Development of On-Line XRD Pharmaceutical Process Analyzer

项目描述（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、易于操作的x射线衍射仪器，用于制药行业研究、开发和生产阶段的活性药物成分（API）晶体浓度和相组成的测量，并可能扩展到其他行业。这也可以在线用于试点生产和制造环境中药品质量的初步测量。x射线光学系统（XOS）是制造先进x射线光学和光学分析仪的全球领导者，bristol - myers - squibb （BMS）是制药研究和开发的全球领导者，拥有开发成功仪器所需的专业知识。SBIR I期提案的目的是证明开发一种紧凑型分析仪的可行性，该分析仪能够在开发和生产的各个阶段在线或在线监测活性药物成分（API）。这将通过开发一种新型、低功耗、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。具体来说，粉末XRD （PXRD）装置将使用一个50 W的x射线源和一个准直的多毛管x射线光学装置，以高精度确定原料药中适当的晶体信息和多晶型。这种新技术具有无损、快速、对样品位置和粗糙度不敏感等特点。此外，系统设备将是紧凑和便携的，因此，它将很容易集成到一个联机生产系统。为了证明该技术的适用性，XOS提议探索来自制药行业的特定API，这些API一直具有挑战性，无法使用现有的PXRD技术开发生产模型。平行束XRD已被用于药物的表征（Yin 2007）。本研究已在标准实验室系统上证明了该方法的可行性。由于高功率x射线源的占地面积、功率要求和冷水冷却，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计划通过以下几个方面来开发和演示PXRD装置的性能：1)特定样品特征的区分，2)新数据与常规实验室数据的相关性，3)可重复性，以及4)设计一种新的样品处理方法。该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。这种机器的适用性包括通过更快速和成本有效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），以及通过设计改善药物质量（QbD）。

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).