Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation

Transcription

1 Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Shantanu Sonparote AbbVie Associate Process Development Engineer, AbbVie Manufacturing Science & Technology March 18, 2014 Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 1

2 Outline Basics of roller compaction Market trends & benefits of Roller Compaction Example Process Development Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 2

3 Basics: What is Roller Compaction? Dry Granulation technique; no liquid is present A powder blend is pressed together between rollers to form a ribbon Rollers Mill Ribbons then pass through a mill, breaking them into granules Granulation is necessary to improve the physical characteristics of the blend, such as flow, compressibility, etc. Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 3

4 Roller Compaction Advantages Disadvantages Doesn t involve moisture More flexibility with compounds Economical: Eliminates drying step Technical ease in scalability Removes some plastic deformation Minimal mixing Very dependent on material properties Production Consistency Content Uniformity of API Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 4

5 Roller Compaction Role in Potent Manufacturing Potent compounds tend to have a lower drug loading Therefore Low drug loading allows more control of material properties via excipient selection! Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 5

6 Challenges of Potent Roller Compaction Material Transfer Cleaning Process characterization Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 6

7 Dispensing Blending Example Process Roller Compaction Final Blend Compression

8 API Dispensing Isolators must be used to charge neat API into an Intermediate Bin Container (IBC) Container Dock Split Butterfly Valve This requires additional dispensing time, and more care must be taken to ensure the API is fully transferred Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 8

9 Blending & Charging Materials remain in the IBC throughout blending process To minimize potent exposure the IBC is also used as the vessel to charge the Roller Compactor Effective transfer is done through the use of a splitbutterfly valve Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 9

10 Roller Compaction Startup The split butterfly valve is open and the roller compaction is started Powder material is fed into the roller compactor via tamping and feed augers The powder is pressed between two rollers forming ribbons, then milled The milled granules are discharged through another split butterfly valve into a receiving IBC Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 10

11 Roller Compaction Sampling When developing a roller compaction process, it is beneficial to collect samples at two points in the roller compactor: Ribbon Samples Granule Samples Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 11

12 Roller Compaction Sampling Contained sampling is required; may require unique solutions to be developed/customized based on product requirements Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 12

13 Process Characterization via Testing Testing equipment is contained within an Isolator Ribbon samples can be tested for envelope density Envelope density provides an understanding of ribbon quality and granule compressibility Too low of density results in poor quality ribbons, that may revert back to loose powder Too high of density results in higher density granules, which may reduce future compressibility when forming tablets Particle size, bulk and tap density on granule samples Particle size data can be used to characterize the material, gauge flowability, and understand the consistency of granulation Testing gives quantified results that can ensure effective tech transfers Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 13

14 Cleaning Utilize WIP/CIP Equipment WIP/CIP system connects to spray bulbs within the roller compactor chamber Surfactants may be used depending on product need Cleaning studies are done before work begins; upon completion, equipment is swabbed and tested after washing to ensure no residue remains on the equipment Mitigates risk of dry powder when disassembling equipment Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 14

15 Scalability Granules can be produced at both pilot scale and commercial scales Scale-up is simple: a longer run time will produce more material This allows the process to be optimized throughout the development lifecycle and eases transfer into commercial manufacturing Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 15

16 Conclusions Dry granulation via roller compaction is a suitable method for manufacturing potent drug products Benefits include: - Effective at processing APIs at low levels - Simplicity of scale-up - Ease of tech transfer Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 16

17 Acknowledgements Liam Feely Jaqueline Wardrop Michelle Calhoun Brian C. Anderson Karen Florjancic Clark Richards Patrick Cashman Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation Interphex 2014 Date Copyright 2014 AbbVie 17

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