Lecture 3: preformulation considerations 2 Flashcards
What is the characteristic of the arrangement of molecules in a crsytalline structure?
The molecules are packed in a defined order, and this order repeats over and over again throughout the solid structure.
What is a unit cell?
The unit cell is the smallest unit of volume that contains all of the structural and symmetry information of the lattice.
Why does temperature remain constant during a phase change?
Because the heat energy produced is used up in changing the state of matter and also for breaking numerous bonds or attractive forces.
True or false?
For a pure crystalline material, the melting point is always equal to the freezing point.
True
What are some ways to decrease the solubility of a drug in a solvent?
- Solvent evaporation
- Cooling
- Addition of an anti solvent which the drug has a low solubility in
What are the 2 steps for crystallisation?
- Nucleation: formation of a small mass onto which the crystal can grow
- Growth
Why is nucleation a slow process?
Because the initial crystal components must impinge on each other in the correct orientation and have placement for them to adhere
How do you provide nucleation sites for crytallisation?
- Scratching the container
- Dip foreign materials like strings into the container
What are crystal habits?
- Crystal habit refers to the external shape of the crystal
- It is a consequence of the rate at which different faces of the crystal grow.
True or false?
The same compound can crystallize to form different shapes in different solvents.
True
What are some crystallographic defects?
- Interstitial atom
- Vacancy
- Substitutional smaller/larger atom
- Frankel-pair
Why does fast solvent evaporation introduce more crystal defects?
Fast solvent evaporation forces the atoms to form the structure very quickly, and so there isn’t enough time for them to arrange themselves properly.
What are some processes that can cause defects to crystals?
- Rapid recrystallisation from solution
- Freeze drying (it produces amorphous materials)
- Incorporation of impurities
- Mechanical stress like milling and griding and compression
How does the melting point of a crystal change after more defects are introduced, and why?
- The melting point decreases
- Impurities change the intermolecular forces of the crystal structure and make it less stable, so less energy is required to break down the crystal lattice
What is polymorphism?
The ability of a substance to exist as two or more crystalline phases, with different arrangement of the molecules and/or different conformations of the molecules.
Given that a crystalline drug exhibits two polymorphs I and II, if we bring both crystals to a liquid/vapor state by heating, are they identical?
Yes.
What properties may differ between polymorphs?
Melting point
Solubility
Mechanical strength
Color
What are some characteristics of amorphous structures?
- Liquid that has lost its ability to flow
- No long range order
- No sharp melting point
- Higher free energy, solubility and chemical reactivity compared to their crystalline counterparts
What is glass transition temperature (Tg) ?
The temperature at which an amorphous solid changes from a glassy state to a rubbery state or vice versa
Do crystalline and amorphous forms both have a glass transition temperature?
No, only amorphous forms do.
Why is it dangerous for the Tg of a drug to be low?
This means that the state of the drug will keep changing from glass to rubbery
Is Tg lower or higher than melting point?
Lower
(The glass state becomes rubbery before it becomes liquid)
Are amorphous forms better or worse at absorbing water than crystalline forms?
Better, because water can pass through the bulk region
What are the different methods to produce amorphous forms?
- Vapor condensation
- Shock, irradiation, or intense grinding of crystals
- Solid-state diffusion controlled reaction
- Supercooling of the melted form
- Precipitation from solution or solvent evaporation
- Compaction of crystals
What are the ways by which amorphous solids can be characterized?
- Powder X-Ray Diffraction (PXRD)
- Differential scanning calorimetry (DSC)
What is Powder X-Ray Diffraction (PXRD)?
It’s a non destructive technique that can yield the unique fingerprint of Bragg reflections associated with a crystal structure.
What is the difference in the fingerprint of crystalline and amorphous solids in PXRD?
- The PXRD of crystalline solids yields nice sharp peaks
- The PXRD of amorphous solids doesn’t have sharp peaks and it has much broader peaks
pls revise dsc
pls revise dsc
