Vercruysse J, Peeters E, Fonteyne M, Cappuyns P, Delaet U, Van Assche I, De Beer T, Remon J P, Vervaet C
Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
Eur J Pharm Biopharm. 2015 Jan;89:239-47. doi: 10.1016/j.ejpb.2014.12.017. Epub 2014 Dec 17.
Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and tablet quality attributes were obtained during the start-up phase of the 1h run. For the single cell runs, granule and tablet properties were comparable with results obtained during the second part of the 1h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for tablet quality obtained during continuous production using the ConsiGma™-25 system.
由于小规模生产是在制药行业成功引入连续技术以使其能在配方开发和工艺优化过程中使用的关键，因此必须确定与大量物料的连续加工相比，少量物料加工时产品质量是否相似。所以，本研究的目的是调查在ConsiGma™-25系统（由GEA Pharma Systems公司推出的一种连续双螺杆制粒和干燥系统，型号为Collette™，位于比利时沃梅尔海姆）的六段式流化床干燥机的单个单元中加工的物料，在全规模生产且所有干燥单元都装满物料时，是否能预测颗粒和片剂的质量。此外，还对ConsiGma™-1系统（一个移动实验室单元）的性能进行了评估，并与ConsiGma™-25系统进行了比较。将两种活性成分、微晶纤维素、玉米淀粉、预胶化淀粉和淀粉乙醇酸钠的预混物用蒸馏水制粒。干燥和研磨（1000μm，800转/分钟）后，将颗粒与硬脂酸镁混合，并使用Modul™ P压片机进行压片（片剂重量：430mg，主压力：12kN）。使用ConsiGma™-25系统和ConsiGma™-1系统进行的单细胞实验重复进行了三次。此外，使用ConsiGma™-25系统进行了1小时的连续运行。评估了工艺结果（扭矩、料筒壁温度、干燥过程中的产品温度）以及颗粒（残留水分含量、粒度分布、堆密度和振实密度、豪斯纳比、脆碎度）和片剂（硬度、脆碎度、崩解时间和溶出度）的质量属性。通过进行1小时的连续运行，发现由于物料在螺杆和螺杆腔壁上的初始分层，扭矩和料筒壁温度需要一个稳定期。因此，在1小时运行的启动阶段获得的颗粒和片剂质量属性略有偏差。对于单细胞运行，颗粒和片剂性质与1小时运行第二部分（启动后）获得的结果相当。尽管由于本研究中使用的ConsiGma™-1单元和ConsiGma™-25系统（水平设置）的不同设计，观察到颗粒质量存在偏差（粒度分布和豪斯纳比），但使用ConsiGma™-1系统加工的颗粒生产的片剂质量能够预测使用ConsiGma™-25系统连续生产时获得的片剂质量。
