Solid State Flashcards
From gas to solid
Decreasing intermolecular distance
Decrease in molecular mobility
Decrease in potential energy
Impact of solid state properties
• Physicochemical properties – Solubility – Dissolution rate – Bioavailability – Stability (physical and chemical) – Melting point – Surface activity – Density – Electrostatic, mechanical and optical properties – Formulation design
Solid ->
AMORPHOUS or CRYSTALLINE
Crystalline ->
POLYMORPHS
CO-CRYSTALS
SOLVATES, HYDRATES
Crystalline state
- Molecules arranged in orderly defined manner with same repeating units
- Lower potential energy than amorphous state
- Repeating units can be arranged differently within the crystalline form of the same substance
Methods of crystallisation
• Supersaturated solution • Crystallisation through cooling molten sample below its melting point – Suppositories – Creams – Gels • Precipitation of solids in solutions – Evaporation of liquid – Addition of anti-solvent – After solubility of sample changed by temp/pressure/pH of the system
Crystallisation process
• Nucleation
Crystallisation process
– First step in forming crystals
– A small mass (solute molecules) cluster together to form a ‘nuclei’ on which a crystal can grow
• Growth
– The continued growth of the nuclei
• In order to achieve nucleation and growth the solution must be supersaturated (when no more powder or solid will dissolve)
Polymorphism
• When a crystalline state solid possesses: – Different crystalline forms
– Different packing pattern
– Different lattice energies
– Different properties
These can present in:
– A stable form: higher MP, slower dissolution rate
– Metastable form: lower MP, faster dissolution, increase in apparent solubility
Polymorphism (2)
• The metastable form will transform into the most stable form
– Can be slow/quick
– Conversion rate dependant on:
• Energy difference of metastable and stable forms
• Environmental conditions
• Monitoring storage conditions and shelf life of polymorphs important
• Example: Paracetamol is a high dosage drug with poor compression properties. Large studies have been carried out to find another polymorph with a more desirable nature
• Monotropic polymorphism:
Only one stable polymorphic form (metastable will convert into stable over time)
• Enantropic polymorphism:
Material reversibly transformed between alternative stable forms. Less common.
Hydrates and solvates
• During crystallisation the solvent molecules can be trapped in the crystal lattice
• Hydrate
– Solvent is water
• Solvate
– Another solvent instead of water eg. Organic solvents such as ethanol
Hydrate vs. anhydrous form
• Different properties
• ‘Pseudopolymorphism’–used to describe the difference between hydrates and anhydrous forms
• The hydrated form could have a slower dissolution rate
– Water helps to strengthen the lattice E.g. Theophylline
• The hydrated form could have a faster dissolution rate
– Water weakens the lattice E.g. Erythromycin
Amorphous state
• Lower packing efficiency (less ordered)
• Greater intermolecular distance
• Greater molecular mobility
– Stronger chemical reactivity
– Faster chemical degradation rate
– Higher physical instability
– May convert to thermodynamically more stable crystalline form over time
• Often higher solubility
– Potential to enhance solubility and bioavailability of a poorly water soluble drug
Why are solids amorphous?
– Insufficient solidification time for molecules to form order
– Lack of kinetic energy to overcome barrier between crystal-liquid interface
– The crystalline process has been broken through processing
• E.g. milling (but may still revert back to crystalline depending on energy required)
