Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark; ET Oral Product Development, Novo Nordisk A/S, Måløv, Denmark.
ET Oral Product Development, Novo Nordisk A/S, Måløv, Denmark.
Int J Pharm. 2023 Jul 25;642:123165. doi: 10.1016/j.ijpharm.2023.123165. Epub 2023 Jun 24.
Roller compaction before tableting is a common unit operation to increase the processability of powders. Terahertz time-domain spectroscopy (THz-TDS) has recently been introduced as a potential process analytical technology (PAT) for measuring tablet porosity based on the refractive index of the tablet. Tablet porosity is a governing parameter for tablet disintegration and dissolution. The first aim of this study was to investigate tablets prepared from roller-compacted materials with THz-TDS to explore its usefulness for particle size evaluation of granules in tablets. Secondly, the impact of roller compaction and granule size before tablet compression on the established THz-TDS based measurement of tablet porosity was investigated. Microcrystalline cellulose and α-lactose monohydrate were roller compacted separately at five specific compaction forces (2, 4, 8, 12, and 16 kN cm) and fractionated into three size fractions. Tablets were prepared from the fractionated and unfractionated granules at twelve tableting pressures and subjected to THz-TDS transmission measurements. It was possible to use the scattering behaviour of the tablets at terahertz frequencies to describe the granulated materials' particle size changes during tableting. At the same time, prediction of porosity was impaired due to the deviation of the refractive index in strongly scattering samples. A correction method was introduced in which the porosity error was corrected based on the tablet's scattering behaviour, resulting in an improved prediction of tablet porosity. In conclusion, THz-TDS is considered a promising technique for the process monitoring of tableting based on its sensitivity to porosity and particle size changes within the tablet non-destructively, with a possible application as part of an in-process control strategy of the tableting of granulated or non-granulated materials.
压片前的辊压是一种常见的单元操作，可提高粉末的可加工性。太赫兹时域光谱（THz-TDS）最近被引入作为一种潜在的过程分析技术（PAT），用于基于片剂的折射率测量片剂的孔隙率。片剂孔隙率是控制片剂崩解和溶解的参数。本研究的首要目的是用 THz-TDS 研究从辊压材料制备的片剂，以探索其在片剂中颗粒粒度评估中的有用性。其次，研究了辊压和压片前颗粒大小对基于 THz-TDS 的片剂孔隙率测量的影响。微晶纤维素和α-乳糖一水合物分别在五个特定的压实力（2、4、8、12 和 16 kN·cm）下进行辊压，并分成三个粒度级分。将分级和未分级的颗粒在十二个压片压力下制备成片剂，并进行 THz-TDS 透射测量。可以使用片剂在太赫兹频率下的散射行为来描述压片过程中颗粒材料的粒度变化。同时，由于强烈散射样品的折射率偏差，预测孔隙率的能力受到影响。引入了一种校正方法，其中根据片剂的散射行为校正孔隙率误差，从而改善了片剂孔隙率的预测。总之，THz-TDS 被认为是一种有前途的技术，可用于基于其对片剂内部孔隙率和粒度变化的敏感性进行压片过程监测，有可能作为颗粒或非颗粒材料压片过程中过程控制策略的一部分。
