Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX 77843, USA.
Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX 77843, USA; Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Int J Pharm. 2019 Oct 30;570:118651. doi: 10.1016/j.ijpharm.2019.118651. Epub 2019 Sep 4.
The focus of the study was to understand the effects of formulation and process variables on the printlets quality manufactured by selective laser sintering (SLS) 3D printing. The Box-Behnken response surface methodology was used to evaluate effects of individual variables and combinations thereof. The formulation and process variables studied were printing chamber temperature (°C, X), laser scanning speed (mm/sec, X) and lactose monohydrate concentration (%, X). The responses studied were weight of printlets (mg, Y), hardness (N, Y), disintegration time (sec, Y) and dissolved drug fraction in 15 min (%, Y). The values of Y, Y, Y and Y varied from 170.2-257.0 mg, 5.5-32.0 N, 20-120 s and 64.4-97.5%, respectively. The studied factors showed statistically significant effects on the dependent variables (p < 0.04). The correlation coefficient between empirical and model predicted values for Y, Y, Y and Y were 0.999, 0.992, 0.998 and 0.983, respectively. The model was validated by an independent experiment and actual values of the responses were in close agreement with model predicted values. Fourier transformed infrared spectroscopy indicated no chemical interactions between the components of the formulation during printing process. X-ray powder diffractograms suggested a decrease in crystallinity of the drug and lactose in the printlets. Chemical images indicated uniform distribution of the drug. Scanning electron microscopy and X-ray micro-CT scanning showed a very porous microstructure of the printlets with a porosity of about 37.89%. In conclusion, the SLS method of manufacturing provides a feasible and flexible avenue for fabricating dosage forms with tailored characteristics.
本研究的重点是了解配方和工艺变量对选择性激光烧结（SLS）3D 打印制造的打印片质量的影响。采用 Box-Behnken 响应面法评估单个变量及其组合的影响。研究的配方和工艺变量为打印腔温度（°C，X）、激光扫描速度（mm/sec，X）和一水乳糖浓度（%，X）。研究的响应为打印片的重量（mg，Y）、硬度（N，Y）、崩解时间（s，Y）和 15 分钟内溶解药物的分数（%，Y）。Y、Y、Y 和 Y 的值分别为 170.2-257.0mg、5.5-32.0N、20-120s 和 64.4-97.5%。研究因素对各响应变量（p<0.04）有统计学显著影响。Y、Y、Y 和 Y 的实验值与模型预测值之间的相关系数分别为 0.999、0.992、0.998 和 0.983。通过独立实验验证了模型的有效性，响应的实际值与模型预测值非常吻合。傅里叶变换红外光谱表明，在打印过程中配方成分之间没有发生化学相互作用。X 射线粉末衍射图表明，药物和乳糖在打印片中的结晶度降低。化学图像表明药物分布均匀。扫描电子显微镜和 X 射线微计算机断层扫描显示，打印片具有约 37.89%的多孔微观结构，非常多孔。总之，SLS 制造方法为制造具有定制特性的剂型提供了一种可行且灵活的途径。
