Eriksson H J C, Hinrichs W L J, van Veen B, Somsen G W, de Jong G J, Frijlink H W
Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Int J Pharm. 2002 Dec 5;249(1-2):59-70. doi: 10.1016/s0378-5173(02)00531-8.
The aim of this study was to investigate the formulation of sugar glass stabilised alkaline phosphatase from bovine intestine (BIAP) into tablets. Two major subjects of tablet formulation were investigated. First, the compaction behaviour of the inulin sugar glass was investigated. Secondly, the effect of the compaction process on the physical stability of sugar glass stabilised BIAP was investigated, comparing inulin and trehalose glass. The tabletting properties of freeze-dried inulin without BIAP were studied first. Freeze-dried inulin conditioned at either 20 degrees C/0% relative humidity (RH) or 20 degrees C/45% RH was compacted at various pressures. As expected, the yield pressure of the material conditioned at 0% RH was higher (68 MPa) than after conditioning at 45% RH (39 MPa). Tablets made of the material stored at 0% RH showed severe capping tendency, especially at high compaction pressures. In contrast, material conditioned at 45% RH gave tablets without any capping tendency and a friability of less than 1%. Sugar glasses of BIAP and either inulin or trehalose were prepared by freeze-drying (BIAP/sugar 1/19 (w/w)). The material was subsequently compacted. Tablets and powders were stored at 60 degrees C/0% RH. The activity of the incorporated BIAP was measured at various time intervals. It was found that inulin was by far superior to trehalose as stabiliser of BIAP in tablets. The poor stabilising capacities of trehalose after compaction are explained by crystallisation of trehalose induced by the compaction process and moisture in the material. The results clearly show that inulin is an excellent stabiliser for BIAP. The tabletting properties are adequate, showing sufficient tablet strengths and low friability. Furthermore, the good (physical) stability of inulin glass with respect to exposure to high relative humidities makes it practical to work with.
本研究的目的是研究将牛肠碱性磷酸酶（BIAP）制成的糖玻璃制剂压制成片剂的方法。研究了片剂配方的两个主要方面。首先，研究了菊粉糖玻璃的压缩行为。其次，研究了压缩过程对糖玻璃稳定的BIAP物理稳定性的影响，并比较了菊粉和海藻糖玻璃。首先研究了不含BIAP的冻干菊粉的压片性能。将在20℃/0%相对湿度（RH）或20℃/45%RH条件下处理的冻干菊粉在不同压力下压片。正如预期的那样，在0%RH条件下处理的材料的屈服压力（68MPa）高于在45%RH条件下处理后的屈服压力（39MPa）。由储存在0%RH的材料制成的片剂显示出严重的裂片倾向，尤其是在高压缩压力下。相比之下，在45%RH条件下处理的材料制成的片剂没有任何裂片倾向，脆碎度小于1%。通过冷冻干燥制备BIAP与菊粉或海藻糖的糖玻璃（BIAP/糖1/19（w/w））。随后将该材料压片。片剂和粉末储存在60℃/0%RH条件下。在不同时间间隔测量掺入的BIAP的活性。结果发现，在片剂中，菊粉作为BIAP的稳定剂远比海藻糖优越。压缩后海藻糖的稳定能力差是由于压缩过程和材料中的水分诱导海藻糖结晶所致。结果清楚地表明，菊粉是BIAP的优良稳定剂。其压片性能良好，片剂强度足够且脆碎度低。此外，菊粉玻璃在高相对湿度下具有良好的（物理）稳定性，便于实际操作。
