Zheng Zijie, Lv Jieqiong, Yang Wei, Pi Xueying, Lin Wei, Lin Zhanyi, Zhang Wenfang, Pang Jiali, Zeng Yingtong, Lv Zhufen, Lao Haiyan, Chen Yanzhong, Yang Fan
The Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.
Guangdong Provincial People's Hospital, Guangzhou, 510080, Guangdong, China.
Eur J Pharm Sci. 2020 Mar 4;149:105293. doi: 10.1016/j.ejps.2020.105293.
This study aimed to use three-dimensional printing technology to provide patients with accurate, safe and convenient subdivided drugs and bring the transformation of subdivided drugs' fabrication in the hospital. The formulation, preparation process, model and printing parameters, relationship between dose and preset model for printing of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg subdivided tablets prepared by three-dimensional printers were investigated in the study. The three-dimensional printed material consists of commercial tablets powders and other excipients, including lactose, corn starch, microcrystalline cellulose, and so on. Mass variation, drug content and drug content uniformity of subdivided tablets obtained by three-dimensional printing were compared with the pharmacists splitting subdivided tablets. Besides, the results from fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction confirmed that the preparation process of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg did not change the crystal structure of the active pharmaceutical ingredient. Furthermore, mass variation, drug content range and drug content uniformity of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg tablets split by pharmacists failed to comply with European Pharmacopoeia and Chinese Pharmacopoeia, while those of the three-dimensional printed subdivided tablets did. After the review of the ethics committee as a new technology for hospital dispensing, three-dimensional printed spironolactone subdivided tablets of 2 mg have been used in clinical inpatients and was accepted by pharmacists, nurses and patients. Compared with tablets subdivided split by pharmacists, three-dimensional printed spironolactone tablets of 2 mg were more accurate, safer and more customized, which indicated considerable potential in using three-dimensional printing technology as a new method for hospital dispensing.
本研究旨在利用三维打印技术为患者提供准确、安全且便捷的细分药物，并推动医院细分药物制备方式的变革。本研究对三维打印机制备的2毫克螺内酯、4毫克螺内酯及5毫克氢氯噻嗪细分片剂的处方、制备工艺、模型及打印参数、打印剂量与预设模型之间的关系进行了研究。三维打印材料由市售片剂粉末及其他辅料组成，包括乳糖、玉米淀粉、微晶纤维素等。将三维打印得到的细分片剂的质量差异、药物含量及药物含量均匀度与药剂师手工分割的细分片剂进行比较。此外，傅里叶变换红外光谱、差示扫描量热法及X射线粉末衍射结果证实，2毫克螺内酯、4毫克螺内酯及5毫克氢氯噻嗪的制备过程未改变活性药物成分的晶体结构。再者，药剂师手工分割的2毫克螺内酯、4毫克螺内酯及5毫克氢氯噻嗪片剂的质量差异、药物含量范围及药物含量均匀度不符合欧洲药典和中国药典要求，而三维打印细分片剂的则符合要求。作为医院配药的一项新技术，经伦理委员会审查后，2毫克三维打印螺内酯细分片剂已应用于临床住院患者，并得到了药剂师、护士及患者的认可。与药剂师手工分割的片剂相比，2毫克三维打印螺内酯片剂更准确、更安全且更具个性化，这表明三维打印技术作为医院配药新方法具有巨大潜力。
