做为药物层积载体的糖丸的稳健性检测相关方法的评价.PDFVIP

Evaluation of a Process Relevant Method for Determining the AAPS Poster Reprint 2014 Robustness of Sugar Spheres as a Drug Layering Substrate Scott Vass, Charles Cunningham and Ali Rajabi-Siahboomi Colorcon, Inc., Harleysville, PA USA Purpose The mechanical strength, particle size and sphericity of starting sugar spheres for drug layering and subsequent functional coating applications are critical to achieving a reproducible and high yield final product.1 During early processing, spheres can be subjected to high mechanical stress that may result in the generation of fines, changes in particle size and loss of sphericity. The European Pharmacopoeia describes both a fluidization apparatus and an oscillating apparatus method for determining the friability of granules and spheroids.2 The oscillating method was shown by Christiansen et. al. to be more suitable for consistently determining the friability of pellets over a wide range of hardness.3 These friability methods however may not be fully indicative of mechanical stresses in a production environment. The objective of this study was to evaluate the mechanical robustness of SUGLETS® sugar spheres using the oscillating friability method as compared to attrition values generated in laboratory and production scale fluid bed processes. Methods Sugar spheres of 20/25 mesh (710-850µm, Suglets® PF010, Colorcon Inc., USA) were used as the substrate. Laboratory friability testing of the sugar spheres was performed using a modified methodology based on Eur. Ph. 2.9.41, Method B. The equipment used is shown in Figure 1. Figure 1. Oscillating Friability Apparatus (Erweka GTA 120, Milford, CT, USA) In this method, 10 g of spheres were weighed into the glass container along with 25 g of glass beads (2 mm). The container was subjected to oscillatio