Department of Mechanical and Aerospace Engineering, Rutgers University, 98 Brett Road, Piscataway, New Jersey, 08854, USA.
Center for structured organic particulate systems, Rutgers University, New Brunswick, New Jersey, USA.
AAPS PharmSciTech. 2019 Apr 16;20(5):168. doi: 10.1208/s12249-019-1369-0.
In this work, the effect of API's (Active Pharmaceutical Ingredient) shape and size on tablet characteristics is investigated for high API dose formulation manufactured by direct compression. Three different classes of APAP (acetaminophen) are selected, and tablets are produced in both single and batch processes. After performing and comparing comprehensive series of standard characterization tests including hardness, dissolution, disintegration, and friability on the tablets, the test results show the relation between the quality of APAP tablets and the shape and size of the crystals. We also investigate the effect of scaling up the manufacturing process (from single to batch) by evaluating dosage uniformity and possibility of segregation in blends. The results indicate a strong interaction between manufacturing parameters such as speed and scale of production to API crystal size and shape. This places crystal properties in the critical parameter set that requires tracking and monitoring in order to maintain consistent tablet properties in high-dose formulation continuous manufacturing operations.
在这项工作中，研究了 API（活性药物成分）的形状和大小对直接压缩法制备高 API 剂量配方片剂特性的影响。选择了三种不同类别的对乙酰氨基酚（APAP），并在单批和批处理过程中生产片剂。在对片剂进行了包括硬度、溶出度、崩解度和脆碎度在内的一系列综合标准特性测试后，测试结果表明 APAP 片剂的质量与晶体的形状和大小之间存在关系。我们还通过评估剂量均匀性和混合物中分离的可能性，研究了放大制造工艺（从单批到批处理）的效果。结果表明，生产参数（如生产速度和规模）与 API 晶体大小和形状之间存在强烈的相互作用。这使得晶体特性成为关键参数组，需要进行跟踪和监控，以在高剂量配方连续制造操作中保持一致的片剂特性。
