Powders and granulation Flashcards
Pharmaceutical definition of a powder
Describes a formulatin in which a drug powder has normally been mixed with other powdered exipients to produce the final product.
what is dusting powder
powder mixes for external uses only
- dusting powder
- clotrimazole powder
powder mixes for internal use only
-oral powders
-oral antibiotic syrup (amoxicillin oral suspension)
Measurments of powder flow properties
Angle of response
Bulk density
Critical orifice diameter
Pharmaceutical granule definition
powder particles that have been aggregated to from a larger particle
why do we granulate powders?
to prevent segregation
to improve the flow properties
to improve compaction properties
Two granulation methods
Dry granulation
-powders are miexed and compressed to form a slug
-slugs are then milled and sieved.
-used when APIs do not compress well after wet granulation or are sensitive to granulation fluids (water)
Wet granulation
-powders are dry blended and a granulating fluid is added.
-wet granules are screened, sieved and dried
five primary bonding mechanisms
NEED AULTONS FOR MORE DETAIL
1. adhesive and cohesive forces in the immobile liquid film
2. interfacial forces in the mobile liquid film within granules.
3. solid bridges after solvent evaporation
4. attractive forces (adhesive and cohesive) between solid particles
5. mechanical interlocking
Adhesive and cohesive forces
the presence of a sufficient amount of liquid in a powder will result in a very thin, immobile layer (adhesive forces)
Interparticular distances will be reduced causing increased particle attraction due to van der waals (cohesive)
Interfacial forces in mobile liquid film
addition of increasing amounts of granulation fluid will produce a mobile liquid film around the particles
solid bridges
solid bridges due to partial melting, hardening binders, crystallisation of dissolved substances play a part in sticking the pwoder particles together into granules
attractive forces between solid particles
in the absence of a granulating fluid, 2 attractive forces operate:
-electrostatic
van der waals
mechanical interlocking
particle size and shape will determine the degree of interlocking
granulation equipment
shear granulator
-high-speed mixer/granulator
-fluidised-bed-granulator
one common application of wet granulation
Multiparticulates (pellets/beads)
-small size 0.7 - 2.0mm
- good flow properties
- narrow particle size distribuiton
-low friability reduces dust formation
-distributed throughout GI track
-high surface area / volume ratio ideal for coating and maximises dissolution
extrusion / spheronisation
wet granulation is not immidietly dried until it has been shaked into sphetirical form by extradating them and then spheronisation they are then dried and sphere coated, the converted into capsules or tablets
advantages of pellets in the GI track
-less irregular passage through the GI track than single unit dosage forms
-less chance of ulcerative damage often experienced with single unit dosage forms
-failure of individual pellets will not result in dose dumping
-can contain high levels of active ingridient without using excessively large particles
Advantages of pellets
-immidiete release or controlled release possible
- can be filled into hard gelatine capsules or compacted into tablets to form unit dosage forms
-can contain two or more active ingridiens
incompatible actives can be manufactured as seperate pellets
-can be coated at different ‘coat weights’ to produce
Advantages of pellets
-immidiete release or controlled release possible
- can be filled into hard gelatine capsules or compacted into tablets to form unit dosage forms
-can contain two or more active ingridiens
incompatible actives can be manufactured as seperate pellets
-can be coated at different ‘coat weights’ to produce a range of release rates
advantages of pellets in processing
-increased bulk density
-improved flow properties
- reduced dust production
-increased strength
-smooth surface for coating
regular shape for packing capsules
disadvantages of pellets in processing
manufacture is more labour intensive than other granulation methods mainly due to the high levels of solvent required
manufacturing process for pellets
- dry blending of a single batch using normal powder mixing equipment
- wet granulated
- extrusion and forms a rod shaped particles uniform in diamter
4.spheronised and forms spherical shaped particles - dried to achieve desired water content
6.screened to achieve the desired narrow distribution
factors effecting pellet quality
water content
-if less than the lower limit lots of dust formed furing spheronisation, producing a large yield of fines
-if more then over wetted mass results in agglomeration of individual pellets (large sphere)
composition
- different grades of the same exipient
-solubility of exipients and drug
-particle size of starting materials
-amount of type of granulation fluid used
