Crystallography - WIP Flashcards
What is a supramolecular Synthon?
During crystallisation of an organic solid, patterns of intermolecular interactions are established. Analysis of crystal structure reveals that some patterns are frequently encountered called “supramolecular synthons”
Supramolecular synthons can be used to design a supramolecular synthesis, the products being cocrystals
What different properties can Polymorphs have?
Physico-chemical – melting point, stability/reactivity, solubility, density, vapour pressure
Mechanical – hardness, particle flow, tabletting, compactability
Spectroscopic – UV/visible colour, IR and Raman, solid-state NMR
Pharmaceutically related – bioavailability, formulation properties, interactions with excipients in tablet
How can you grow metastable Polymorphs?
Nuclei of less stable polymorphs that would normally dissolve can keep growing in high supersaturation (dissolved above equilibrium solubility, the solution dries to form crystals to reach equilibrium again) regimes. This grows multiple forms, not just the most stable.
Polymorph example - Paracetamol
Has 2 well-established polymorphs, form 1 is easily obtained but does not compress well, form 2 will form tablets but not easy to obtain from solution. However as form 2 is not stable and does not appear during normal large-scale crystallisation, commercial products are made of form 1 with lots of binding material.
Polymorph example - Ritonavir
Ritonavir form 1 is a beta sheet, form 2 is a molecular stack which is not bioavailable
The new form occurred and was unable to be removed or prevented. The cause was the change of conformation (cis/trans), causing different solubility properties
crystal screening?
What is the Biopharmaceutics Classification System (BCS)?
Solubility and permeability relationship - solid state formulations relate to solubility and dissolution rates
Class I - High solubility, High permeability
Class II - Low solubility, High permeability
Class III - High solubility, Low permeability
Class IV - Low solubility, Low permeability
What is a Pharmaceutical Cocrystal?
Pharmaceutical cocrystals - When at least one component is therapeutically active, and the others are pharmaceutically acceptable
Design solubility for co-crystals refers to the process of tailoring or engineering the solubility properties of a co-crystal system in order to achieve a desired dissolution rate, bioavailability, or therapeutic efficacy
