A methodological approach to define the regime map boundaries does not exist, and while some experimental data has been reported previously the boundaries have not been “validated”. The present study explored and quantified the boundary between the nucleation and induction growth regimes for a model high drug load formulation. It was postulated that the induction period could be decreased by increasing the liquid saturation of the system, with the effect of introducing additional binder liquid to the surface of the granules, which facilitates consolidation and growth. An increase in liquid saturation was achieved by increasing the liquid to solid ratio, or by densifying the granules to squeeze intragranular liquid to the surface. The densification was achieved by subjecting the granules to an extended wet massing period and by varying the impeller speed. By characterizing the response in granule porosity as a function of liquid to solid ratio, wet massing time and impeller speed the boundary between the nucleation and induction growth regimes was defined. Granules formed in the induction growth regime were shown to suffer significantly reduced compactibility. Further analysis of liquid saturation and compactibility data allows a critical granule porosity to be established as a basis for developing a control strategy. The attention to granule porosity allows a mechanistic interpretation of the growth behavior, rather than simply relying upon size measurements. The porosity based approach was successfully superimposed onto the existing growth regime map framework, and established that the boundary between regimes is a gradual transition rather than the conventionally visualized abrupt binary state.

尚没有定义状态映射图边界的方法学方法，尽管先前已报告了一些实验数据，但尚未对边界进行“验证”。本研究探索并定量了模型高药物负荷配方的成核和诱导生长方案之间的边界。据推测，可以通过增加体系的液体饱和度来缩短诱导期，其效果是将额外的粘合剂液体引入颗粒表面，从而有利于固结和生长。通过增加液固比或通过将颗粒致密化以将颗粒内液体挤压至表面来实现液体饱和度的增加。通过使颗粒经受延长的湿法成团期并通过改变叶轮速度来实现致密化。通过表征颗粒孔隙率的响应，作为液/固比，湿质量时间和叶轮速度的函数，定义了成核和感应生长机制之间的边界。在诱导生长方案中形成的颗粒显示出紧密度显着降低。液体饱和度和可压实性数据的进一步分析允许建立关键的颗粒孔隙率，作为制定控制策略的基础。对颗粒孔隙率的关注允许对生长行为进行机械解释，而不是仅仅依靠尺寸测量。基于孔隙率的方法已成功地叠加到现有的生长机制图框架中，