Novo Nordisk A/S, Oral Pilot and Process Development, Måløv, Denmark; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
Int J Pharm. 2020 Sep 25;587:119645. doi: 10.1016/j.ijpharm.2020.119645. Epub 2020 Jul 14.
Drug release performance of tablets is often highly dependent on disintegration, and water ingress is typically the rate-limiting step of the disintegration process. Water ingress into tablets is known to be highly influenced by the microstructure of the tablet, particularly tablet porosity. Initial particle size distribution of the formulation and the predominant powder deformation behaviour during compression are expected to impact such microstructure, making both factors important to investigate in relation to water ingress into tablets. Two size fractions (<125 and 355-500 µm) of plastically deforming microcrystalline cellulose (MCC) and fragmenting di-calcium phosphate (DCP) were compressed into tablets with porosities ranging from 5 to 30% (with 5% increments). The total porosity of the tablets was measured using terahertz time-domain spectroscopy and liquid transport into these tablets was quantified using a flow cell coupled to terahertz pulsed imaging. It was found that tablets compressed from large MCC particles resulted in slower water ingress compared to tablets prepared from small MCC particles. In contrast, no difference in liquid transport kinetics was observed for tablets prepared across both size fractions of DCP particles. These results highlight the complex interplay between material characteristics, the process induced microstructure, and the liquid transport process that ultimately determines the drug release performance of the tablets.
片剂的药物释放性能通常高度依赖于崩解，而水的侵入通常是崩解过程的限速步骤。已知片剂的微观结构，特别是片剂的孔隙率，对水的侵入有很大影响。配方的初始粒径分布和压缩过程中主要的粉末变形行为预计会影响这种微观结构，这两个因素都与片剂中水的侵入有关，需要进行研究。将塑性变形的微晶纤维素（MCC）和碎裂的磷酸二钙（DCP）的两个粒径分数（<125 和 355-500 µm）压缩成具有 5-30%（每次增加 5%）孔隙率的片剂。使用太赫兹时域光谱法测量片剂的总孔隙率，并使用与太赫兹脉冲成像耦合的流动池定量测量这些片剂中的液体传输。结果发现，与由小 MCC 颗粒制备的片剂相比，由大 MCC 颗粒压缩的片剂的水侵入速度较慢。相比之下，对于由 DCP 颗粒的两个粒径分数制备的片剂，没有观察到液体传输动力学的差异。这些结果突出了材料特性、过程诱导的微观结构以及最终决定片剂药物释放性能的液体传输过程之间的复杂相互作用。
