Aleksandr B. Stefaniak , Lauren N. Bowers , Elizabeth D. Brusak , Robert P. Streicher , Alvaro Goyanes , Sherri A. Friend , Duane R. Hammond , Ryan F. LeBouf , Chaolong Qi , M.Abbas Virji
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引用次数: 0
摘要
3D打印技术有望彻底改变制药行业,因此为了广泛的临床应用,评估其安全性并最大限度地发挥其效益势在必行。在此,首次在测试室中监测模型药物(荧光素)打印过程中的颗粒排放以评估释放。采用热熔挤压(HME)或扩散(被动加载)技术制备荧光素,利用长丝挤压型3D打印机制备片剂。对打印机的表面污染进行了定性记录。印刷过程中释放到空气中的荧光素平均浓度低于HME的分析检测限,扩散限为0.92 ± 0.20 ng/m3。使用HME长丝(5.01 x 104)打印时,空气动力学粒度仪数据(#/g挤压)的颗粒产量显著降低(p 6)。数学模型被用来预测如果工人吸入颗粒可能在呼吸系统中沉积的位置。预测显示,与HME相比,弥散负荷细丝在头部和肺(肺泡)区域沉积的颗粒比例更大,尽管不显著。荧光素转移到个人防护设备(手套)和打印机表面,这表明皮肤接触和交叉污染的可能性。假设我们的结果代表了活性药物成分,它们支持控制的重要性,例如密封以尽量减少吸入暴露和清洁以尽量减少皮肤暴露和片剂交叉污染。
Influence of filament loading technique on surrogate active pharmaceutical ingredient particle emissions during material extrusion 3D printing of tablets
3D printing holds great promise to revolutionize pharmaceutical manufacturing, so for widespread clinical application, it is imperative to evaluate its safety and maximize its benefits. Herein, for the first time, particle emissions of the printing process of a model drug (fluorescein) were monitored in a test chamber to evaluate release. A filament extrusion-type 3D printer was used to make tablets from filaments loaded with fluorescein prepared by hot melt extrusion (HME) or diffusion (passive loading) techniques. Surface contamination of the printer was qualitatively documented. Average concentrations of fluorescein released into air during printing were below the analytical limit of detection for HME and 0.92 ± 0.20 ng/m3 for diffusion. Particle yield from the aerodynamic particle sizer data (#/g extruded) during printing with HME filament (5.01 x 104) was significantly lower (p < 0.05) compared with diffusion filament (1.07 x 106). Mathematical modeling was used to predict where particles might deposit in the respiratory system if inhaled by a worker. Predictions showed larger fractions of particles deposited in the head and pulmonary (alveolar) regions from diffusion-loaded filament compared with HME, albeit non-significant. Fluorescein was transferred onto personal protective equipment (gloves) and printer surfaces, which indicated potential for dermal exposure and cross-contamination. Assuming our results are representative of active pharmaceutical ingredients, they support the importance of controls such as containment to minimize inhalation exposure and housekeeping to minimize dermal exposure and cross-contamination of tablets.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.