颗粒4.0 - 高级流化床技术GydF4y2Ba
Annette Grave博士 - GLATT制药服务GydF4y2Ba
首先为化学工业开发流化床工艺，以实现比现有技术获得更好的干燥效率GydF4y2Bae。GGydF4y2Bawith tray drying. Implementation of spray nozzles in the fluid bed equipment enabled granulation processes, resulting in porous agglomerates and, processed to tablets, facilitating fast dissolution. With the development of the bottom spray technology highly efficientcoatingand layering processes became possible. While in the beginning this technology was mainly used for tablet coating, more and more processes were developed for coating of smaller particles,一世。e。GydF4y2Ba多颗粒如颗粒，miniTablets和粉末（GydF4y2Bae。G。GydF4y2BaAPI晶体）。GydF4y2Ba
多颗粒剂型由具有100-2000μm[1]的粒径的小离散单元，示出了矩阵结构（在核心中实现的API）或API分层。在颗粒或minitablets的情况下，功能GydF4y2Ba涂料GydF4y2Ba可以应用,导致味道掩盖,胃炎resistant coatings or other specific release profiles. Filling of multiparticulates into capsules or sachets and administration via sprinkling on liquids or food makes them attractive for patients who are not able to swallow monolithic dosage forms, as is the case for children or elderly. The possibility of administering different amounts of multiparticulates provides an opportunity for the development of individualized medicines. Also a compression into tablets is possible, orally disintegrating tablets (ODTs) release their discrete units in the stomach, ensuring a controlled drug release and less dependency on the gastric emptying.
Glatt offers several batch-wise or continuous technologies for the production of multiparticulates, matrix or layered pellets. Process development and optimization can be performed with quality by design approaches, process monitoring and control by state of the art PAT tools. The presentation will give an overview about the recent and most prevalent manufacturing methods.
批量流体床技术GydF4y2Ba
Wurster技术GydF4y2Ba
Wurster技术[图1]是用于药物分层的经典流化床技术和甚至非常小的多颗粒和粉末的药物分层和（功能）涂层。将分层或涂布液与流化空气同时喷射到循环流体床中。在高热转移的环境中，液体经常并在基板上反复施加为液滴[图1]，最终导致致密的涂层。GydF4y2Ba
图1GydF4y2Ba：Wurster技术，涂层工艺（GLATT制药服务GmbH＆Co.KG）GydF4y2Ba
CPSTM值GydF4y2BaTechnology
The CPSTM值GydF4y2Ba技术[图。2]允许制备两种负载的高药物以及低剂量的基质粒料，尺寸降至150μm。基于先进的流化床转子技术，CPSGydF4y2BaTM值GydF4y2Batechnology works with a conical shaped rotating disc and devices providing a directed product flow. No starting beads are required. The powder, containing API and typically microcrystalline cellulose is wetted by the pelletizing liquid until a pre-defined moisture level (and with this: particle size) is obtained. Due to centrifugal forces, spherical particles are formed and densified, characterized by smooth surfaces, narrow particle size distribution [Figure 3] and low porosity and attrition.
图2.GydF4y2Ba: CPSTM值GydF4y2Ba技术，造粒过程（Glatt Pharmaceutical GmbH＆Co.KG）GydF4y2Ba
图3.GydF4y2Ba：用CPS生产的基质颗粒GydF4y2BaTM值GydF4y2Batechnology (left), and MicroPxTM值GydF4y2Batechnology (middle, and right, Glatt Pharmaceutical Services GmbH & Co. KG)
连续流体床技术GydF4y2Ba
MicroPXTM值GydF4y2Ba/ Procell Technology
微循环GydF4y2BaTM值GydF4y2Ba技术是生产高药物负载颗粒的优选选择，API含量高达95％。可以获得150μm或更大的球形和光滑颗粒[图3]，表现出窄的粒度分布。在该连续方法中，将含有液体（溶液，悬浮液，乳液，熔体[2]）的API喷射到空的过程室中。最初，通过喷雾干燥产生细粉末，其与种子连续凝聚，并通过进一步分层，进一步分层。大小尺寸的颗粒由筛子排出;分类空气确定所得到的粒度。该方法的特征在于喷雾干燥，分层和粗大粒料排出之间的平衡比率。GydF4y2Ba
与micropx相反GydF4y2BaTM值GydF4y2Batechnology the process gas enters the process chamber in the ProCellTM值GydF4y2Ba不是通过入口空气分配板，但通过设备下部的插槽，导致喷出的床[图4]。将产物与热表面的接触最小化，因此该技术也适用于酶等热敏物质。GydF4y2Ba
图4.GydF4y2Ba：micropx.GydF4y2BaTM值GydF4y2Ba（左）和procellGydF4y2BaTM值GydF4y2Ba(right) technology, pelletization process (Glatt Pharmaceutical Services GmbH & Co. KG)
过程控制GydF4y2Ba
为实现健壮的和可再生的production processes, the critical quality attributes for a manufacturing process shall be known [3]. After a risk analysis, a design of experiments (DoE) with planned trials is applied, to define the design space and a control strategy for selected process parameters. PAT toolse。G。GydF4y2Bafor online measurement of moisture, API content and particle size distribution can be applied for automated end point detection, to reduce the offline control and release testing.
DOWNLOAD THE PRINTABLE OVERVIEW PELLET TECHNOLOGIES
REFERENCES
[1] Poellinger，N。，创新的Glatt流化床造粒技术，GydF4y2BaInternational Pharmaceutical Industry, Vol. 3, pp. 92 – 97
[2] Heinrich, S., Peglow, M., Henneberg, M., Drechsler, J., Mörl, l., Jacob, M., Pharmaceutical Process and Product Design by Fluidized Bed Spray Granulation: Modelling and Simulation Tools, Proc. International Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Nuremberg, 15 – 18 March 2004
[3] ICH指南，药物发展Q8（R2）[2009]GydF4y2Ba