Dissolve drug in solution containing polymer and then spray this onto the beads

Dissolve drug in solution containing polymer and then

This preview shows page 6 - 9 out of 17 pages.

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
Image of page 6
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
Image of page 7
o Requires longer drying time than organic solvents Alternatives for water-sensitives drugs: alcohols or organic solvents, solvate or
Image of page 8
Image of page 9

You've reached the end of your free preview.

Want to read all 17 pages?

  • Fall '09

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture