Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, Reynolds Medical Sciences Building, Suite 159, College Station, Texas 77843-1114, United States.
Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Mol Pharm. 2022 Aug 1;19(8):2937-2949. doi: 10.1021/acs.molpharmaceut.2c00306. Epub 2022 Jun 1.
The focus of this research was to understand the effects of formulation and processing variables on the very-rapidly dissolving printlets of isoniazid (INH) manufactured by the selective laser sintering (SLS) three-dimensional (3D) printing method, and to characterize their physicochemical properties, stability, and pharmacokinetics. Fifteen printlet formulations were manufactured by varying the laser scanning speed (400-500 mm/s, ), surface temperature (100-110 °C, ), and croscarmellose sodium (CCS, %, ), and the responses measured were weight (), hardness (), disintegration time (DT, ), and dissolution (). Laser scanning was the most important processing factor affecting the responses. DT was very rapid (≥3 s), and dissolution (>99%) was completed within 3 min. The root-mean-square error in the studied responses was low and analysis of variance (ANOVA) was statistically significant ( < 0.05). X-ray micro-computed tomography (micro-CT) images showed very porous structures with 24.6-34.4% porosity. X-ray powder diffraction and differential scanning calorimetry data indicated partial conversion of the crystalline drug into an amorphous form. The printlets were stable at 40 °C/75% RH with no significant changes in assay and dissolution. Pharmacokinetic profiles of the printlets and compressed tablets were superimposable. In conclusion, the rapidly dissolving printlets of the INH were stable, and oral bioavailability was similar to that of compositionally identical compressed tablets.
本研究的重点是了解制剂和加工变量对通过选择性激光烧结（SLS）三维（3D）打印方法制造的异烟肼（INH）速溶打印片的影响，并对其理化性质、稳定性和药代动力学进行表征。通过改变激光扫描速度（400-500mm/s）、表面温度（100-110°C）和交联羧甲纤维素钠（CCS，%），制备了 15 种打印片制剂，测量的响应为重量（）、硬度（）、崩解时间（DT，）和溶解（）。激光扫描是影响响应的最重要的加工因素。DT 非常快（≥3s），溶解（>99%）在 3 分钟内完成。研究响应的均方根误差较低，方差分析（ANOVA）具有统计学意义（<0.05）。X 射线微计算机断层扫描（micro-CT）图像显示具有 24.6-34.4%孔隙率的非常多孔结构。X 射线粉末衍射和差示扫描量热法数据表明，部分晶型药物转化为无定形形式。在 40°C/75%RH 下，打印片稳定，含量和溶解度无明显变化。打印片和压缩片剂的药代动力学曲线相似。总之，INH 的速溶打印片稳定，口服生物利用度与成分相同的压缩片剂相似。
