Question

1- Particle size reduction and granulation are both applied to formulate micronised drug particles and drug granules respectively as final dosage forms. Giving one pharmaceutical formulation for each, discuss the reasons for each process and the characteristics for the final dosage form selected.

2- Using paracetamol as your example, explain THREE reasons why different formulations of the same drug might be desirable for administration through different routes. Your answer should describe the pathway of drug absorption to elimination for each route.

Answer 1

1)Micronization:

Size reduction is performed for many pharmaceutical applications. Micronization means that, the particle size of a drug is generally less than 50 microns.

Reasons for size reduction via micronization:

-easy handling

-increase in surface area per unit volume:smaller particles have higher solubility and dissolution rates due to the larger surface area to volume ratio and, therefore, a better chance for faster absorption

-faster onset of action

Example of formulation:Suspensions containing microparticles

-Uniform appearance

-Enhanced solubility and dissolution rate which helps in fast absorption and fast onset of action of the drug

-Micronization allows the suspensions to be developed without the use of surfactants, which is sometimes advantageous in reducing the undesired effects of some excipients

Granulation:

Granulation is the process of agglomeration of fine particles into larger granules, typically of size range between 0.2 and 4.0 mm .

Reasons for granulation:

-improved bulk density and flow properties (Many powders, due to their small size, irregular shape or surface characteristics, are cohesive and do not flow well. Granulation produces larger and more isodiametric particles that increases flow property)

-prevention of the problems of caking, segregation, and poor tableting performance in the downstream processing(Normally, while manufacture,the smaller and/or denser particles concentrates at the base of the container with the larger and/or less dense ones on the top. Granulation helps in preventing this)

-reduced dustiness of the fine particles

-improved material dispersion

-increased porosity to maximize dissolution rate

Example of formulation:Tablets produced by granulation

-good appearance,without particle segragation

-easily compactable

-better content uniformity

-improved cohesive strength,prevents easy breakage.