Development of On-Line XRD Pharmaceutical Process Analyzer

描述(申请人提供)：该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)的晶体浓度和物相组成，并可能推广到其他行业。这也可用于在中试生产和制造环境中对药物质量进行初步在线测量。X射线光学系统公司(XOS)和百时美施贵宝公司(BMS)组成的团队拥有研发成功仪器所需的专业知识。XOS公司是制造先进的X射线光学和光学分析仪的世界领先企业，百时美施贵宝(BMS)是制药领域的全球领先企业。SBIR第一阶段提案的目的是证明开发一种紧凑型分析仪的可行性，该分析仪能够在线或在线监测开发和生产的不同阶段的活性药物成分(API)。这将通过开发一种新型的、低功率、完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。具体地说，粉末X射线衍射仪(PXRD)将使用50W X射线源与准直多毛细管X射线光学系统相结合，以高精度确定原料药中适当的结晶信息和多晶型。这项新技术将是非破坏性的，快速的，对样品位置和粗糙度不敏感。此外，系统设备将紧凑和便携，因此，它将很容易集成到在线生产系统中。为了证明这项技术的适用性，XOS建议探索制药行业的特定原料药，这些原料药在使用现有的PXRD技术开发生产模型方面一直具有挑战性。平行束X射线衍射法已被用于药物的表征(尹某，2007)。这项研究已经论证了建立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，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建议通过以下几个方面开发和展示PXRD设置的性能：1)区分特定的样品特性，2)新数据与常规实验室数据的相关性，3)重复性，以及4)设计新的样品处理方法。拟议的分析器将通过提高药物开发效率和缩短制造工艺的周转时间对公众产生积极影响。这种机器的适用性包括通过更快速和更具成本效益的仪器促进提高药物研究的吞吐量，使用主要测量方法实施药物过程分析技术(PAT)，以及通过设计(QBD)改进药物质量。

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).