Lenz Jan, Finke Jan Henrik, Bunjes Heike, Kwade Arno, Juhnke Michael
Novartis Pharma AG, Fabrikstrasse 2, CH-4056 Basel, Switzerland.
Technische Universität Braunschweig, Institut für Partikeltechnik, Volkmaroder Strasse 5, D-38104 Braunschweig, Germany.
Int J Pharm X. 2021 Nov 2;3:100103. doi: 10.1016/j.ijpx.2021.100103. eCollection 2021 Dec.
The functional behaviour of tablets is strongly influenced by their manufacturing process and the choice of excipients. Water uptake and swelling are prerequisites for tablet disintegration, dispersion and hence active pharmaceutical ingredient (API) dissolution. High proportions of polymeric excipients in tablets, which are typically used as API carriers in amorphous solid dispersions (ASDs), may be challenging due to the formation of a gelling polymer network (GPN). In this study, systematic investigations into the formulation development of tablets containing polymeric and other excipients are performed by water uptake and swelling analysis. The impact of tablet composition and porosity as well as pH of the test medium are investigated. The pH affects the analysis results for Eudragit L100-55 and Eudragit EPO. HPMC and Kollidon VA64 inhibit water uptake and swelling of tablets due to the formation of a GPN. High tablet porosity, coarse particle size of the polymer and the addition of fillers and disintegrants can reduce the negative impact of a GPN on tablet performance. The application of lubricants slows down the analysed processes. Water uptake and swelling data are fitted to an empirical model obtaining four characteristic parameters to facilitate the simple quantitative assessment of varying tablet formulations and structural properties.
片剂的功能行为受到其制造工艺和辅料选择的强烈影响。吸水和溶胀是片剂崩解、分散以及活性药物成分(API)溶解的先决条件。片剂中高比例的聚合物辅料(通常在无定形固体分散体(ASD)中用作API载体)由于形成凝胶聚合物网络(GPN)可能具有挑战性。在本研究中,通过吸水和溶胀分析对含有聚合物和其他辅料的片剂配方开发进行了系统研究。研究了片剂组成、孔隙率以及测试介质pH值的影响。pH值会影响Eudragit L100 - 55和Eudragit EPO的分析结果。羟丙甲纤维素(HPMC)和共聚维酮(Kollidon VA64)由于形成GPN而抑制片剂的吸水和溶胀。高片剂孔隙率、聚合物的粗粒度以及添加填充剂和崩解剂可以减少GPN对片剂性能的负面影响。润滑剂的应用会减缓所分析的过程。将吸水和溶胀数据拟合到一个经验模型中,得到四个特征参数,以便于对不同片剂配方和结构性质进行简单的定量评估。