Granulation
When powder properties are unsuitable for direct compression, a granulation step is required to improve compactibility, flow, and content uniformity.
Lipid excipients are commonly used in two granulation techniques to modify drug dissolution, either as sustained-release or wetting agents:
- wet granulation—where the solid lipid excipient is used in the powder blend or incorporated into the binder solution
- melt granulation—where the lipid excipient acts as a binder between the solid particles (ingredients are blended as temperature is brought gradually up to the lipid melting point to form granules)
Advantages of lipid excipients in wet granulation:
- organic solvent–free process
- water-insoluble atomized powders prevent swelling and sticking during granulation
- waxy, water-dispersible Gelucires incorporated into aqueous binder solution
- easy cleaning of equipment and tooling
Advantages of lipid excipients in melt granulation:
- solvent-free process
- high binding capacity, yielding resistant granules
- flexible process, suitable for high shear mixer, melt extruder, and fluid bed granulator
Range of functional excipients for granulation:
- Modified-release agents (reported level of use: 10%–40%)
- Wetting agents (reported level of use: 15%–25%)
A Gattefossé in-house study of continuous granulation via extrusion has demonstrated that
- hot melt granulation is achievable using a twin-screw extruder simply without the die;
- granule particle size can easily be adjusted by adapting the extrusion temperature profile and feed rate.
Two cases studies are available:
- ibuprofen / Compritol® 888 ATO (9:1 ratio)
- tramadol hydrochloride / Compritol® 888 ATO
Watch the video on continuous granulation with Precirol® ATO 5