Potent Manufacturing of Solid Oral Dosages Utilizing Dry ...€¦ · • Dry Granulation technique;...

Potent Manufacturing of Solid Oral Dosages Utilizing Dry Granulation | Interphex 2014| Date 4.18.2014 | Copyright © 2014 AbbVie 1

Potent Manufacturing of Solid Oral Dosages Utilizing

Dry Granulation

Shantanu Sonparote

AbbVie Associate Process Development Engineer, AbbVie Manufacturing Science & Technology

March 18, 2014


• Basics of roller compaction

• Market trends & benefits of Roller Compaction

• Example Process Development

Outline


• Dry Granulation technique; no liquid is present

• A powder blend is pressed together between rollers to form a ribbon

• 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.

Basics: What is Roller Compaction?

Mill

Rollers


Advantages

• Doesn’t involve moisture

• More flexibility with compounds

• Economical: Eliminates drying step

• Technical ease in scalability

• Production Consistency

• Content Uniformity of API

Disadvantages

• Removes some plastic deformation

• Minimal “mixing”

• Very dependent on material properties

Roller Compaction


Potent compounds tend to have a lower drug loading

Roller Compaction – Role in Potent Manufacturing

Low drug loading allows more control of material properties via excipient selection!

Therefore…


Material Transfer

Process characterization

Cleaning

Challenges of Potent Roller Compaction

Example Process

Dispensing

Blending

Roller Compaction

Final Blend

Compression


Isolators must be used to charge neat API into an Intermediate Bin Container (IBC)

This requires additional dispensing time, and more care must be taken to ensure the API is fully transferred

API Dispensing

Container Dock

Split Butterfly Valve


• 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 split-butterfly valve

Blending & Charging


• 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

Roller Compaction Startup


When developing a roller compaction process, it is beneficial to collect samples at two points in the roller compactor:

Roller Compaction Sampling

Ribbon Samples

Granule Samples


Contained sampling is required; may require unique solutions to be developed/customized based on product requirements

Roller Compaction Sampling


Testing equipment is contained within an Isolator

• 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

Ribbon samples can be tested for envelope density

• Particle size data can be used to characterize the material, gauge flowability, and understand the consistency of granulation

Particle size, bulk and tap density on granule samples

Testing gives quantified results that can ensure effective tech transfers

Process Characterization via Testing


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

Cleaning


• 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

Scalability


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


Liam Feely

Jaqueline Wardrop

Michelle Calhoun

Brian C. Anderson

Karen Florjancic

Clark Richards

Patrick Cashman

Acknowledgements

Potent Manufacturing of Solid Oral Dosages Utilizing Dry ...€¦ · • Dry Granulation technique;...

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