; Chills; Complex; Computer software; Concentration measurement; Coupled; Crystallization; Data; Development; Drug Industry; Ensure; Environment; Equipment; Evaluation; Feasibility Studies; Feedback; General Population; Government; In Situ; Industry; Laboratories; Measurement; Measures; Methods; Modeling; Monitor; Numbers; Optics; Performance; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Positioning Attribute; Powder dose form; Preparation; Process; Production; Prohibit; Purpose; Range; Reaction; Reproducibility; Research; Resolution; Resources; Roentgen Rays; Safety; Sampling; Scanning; Series; Shapes; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Solutions; Source; Speed; Staging; Standards of Weights and Measures; Synchrotrons; System; Techniques; Technology; Temperature; Time; United States Food and Drug Administration; Variant; Water; Work; X ray diffraction analysis; X-Ray Diffraction; Yin; analytical tool; base; concept; cost; cost effective; design; detector; drug development; drug production; drug quality; improved; innovation; instrument; manufacturing process; neutrophil; novel; pill; prototype; research and development; research study; scale up; size; success; time use; tool

DESCRIPTION (provided by applicant): This project involves development of a low-power, compact and portable, reliable, safe, and easy-to- operate x-ray diffraction instrument for measurement of crystal concentration and phase composition for active pharmaceutical ingredients (API) in the stages of research, development, and production for the pharmaceutical industry and possibly extended to other industries. This could also be used online for primary measurement of drug quality in pilot production and manufacturing environments. The team of X-ray Optical Systems (XOS), a world leader in manufacturing advanced x-ray optics and optics enabled analyzers, and Bristol-Meyers-Squibb (BMS), a world leader in pharmaceutical research and development, has the expertise necessary to develop a successful instrument. The objective of this SBIR Phase I proposal is to demonstrate the feasibility of developing a compact analyzer capable of monitoring active pharmaceutical ingredients (API) online or at-line in the various stages of development and production. This will be accomplished by developing a novel, low-power, fully enclosed and shielded, parallel-beam x-ray diffraction (XRD) system to apply new analysis techniques. Specifically the powder XRD (PXRD) setup would use a 50 W x-ray Source coupled with a collimating polycapillary x-ray optic to determine the proper crystalline information and polymorphs in the API with a high degree of accuracy. This new technique will be non-destructive, rapid, and insensitive to sample position and roughness. In addition, the system equipment will be compact and portable, therefore, it will be easily integrated in an on-line production system. In order to demonstrate the applicability of this technique, XOS proposes to explore specific API's from the pharmaceutical industry that have been challenging to develop production models for, using existing PXRD technology. Parallel beam XRD has been used for characterization of pharmaceuticals (Yin 2007). This study has already demonstrated the feasibility on a standard laboratory system. Due to the extended footprint, power requirements and chilled-water cooling for high power x-ray source, the system is not suitable for a typical production environment. XOS can leverage the new source-optic coupled technologies to demonstrate the low- power, compact, easy-to-use, measurement method. In Phase I, XOS proposes to develop and demonstrate the performance of the PXRD setup via: 1) differentiation of particular sample characteristics, 2) correlation of new data with conventional laboratory data, 3) reproducibility, and 4) design a novel sample handling method. The proposed analyzer will have a positive impact to the general public by increasing drug development efficiency and shortening the turnaround times for manufacturing processes. The applicability for such a machine includes facilitating improved throughput of drug research with a more rapid and cost effective instrument, implementation of drug process analytical technology (PAT) using a primary measurement method, and improvements in drug quality by design (QbD).

描述（由申请人提供）：本项目涉及开发一种低功耗、紧凑便携、可靠、安全和易于操作的X射线衍射仪，用于在制药行业的研究、开发和生产阶段测量活性药物成分（API）的晶体浓度和相组成，并可能扩展到其他行业。这也可以在线用于在试点生产和制造环境中对药物质量进行初步测量。X射线光学系统（XOS）是制造先进X射线光学器件和光学启用分析仪的世界领导者，Bristol-Meyers-Squibb（BMS）是制药研究和开发的世界领导者，拥有开发成功仪器所需的专业知识。本SBIR I期提案的目的是证明开发一种能够在开发和生产的各个阶段在线或在线监测活性药物成分（API）的紧凑型分析仪的可行性。这将通过开发一种新型、低功率、全封闭和屏蔽的平行光束X射线衍射（XRD）系统来实现，以应用新的分析技术。具体地，粉末XRD（PXRD）装置将使用与准直多毛细管X射线光学器件耦合的50 W X射线源，以高精度确定API中的适当结晶信息和多晶型物。这种新技术将是非破坏性的，快速的，样品的位置和粗糙度不敏感。此外，系统设备将是紧凑和便携式的，因此，它将很容易集成到一个在线生产系统。为了证明该技术的适用性，XOS建议使用现有的PXRD技术探索制药行业的特定API，这些API一直难以开发生产模型。平行光束XRD已用于表征药物（Yin 2007）。这项研究已经证明了标准实验室系统的可行性。由于高功率X射线源的占地面积、功率要求和冷冻水冷却的扩展，该系统不适合典型的生产环境。XOS可以利用新的源光耦合技术来展示低功耗、紧凑、易于使用的测量方法。在第一阶段，XOS建议通过以下方式开发和展示PXRD装置的性能：1）区分特定的样品特性，2）将新数据与传统的实验室数据相关联，3）再现性，以及4）设计一种新的样品处理方法。拟议的分析仪将通过提高药物开发效率和缩短制造过程的周转时间对公众产生积极影响。这样的机器的适用性包括促进提高药物研究的吞吐量与更快速和成本效益的仪器，使用主要测量方法的药物过程分析技术（PAT）的实施，并通过设计（QbD）提高药物质量。