40 Questions
Why are solvates generally undesirable in pharmaceuticals?
Due to the presence of retained organic material
What is a co-crystal in the context of pharmaceuticals?
A crystal composed of two or more discrete chemical entities
What is a characteristic of pharmaceutical co-crystals?
The coformer is selected from the GRAS list of substances
What is a result of combining a drug molecule with a hydrogen-bonded coformer in a co-crystal?
An enhancement of the pharmaceutical properties of the drug
What is a characteristic of multicomponent crystalline forms?
They have a distinct identity and overlap with other forms
What is an amorphous solid?
A solid with no repeating long-range ordered arrangement of molecules
What is a reason why large molecular weight species may not form crystals?
Because they are too large and flexible
What is an example of an amorphous solid?
All of the above
What is the characteristic of crystalline solids in terms of their geometric shapes?
They have well-defined and often pleasing geometric shapes
What happens to the molecules in low molecular weight materials that undergo rapid solidification?
They don't have a chance to align in a crystal lattice
What is the process of formation of solid crystals from a homogeneous solution?
Crystallization
What is a characteristic of amorphous solids?
They do not have a melting point
What is the condition required for nucleation and crystal growth to occur?
Super-saturation state
What happens when the crystallization conditions are changed?
The molecules may form crystals with a different packing pattern
What is the temperature at which there is a major change in properties in amorphous solids?
Glass transition temperature
What is an example of a property that can be affected by a change in the packing arrangement of a molecule?
Melting point
What happens to amorphous solids when they are below their Tg?
They remain in a glassy state
What happens to amorphous solids when they are above their Tg?
They become rubbery
What is the term for the change in the packing arrangement of the same molecule, giving two different crystal forms?
Polymorphism
What is the effect of adding a plasticizer to an amorphous material?
It lowers the Tg
What is the type of polymorphism where only one polymorphic form is stable?
Monotropic polymorphism
Why do amorphous materials absorb more water vapour than crystalline materials?
Because they have a different molecular structure
What happens to the metastable polymorphic form in monotropic polymorphism?
It eventually converts to the stable form
What is an example of a plasticizer mentioned in the text?
Water vapour
What is the significance of polymorphism in drugs with low aqueous solubility?
It can have serious consequences for the bioavailability of the drug
What happens during the process of crystallization that can lead to the formation of hydrates?
Solvent molecules are trapped within the lattice
What is the term used to describe the difference in properties between hydrates and anhydrous forms?
Pseudopolymorphism
What is the typical effect of hydration on the dissolution rate of a drug?
It decreases the dissolution rate
What is the role of water in the lattice of a hydrate that has a slower dissolution rate?
It hydrogen bonds between drug molecules to tie the lattice together
What is the example of a drug that has a hydrate form with a slower dissolution rate?
Theophyline
What is the term used to describe a material that contains a solvent other than water in its lattice?
Solvate
What is the example of a solvate?
Ethanolate
What is enantropic polymorphism?
A type of polymorphism that can reversibly transform between alternative stable forms
Which polymorph has the highest dissolution rate?
The metastable form with the lowest melting point
What is the main issue with many drugs in terms of solubility?
They are hydrophobic and have very limited solubility in water
What is the difference between the stable α-polymorph and the metastable β-polymorph in terms of serum levels?
The stable α-polymorph produces lower serum levels, while the metastable β-polymorph produces higher serum levels
What is the risk associated with using the metastable form?
It will convert back to the stable form during the product's life, resulting in a change in properties
What is the correlation between the melting point of the different polymorphs and the rate of dissolution?
The polymorph with the lowest melting point has the highest dissolution rate
What is the main difference between monotropic polymorphism and enantropic polymorphism?
Monotropic polymorphism is irreversible, while enantropic polymorphism is reversible
What is the consequence of using the metastable form of a drug?
A change in the properties of the drug
Study Notes
Classification of Solids
- Crystalline solids have a regularly ordered, long-range, repeating pattern of constituent atoms or molecules in three spatial dimensions.
- Characteristics of crystalline solids:
- Exhibit well-defined and often pleasing geometric shapes.
- Have a melting point (temperature at which the crystal lattice breaks down).
Crystallization
- Crystallization is the process of formation of solid crystals from a homogeneous solution.
- Consists of two major events: nucleation and crystal growth.
- Requires the presence of super-saturation state.
Polymorphism
- If crystallization conditions are changed, molecules may form crystals with a different packing pattern.
- Results in different crystal forms with significant changes in properties.
- Example: melting point, dissolution rate, and milling and compaction (tableting) properties.
Types of Polymorphism
- Monotropic polymorphism: one polymorphic form is stable, and any other polymorph will eventually convert to the stable form.
- Enantropic polymorphism: reversible transformation between alternative stable forms under different conditions (temperature and pressure).
Polymorphism and Bioavailability
- Many drugs are hydrophobic and have limited solubility in water, resulting in low bioavailability.
- Example: chloramphenicol palmitate suspensions.
- Stable α-polymorph produces low serum levels, while metastable β-polymorph yields higher serum levels.
Hydrates
- Hydrates: materials that trap individual molecules of the solvent (often water) within the lattice.
- Examples: monohydrate, dihydrate, and trihydrate.
- Hydrates often have different properties from the anhydrous form.
Dissolution Rate of Hydrates
- Hydrates usually have a slower dissolution rate than the anhydrous form.
- Exception: hydrate form has a faster dissolution rate than the anhydrous form (e.g., erythromycin).
Solvates
- Solvates: materials that trap molecules of a solvent other than water within the lattice.
- Examples: ethanolate (ethanol).
- Undesirable in pharmaceuticals due to retained organic material being an impurity.
Co-crystals
- Co-crystals: homogeneous crystalline phase consisting of two or more discrete chemical entities bound together in the crystal lattice.
- Pharmaceutical co-crystals: combine pharmaceutical properties of the drug molecule with a hydrogen-bonded coformer in the crystal lattice.
Amorphous Solids
- Amorphous solids: molecules not packed in a repeating long-range ordered fashion.
- Formation:
- Large molecular weight species that are too large and flexible to align perfectly.
- Low molecular weight materials that undergo rapid solidification.
- Crystal formation followed by disruption (e.g., milling).
- Characteristics:
- No melting point.
- Glass transition temperature (Tg) marks a major change in properties.
- Below Tg, amorphous form is brittle (glassy state).
- Above Tg, amorphous form becomes rubbery.
- Plasticizers (e.g., water vapor) can lower the glass transition temperature.
This quiz covers the classification of solids, specifically crystalline solids, their structure, characteristics, and crystallization process.
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