Pharmaceutical Co-crystals

Question 1

What is a co-crystal?

Answer 1

Crystalline material composed of two or more diff molecules, one of which is the API, in a defined stiochiometric ratio within the same crystal lattice that are associated by non ionic and non covalent bonds

Question 2

What is a coformer?

Answer 2

A component that interacts nonionically with the API in the crystal lattice that is not a solvent and is typically non-volatile

Question 3

What is a polymorph?

Answer 3

Different crystalline forms of the same API

This may include solvation and hydration products and amorphous forms

Diff polymorphic forms are considered the same APIs as per regulatory scheme

Question 4

What are salts?

Answer 4

Any of numerous compounds that result from replacement of part or all of the acid hydrogen of an acid with a metal or a radical acting like a metal: an ionic or electro alert crystalline compound

Diff salt forms of the same active moiety are considered diff APIs as per regulatory scheme

Question 5

What interactions are involved in the formation of pharmaceutical co-crystals?

Answer 5

1. H2 bonds
2. Pi-pi stacking supramolecular interactions
3. VDW
4. Halogen bonding

Question 6

What are supramolecular synthons?

Answer 6

Spatial arrangements of intermolecular interactions which occur frequently within crystal structures

Question 7

What is a homo-synthon?

Answer 7

Formed between the same fucntional group of one chemical component

Question 8

What is a homo-synthon?

Answer 8

Formed between same of diff functional groups of two or more chemical components

Question 9

The non API components should be…

Answer 9

Non toxic with no adverse effects.

Ideally the co-crystal coformer should be part of the USA FDA “everything added to food in the US” list which comprises 3000 substances that are suitable as food additives or approved as generally regarded as safe.

Question 10

What are methods of co-crystalisastion?

Answer 10

1. Cooling crystalisation
2. Solvent evaporation
3. Freeze drying
4. Spray drying
5. Grinding
6. Spherical crystalisation
7. Sublimation
8. Anti solvent method
9. Vapour diffusion
10. Sonic crystalisation

Question 11

What is mechanichemistry?

Answer 11

A field that deals with athermal or ultra fast chemical reactions between solids and surrounding gaseous or liquid molecules under mechanical forces.

Method of synthesising co-crystals

Question 12

What are the roles of co-crystals?

Answer 12

1. Enchance solubility
2. Improve physical stability
3. Modify mechanical properties
4. Combined therapeutic effects

Question 13

What are commercially available co-crystals?

Answer 13

1. Depakote —> Valproic acid — [valproate sodium] epilepsy
2. Entresto —> [valsartan sodium]—[sacubutril sodium] heart failure