Determining the Impact of Roller Compaction Processing Conditions on Granule and API Properties
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Research Article Determining the Impact of Roller Compaction Processing Conditions on Granule and API Properties James Clarke,1 John F. Gamble,2,4 John W. Jones,2 Mike Tobyn,2 Neil Dawson,3 Conrad Davies,3 Andrew Ingram,1 and Richard Greenwood1
Received 9 June 2020; accepted 22 July 2020 Abstract. The attrition of drug particles during the process of dry granulation, which may (or may not) be incorporated into granules, could be an important factor in determining the subsequent performance of that granulation, including key factors such as sticking to punches and bio-performance of the dosage form. It has previously been demonstrated that such attrition occurs in one common dry granulation process train; however, the fate of these comminuted particles in granules was not determined. An understanding of the phenomena of attrition and incorporation into granule will improve our ability to understand the performance of granulated systems, ultimately leading to an improvement in our ability to optimize and model the process. Unique feeding mechanisms, geometry, and milling systems of roller compaction equipment mean that attrition could be more or less substantial for any given equipment train. In this work, we examined attrition of API particles and their incorporation into granule in an equipment train from Gerteis, a commonly used equipment train for dry granulation. The results demonstrate that comminuted drug particles can exist free in post-milling blends of roller compaction equipment trains. This information can help better understand the performance of the granulations, and be incorporated into mechanistic models to optimize such processes. KEY WORDS: attrition; particle size; morphologically directed Raman spectroscopy; roller compaction; pharmaceuticals.
INTRODUCTION Roller compaction is a common unit operation (1,2) used in the pharmaceutical industry to improve the flow properties of powders prior to tableting (3). Typically, a formulated blend consisting of active pharmaceutical ingredients (API) and excipients is compacted between two counter-rotating rolls under pressure to form a ribbon which is subsequently milled to give granule. Roller compaction does not require the use of liquid binder or a drying stage, and unlike wet granulation, can be used for heat and moisture sensitive API. In comparison with wet granulation, dry granulation typically results in granulate which contains a notably higher volume of fines which are generally thought to be beneficial (4–8), although there are examples where the minimization of fines was demonstrated to be beneficial to downstream performance (9). 1
School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, UK. 2 Bristol Myers Squibb, Reeds Lane, Moreton, Wirral, CH46 1QW, UK. 3 Pfizer, Discovery Park, Ramsgate Road, Sandwich, CT13 9ND, UK. 4 To whom correspondence should be addressed. (e–mail: [email protected])
The design and control of API particle characteristics, in particular the control of API particle size and habit with respect to the
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