Reynolds Medical Sciences Building, Irma Lerma Rangel School of Pharmacy, Texas A&M Health Science Center, Texas A&M University, Suite 159, College Station, Texas, 77843-1114, USA.
Department of Engineering Technology & Industrial Distribution, College of Engineering, Texas A&M University, College Station, Texas, 77843, USA.
AAPS PharmSciTech. 2023 Aug 11;24(6):171. doi: 10.1208/s12249-023-02623-7.
The aim of this work was to design pediatric-friendly, dose-flexible orally disintegrating drug delivery systems (printlets) of the antiviral drug tenofovir disoproxil fumarate (TDF) by selective laser sintering (SLS) for potential use in hospitals along with other antiviral drugs. In order to obtain a consistent quality of printlets with desired properties, it is important to understand certain critical quality attributes for their main and interactions effect. The printlets were optimized by Box-Behnken's design of the experiment by varying process variables while keeping the composition constant. The composition contained 16.3% TDF, 72.7% polyvinyl pyrrolidone K16-18, 8% magnesium aluminum silicate, 3% Candurin NXT Ruby Red, and 0.3% colloidal silicon dioxide. The process variables studied were surface (X), chamber temperatures (X), and laser scanning speed (X). The range of variable levels was 75-85°C for X, 50-70°C for X, and 200-240 mm/s for X, respectively. The responses studied were hardness, disintegration time, dissolution, physiochemical, and pharmacokinetic characterization. X-ray powder diffraction indicated partial or complete conversion of the crystalline drug into amorphous form in the printlets. Comparative pharmacokinetics between Viread (generic) and printlets in rats were superimposable. Pharmacokinetic parameters showed statistically insignificant differences between the two formulations in terms of T, C, and AUC of (p > 0.05). Printlets were bioequivalent to Viread as per FDA bioequivalence criteria. Thus, the SLS printing method showed the fabrication of dose-flexible printlets with quality, and in vivo performance equivalent to commercial tablets.
这项工作的目的是通过选择性激光烧结（SLS）设计适合儿科使用的、剂量灵活的口服崩解药物输送系统（打印片），用于医院的抗病毒药物，包括其他抗病毒药物。为了获得具有所需特性的打印片的一致质量，了解其主要和相互作用的某些关键质量属性非常重要。通过 Box-Behnken 设计实验的方法，在保持成分不变的情况下，通过改变工艺变量来优化打印片。配方包含 16.3%的替诺福韦二异丙醇富马酸盐、72.7%的聚乙烯吡咯烷酮 K16-18、8%的硅酸镁铝、3%的 Candurin NXT Ruby Red 和 0.3%的胶体二氧化硅。研究的工艺变量是表面（X）、腔室温度（X）和激光扫描速度（X）。变量水平的范围分别为 X 为 75-85°C、X 为 50-70°C、X 为 200-240mm/s。研究的响应是硬度、崩解时间、溶解、物理化学和药代动力学特性。X 射线粉末衍射表明，药物在打印片中部分或完全从晶态转化为无定形态。在大鼠中，Viread（仿制药）和打印片之间的比较药代动力学是可叠加的。药代动力学参数表明，两种制剂在 T、C 和 AUC 方面的差异无统计学意义（p>0.05）。根据 FDA 生物等效性标准，打印片与 Viread 具有生物等效性。因此，SLS 打印方法显示了可制造剂量灵活的打印片，其质量和体内性能与商业片剂相当。
