2.9.41. 颗粒和微丸的脆碎度

01/2008:209412.9.41. Friability of granules and spheroids 2.9.41.颗粒和微丸的脆碎度2.9.41. Friability of granules and spheroidsThis chapter describes 2 methods for determination of the friability of granules and spheroids, which may be used during development studies. It is recognised, however, that many methods with equal suitability may be used. This test is intended to determine, under defined conditions, the friability of granules and spheroids. 2.9.41.颗粒和微丸的脆碎度本章节描述了2种测定颗粒和微丸的脆碎度的方法，该方法可用于研发期间。这是公认的，但是，同样有多种适合的方法可以使用。这个测试的目的是确定在特定的条件下，颗粒和微丸脆碎度。Friability is defined as a reduction in the mass of the granules or spheroids or in the formation of fragments of granules or spheroids, occurring when the granules or spheroids are subjected to mechanical strain during handling (tumbling, vibration, fluidisation, etc.). Examples of changes are abrasion, breakage or deformation of granules or spheroids.脆碎度的定义是指当颗粒或微丸受到机械应力处理期间（翻滚，振动，流化等），颗粒或微丸或颗粒碎片或微丸碎片出现质量方面的减少。例如颗粒或微丸的磨损、破损、变形。METHOD A方法AApparatus (fluidised-bed apparatus). 装置（流化床装置）The apparatus (see Figure 2.9.41.-1) consists of a glass cylinder (A) with a conical lower part. The cylinder is provided with a sieve lid (B) having an aperture size of 500m or any other suitable sieve. The conical end is connected to a U-shaped glass tube (C) that can be disconnected from the cylinder for removal of the granules or spheroids. 该装置（见图2.9.41.-1）包含一个下部呈圆锥形的玻璃圆筒（A）。圆筒拥有一个筛孔尺寸为500m的筛网盖子（B）或其他任何合适的筛子。锥形端连接了一个可与圆筒分离的U形玻璃管（C），用于取出颗粒或微丸。The U-tube is attached to a T-coupling (D). One inlet of the T-coupling is joined by a silicone tube to a manometer for regulating the compressed-air flow (use compressed air complying with the test for water in the monograph Medicinal air (1238), the other one is connected via a silicone tube to a by-pass flowmeter (E) (0.10-1.00 m3h1).U形管连接到一个T-联管节（D）。T -联管节的一个入口连接了一个通过硅胶管相连的压力计，用于调节压缩空气流量（使用压缩空气应遵循药用空气专著（1238）对水分的进行测验），另一个入口是通过硅胶管连接到旁路流量计(E) (0.10-1.00 m3h1).Figure 2.9.41.-1 Fluidised-bed apparatus图2.9.41.-1. 流化床装置Procedure. 步骤 The following procedure is usually suitable. Remove the fine particles by sieving (sieve having an aperture size of 710 m or any other suitable sieve). Introduce about 8.0 g (m1) of granules or spheroids into the cylinder (A). Close the apparatus with the sieve lid (B).下面的过程通常是比较适用。通过筛分去除细颗粒（筛孔尺寸为710m或其他任何适宜的筛子）取约8g(m1)的颗粒或微丸置圆筒（A）内。盖上筛盖（B）。Adjust the flow rate of the compressed air to 0.45 m3h1. After 15 min, remove the granules or spheroids from the apparatus by disconnecting the U-tube and weigh again (m2). Test 3 samples and calculate the mean value. It is recommended to spray the inside of the apparatus with an antistatic agent every 3 determinations in order to prevent electrostatic charging.调整压缩空气流速至0.45 m3h1.15分钟后，通过分离U形管取出颗粒或微丸，再次称量(m2).测试3份样品，计算其平均值。为了预防静电，推荐每测定3次在装置内喷射抗静电剂。Loss on drying. Dry in an oven at 105 C, unless otherwise prescribed. Alternatively, other drying conditions as described in general method 2.2.32 may be used.干燥失重除另有规定外，在105 C烘箱干燥。另外，通用方法2.2.32中描述的其他干燥条件也可以使用。CalculationF = friability; T1 = percentage loss on drying before the test (mean of 2 determinations); T2 = percentage loss on drying after the test (mean of 2 determinations); m1 = mass of the granules or spheroids before the test, in grams; m2 = mass of the granules or spheroids after the test, in grams. 计算F =脆碎度T1 =测试前的干燥失重百分比（2次测定的平均值）T2 =测试后的干燥失重百分比（2次测定的平均值）m1 =测试前颗粒或微丸的质量，以g为单位；m2 =测试后颗粒或微丸的质量，以g为单位；METHOD B方法BApparatus (oscillating apparatus). 装置（振荡装置）The apparatus (see Figure 2.9.41.-2) consists of a 105 mL glass container, containing the granules or spheroids to be examined, which is subjected to horizontal oscillations. The frequency and duration of the oscillations can be varied continuously.The frequency can be adjusted, using a scale, to a value in the range 0-400 oscillations/min. The duration can be set to a value in the range 0-9999 s.该装置（见图2.9.41.-2）包含一个105ml的玻璃容器，容纳待检查的颗粒或微丸，承受水平振荡。振荡频率和持续时间可不断改变。振荡频率可通过刻度盘在0-400次/分钟的范围内进行调整。持续时间可在0-9999秒范围内进行设置。图2.9.41.-2. 振荡装置Procedure. 步骤The following procedure is usually suitable. Remove the fine particles by sieving (sieve having an aperture size of 355 m or any other suitable sieve). In the glass container, weigh about 10.00 g (m1) of the granules or spheroids. Install the container in the apparatus.下面的过程通常是比较适用。通过筛分去除细颗粒（筛孔尺寸为355m或其他任何适宜的筛子）称取约10.00g（m1）颗粒或微丸，置玻璃容器中。将容器安装在振荡装置上。Shake for 240 s at the highest frequency for hard granules or spheroids, or for 120 s at a lower frequency (e.g. 140 oscillations/min) for soft granules or spheroids. Sieve (355 m, or the same sieve as used previously) and weigh the granules or spheroids again (m2). Test 3 samples and calculate the mean value.硬的颗粒或微丸采用高频振荡240s，软的颗粒或微丸采用低频（eg：140振荡次数/分钟）振荡120s。筛分（355 m,或前面使用过的同一筛子），并称取颗粒或微丸重量(m2)。测试3份样品，计算其平均值。Loss on drying. Dry in an oven at 105 C, unless otherwise prescribed. Alternatively, other drying conditions as described in general method 2.2.32 may be used.干燥失重除另有规定外，在105 C烘箱干燥。另外，通用方法2.2.32中描述的其他干燥条件也可以使用。CalculationF = friability; T1 = percentage loss on drying before the test (mean of 2 determinations); T2 = percentage loss on drying after