Powders and granulation

Question 1

Pharmaceutical definition of a powder

Answer 1

Describes a formulatin in which a drug powder has normally been mixed with other powdered exipients to produce the final product.

Question 2

what is dusting powder

Answer 2

powder mixes for external uses only
- dusting powder
- clotrimazole powder

powder mixes for internal use only
-oral powders
-oral antibiotic syrup (amoxicillin oral suspension)

Question 3

Measurments of powder flow properties

Answer 3

Angle of response

Bulk density

Critical orifice diameter

Question 4

Pharmaceutical granule definition

Answer 4

powder particles that have been aggregated to from a larger particle

Question 5

why do we granulate powders?

Answer 5

to prevent segregation
to improve the flow properties
to improve compaction properties

Question 6

Two granulation methods

Answer 6

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

Question 7

five primary bonding mechanisms

Answer 7

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

Question 8

Adhesive and cohesive forces

Answer 8

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)

Question 9

Interfacial forces in mobile liquid film

Answer 9

addition of increasing amounts of granulation fluid will produce a mobile liquid film around the particles

Question 10

solid bridges

Answer 10

solid bridges due to partial melting, hardening binders, crystallisation of dissolved substances play a part in sticking the pwoder particles together into granules

Question 11

attractive forces between solid particles

Answer 11

in the absence of a granulating fluid, 2 attractive forces operate:
-electrostatic
van der waals

Question 12

mechanical interlocking

Answer 12

particle size and shape will determine the degree of interlocking

Question 13

granulation equipment

Answer 13

shear granulator
-high-speed mixer/granulator
-fluidised-bed-granulator

Question 14

one common application of wet granulation

Answer 14

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

Question 15

extrusion / spheronisation

Answer 15

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

Question 16

advantages of pellets in the GI track

Answer 16

-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

Question 17

Advantages of pellets

Answer 17

-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

Question 18

Advantages of pellets

Answer 18

-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

Question 19

advantages of pellets in processing

Answer 19

-increased bulk density
-improved flow properties
- reduced dust production
-increased strength
-smooth surface for coating
regular shape for packing capsules

Question 20

disadvantages of pellets in processing

Answer 20

manufacture is more labour intensive than other granulation methods mainly due to the high levels of solvent required

Question 21

manufacturing process for pellets

Answer 21

1. dry blending of a single batch using normal powder mixing equipment
2. wet granulated
3. extrusion and forms a rod shaped particles uniform in diamter
   4.spheronised and forms spherical shaped particles
4. dried to achieve desired water content
   6.screened to achieve the desired narrow distribution

Question 22

factors effecting pellet quality

Answer 22

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