A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes

Publication date: 10 July 2018 Source:International Journal of Pharmaceutics, Volume 545, Issues 1–2 Author(s): N. Willecke, A. Szepes, M. Wunderlich, J.P. Remon, C. Vervaet, T. De Beer The overall objective of this work is to understand how excipient characteristics influence the drug product quality attributes and process performance of a continuous twin screw wet granulation process. The knowledge gained in this study is intended to be used for Quality by Design (QbD)-based formulation design and formulation optimization. Three principal components which represent the overarching properties of 8 selected pharmaceutical fillers were used as factors, whereas factors 4 and 5 represented binder type and binder concentration in a design of experiments (DoE). The majority of process parameters were kept constant to minimize their influence on the granule and drug product quality. 27 DoE batches consisting of binary filler/binder mixtures were processed via continuous twin screw wet granulation followed by tablet compression. Multiple linear regression models were built providing understanding of the impact of filler and binder properties on granule and tablet quality attributes (i.e. 16 DoE responses). The impact of fillers on the granule and tablet responses was more dominant compared to the impact of binder type and concentration. The filler properties had a relevant effect on granule characteristics, such as particle size, friability and specific surface area. Binde...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research