Lecture 03- Solid-State Properties

What is the smallest unit of a chemical compound that retains its properties?

Molecule

What are particles made of?

Aggregated molecules

What are the three states of matter?

Solid, liquid, gas

What state are most drugs and excipients at room temperature?

Solid

What holds drug molecules close together in solid particles?

Intermolecular forces

What are the two major solid-state forms of drugs?

Crystalline and amorphous

How are molecules arranged in a crystalline solid?

Defined order

What structure makes up a crystal?

Lattice of unit cells

How are molecules arranged in an amorphous solid?

No orderly arrangement

Do crystalline drugs have a distinct melting point?

Yes

What happens to the crystal lattice at the melting point?

Lattice breaks down

Do amorphous drugs have a distinct crystal lattice?

No

Do amorphous drugs melt at one specific temperature?

No, over a range

Which has greater water solubility: crystalline or amorphous?

Amorphous

Which has faster dissolution: crystalline or amorphous?

Amorphous

Which has better stability: crystalline or amorphous?

Crystalline

Which has a stronger lattice: crystalline or amorphous?

Crystalline

Which form generally has a higher melting point?

Crystalline

Which form is easier to remove molecules from?

Amorphous

What are different crystalline forms of the same drug called?

Polymorphs

What is the ability to form multiple crystal arrangements called?

Polymorphism

Can polymorphs have different physicochemical properties?

Yes

What determines which polymorph is most stable?

Conditions

What is the most thermodynamically stable polymorph called?

Ground state

What is a less thermodynamically stable polymorph called?

Metastable state

Which polymorph has the stronger lattice?

Ground state

Which polymorph has the higher melting point?

Ground state

Which polymorph has better water solubility?

Metastable

Which polymorph dissolves faster?

Metastable

Which polymorph has better stability?

Ground state

Can metastable polymorphs convert to the ground state?

Yes

Can polymorph conversion affect shelf life?

Yes

How long can metastable-to-ground-state conversion take?

Weeks to years

What is the most stable polymorph of cocoa butter?

Beta crystal

What metastable cocoa butter polymorph forms after rapid cooling?

Alpha crystal

What can the alpha cocoa butter crystal eventually convert into?

Beta crystal

What are crystals containing solvent molecules called?

Solvates

What are solvates also called?

Pseudopolymorphs

What is a solvate containing water called?

Hydrate

What percentage of drugs form hydrates?

About 30%

What does monohydrate mean?

One water molecule

What does trihydrate mean?

Three water molecules

What does heptahydrate mean?

Seven water molecules

Can hydrates have different physical properties from anhydrous drugs?

Yes

Which usually has better solubility: anhydrous or hydrate?

Anhydrous

Which usually dissolves faster: anhydrous or hydrate?

Anhydrous

Why can hydrates have stronger lattices?

Hydrogen bonding

When substituting a hydrate for an anhydrous drug, what must be recalculated?

Amount weighed

Why must more hydrate sometimes be weighed?

Contains water

Which solid form is preferred when rapid dissolution is needed?

Amorphous

Which polymorph is preferred for most pharmaceutical applications?

Ground state

When might a metastable form be preferred?

Improved solubility

What are powders?

Drug/excipient particles

What powder property describes absorbing atmospheric water?

Hygroscopic

What type of powder absorbs enough moisture to form a solution?

Deliquescent

How should hygroscopic and deliquescent powders be stored?

Tight containers

What can be added to protect powders from moisture?

Desiccants

What happens to improperly stored hygroscopic powder weight?

Increases

What is loss of water from a drug hydrate called?

Efflorescence

What can efflorescence make a powder become?

Damp or pasty

What is a mixture that melts below the melting points of its individual components?

Eutectic mixture

What can happen when eutectic powders are mixed at room temperature?

They may melt

What are particles in the micrometer range called?

Micronized particles

What is the process of reducing particle size called?

Comminution

What manufacturing process reduces particle size?

Milling

What is used to sort particles by size?

Sieves

What is particle-size reduction by grinding in a mortar and pestle?

Trituration

What is particle-size reduction using a small amount of liquid?

Levigation

Should the drug be soluble in the levigating liquid?

No

What are common levigating liquids?

Mineral oil or glycerin

What is the main goal of particle-size reduction?

Improve uniformity

What is the relationship between particle size and surface area?

Inverse

What happens to surface area when particle size decreases?

Increases

What usually happens to dissolution rate when particle size decreases?

Increases

What is wettability?

Solid-liquid contact

Is wettability the same as solubility?

No

What measures the wettability of a solid?

Contact angle

Does a smaller contact angle indicate better or worse wetting?

Better wetting

What contact angle represents complete wetting?

0 degrees

Can micronized powders have poor wettability?

Yes

What can poor wettability cause particles to do?

Aggregate

What can aggregation result in?

Clumping

What can poor wettability limit?

Dissolution and absorption

What can improve poor wettability?

Wetting agents

Why is powder flow important?

Uniform dosage forms

What happens to attractive forces as particle size decreases?

Increase

What can increased particle attraction do to powder flow?

Decrease flow

What particle shape generally improves powder flow?

Spherical

What excipients improve powder flow?

Flow enhancers

What is an example of a glidant?

Talc

What process forms larger spherical granules to improve flow?

Granulation

What is the goal of powder mixing?

Random mix

What are the three mechanisms of powder mixing?

Convective, shear, diffusive

What is movement of large groups of particles called?

Convective mixing

What is movement of one powder layer over another called?

Shear mixing

What is random movement of individual powder particles called?

Diffusive mixing

What is commonly used for powder mixing during compounding?

Mortar and pestle