A novel methodology to study polymodal particle size distributions produced during continuous wet granulation

作者：Torrecillas Carlota Mendez^*; Halbert Gavin W; Lamprou Dimitrios A^*

来源：International Journal of Pharmaceutics, 2017, 519(1-2): 230-239.

DOI：10.1016/Apharm.2017.01.023

• Twin screw granulation
• Particle size distribution
• Homogeneity factor
• Quality by design
• Granules

It is important during powder granulation to obtain particles of a homogeneous size especially in critical situations such as pharmaceutical manufacture. To date, homogeneity of particle size distribution has been defined by the use of the d(50) combined with the span of the particle size distribution, which has been found ineffective for polymodal particle size distributions. This work focuses on demonstrating the limitations of the span parameter to quantify homogeneity and proposes a novel improved metric based on the transformation of a typical particle size distribution curve into a homogeneity factor which can vary from 0 to 100%. The potential of this method as a characterisation tool has been demonstrated through its application to the production of granules using two different materials. The workspace of an 11 mm twin screw granulator was defined for two common excipients (alpha-lactose monohydrate and microcrystalline cellulose). Homogeneity of the obtained granules varied dramatically from 0 to 95% in the same workspace, allowing identification of critical process parameters (e.g. feed rate, liquid/solid ratio, torque velocities). In addition it defined the operational conditions required to produce the most homogeneous product within the range 5 mu m-2.2 mm from both materials.

• 出版日期2017-3-15