Medchem Unit 9 Lect 7&8

What is micromeritics?

The science and technology of small particles

Why are small particle properties important?

They determine how particles interact with the environment and form dosage forms

What is the starting form of most pharmaceutical products?

Solid form (powders, granules, crystals)

Why is particle size important?

It affects dosage form, drug delivery, and therapeutic effect

What are pharmaceutical particles?

Usually powders but can also be globules (liquids) or gases

What roles can particles have?

Dosage form, component of dosage form, API, or excipient

What are common powder mixing methods (small scale)?

Trituration, rolling/tumbling, sifting, spatulation

What is geometric dilution?

Mixing starting with smallest quantity and doubling amounts with each addition

What properties are affected by particle size?

Solubility, porosity, flow, texture, stability, content uniformity, sedimentation rate

What is micronization?

Reduction of particle size to micron dimensions to improve bioavailability

Example of micronization benefit?

Griseofulvin shows increased absorption and allows lower dose

Why is particle size critical in drug absorption pathway?

It affects disintegration → dissolution → absorption → bioavailability

What is particle morphology?

Shape and structure of particles

Examples of particle shapes?

Spherical, ellipsoid, plates, rods, needles, cubes

What is polymorphism?

Presence of multiple crystalline forms

Why is morphology important?

It affects surface area, absorption, and bioavailability

What is equivalent spherical diameter?

Diameter of a sphere with same property (surface area, volume, etc.) as irregular particle

Types of equivalent diameters?

Surface diameter

Volume diameter

Stokes' diameter

Projected area diameter

Aerodynamic diameter

Key parameters for particles?

Individual → shape, surface area

Powder → size range, number/weight of particles

What is particle size distribution?

Range of particle sizes and fraction of particles in each range

What is monodisperse?

Same size and shape particles

What is polydisperse?

Wide range of sizes and shapes

What is a frequency distribution curve?

Graph of number/weight of particles vs size range

What is the key principle of particle size?

Particle size → solubility → dissolution → absorption → bioavailability

How does decreasing particle size affect surface area?

Increases surface area

How does increased surface area affect solubility?

Increases solubility

What does the Noyes-Whitney equation describe?

Dissolution rate is proportional to surface area

What does increased surface area do to dissolution?

Increases dissolution rate

Why is dissolution important?

Only dissolved drug can be absorbed

What is rate-limiting step?

When dissolution is slower than absorption

What is the key concept of particle size and dissolution?

Smaller particle → greater surface area → better dissolution

How does particle size affect bioavailability?

Smaller particles → higher dissolution → better bioavailability

What is porosity?

Measure of void space in powder

What creates pores?

Cracks, cavities, holes from processing

What is bulk volume?

Volume occupied without compression

What is tapped volume?

Volume after compaction

What is bulk density?

Mass / bulk volume

What is tapped density?

Mass / tapped volume

What is true density?

Excludes pores and spaces

What is envelope density?

Includes pores but not interparticle spaces

How does porosity affect dissolution?

Pore size distribution influences dissolution rate

What is angle of repose?

Steepest angle before powder slides

What does angle of repose indicate?

Flow properties of powder

Low angle of repose indicates?

Good flow

High angle of repose indicates?

Poor flow

How does particle size affect topical preparations?

Smaller particles → smoother, non-gritty texture

What is particle size requirement for ophthalmic preparations?

< 10 µm

Why?

Prevent irritation and improve retention

What is particle size requirement for parenteral formulations?

< 10 µm

Why?

Prevent embolism and toxicity

What is agglomeration?

Particles cluster together

What are particle size measurement methods?

Microscopy, sieving, sedimentation, Coulter counter, dynamic light scattering, laser diffraction

What is microscopy?

Direct measurement of particles individually

Resolution ranges?

Light: 0.2-100 µm

UV

0.1 µm

Electron

0.001-0.2 µm

What is sieving?

Separation based on mesh size and weight fractions

Lower size limit?

~43 µm (woven mesh), ~5 µm (electroformed)

Key rule of mesh size?

Larger mesh number = smaller particle size

USP powder classifications?

Very coarse >1000 µm

Coarse 355-1000 µm

Moderately fine 180-355 µm

Fine 125-180 µm

Very fine 90-125 µm

What is sedimentation method?

Measures particle size based on settling velocity

What law is used?

Stokes' Law

What is Coulter counter?

Measures particle size based on change in electrical current

What is laser diffraction?

Determines size based on light scattering angles

What is comminution?

Reduction of particle size

What are types of comminution?

Mechanical and manual

What forces reduce particle size?

Attrition, rolling, impact

What is a roller mill?

Uses compression and shear (rolling + attrition)

What is a hammer mill?

Uses impact force

What is an attrition mill?

Uses rubbing between surfaces

What is trituration?

Grinding powder in mortar and pestle

What is levigation?

Particle reduction using liquid and grinding

Examples of levigating agents?

Mineral oil, glycerin, propylene glycol

What is pulverization by intervention?

Dissolve then recrystallize to form smaller particles

What is an ointment mill?

Mechanical device to reduce particle size in semisolids

What is an electronic mortar and pestle?

Mixing device (not primarily for size reduction)

Why is particle size important?

Affects drug delivery, dissolution, absorption, and formulation properties

What methods are used?

Direct and indirect measurement methods

What techniques reduce particle size?

Manual and mechanical methods