Dissolve drug in solution containing polymer and then

Dissolve drug in solution containing polymer and then spray this onto the beads
 Reasons:
o To bond different ingredients together and prevent segregation to control content uniformity
and blend uniformity attributes
o To improve flow properties of the powder blend,
 Increase bulk density and increase particle size
 Improve particle shape
 Control percentage of fine particles
o To improve mechanical properties of high dose tablets whose active ingredient is poorly
compactable
 If high doses have compacting issues, you’re limited on how mechanically strong
you can make it

o To increase powder wetting characteristics and dissolution rate of hydrophobic drugs
o If you have a lower percentage of AI in formulation, you can do this to bond them together
with other excipients
 Reduces risk of segregation during the process
o If you have high concentration of the drug but it doesn’t have favorable morphology, it won’t
flow well
 Shouldn’t be issue with low dose because all excipients can be purchased in a grade
that’s highly flowable
o Mechanical properties are necessary to make a strong product and can be affected at high dose
tablets
o Hydrophobic compounds may need a hydrophilic spray or surfactant to get an easily wetting
material on the surface of your hydrophobic drug and overall better wetting properties
 Desirable granule properties:
o Spherical or low aspect ratio shape
 Spheres have aspect ratio of 1
 Closer to 1, the better the flow
o Higher density than initial component powders
o Controlled and relatively narrow size distribution
 Can only tolerate a small amount of fine particles
 Maintains interparticle voids
o Appropriate mechanical strength
 Sufficiently strong to remain granulator through subsequent steps
 Granule breakdown reduces flow
o Controlled moisture content
o Highly compactable
o Readily wetting
 Sometimes put hydrophilic material outside hydrophobic drug
7. Understanding the mechanism and bonding steps involved in wet and dry granulation
 Wet granulation
o More likely to produce higher density and more spherical granules
o Easier to achieve uniform drug distribution for low dose products
o Requires a dry step to remove granulation fluid
o Goal overall is to reduce the likelihood that we’re going to have segregation of the drug
o Desirable binder properties:
 Cohesive
 Strong glue to bind powders together after drying
 Chemically inert
 Nonreactive with drug
 Quickly dissolving during solution preparation
 If you are going to dissolve it
 Easily sprayed
 Low viscosity, low surface tension
o Form very fine droplets when you spray it
 Hydrophilic
 Promote rapid wetting of fine granules and drug dissolution
o Granulation solvent
 Water is used whenever possible
 Disadvantages:
o Potential hydrolysis of AI
o Potential hydrate or amorphous formation of drug crystals

o Requires longer drying time than organic solvents
 Alternatives for water-sensitives drugs: alcohols or organic solvents, solvate or