PHAR2823 Lecture Notes - Lecture 2: Bioavailability, Solvation
Solids Advanced 2
17/8/18
Amorphous drug formulations:
High energy and thermodynamically unstable. Need to make sure it doesn’t convert back
to crystalline in transportation storage.
Solubility: low solubility often severely reduces the bioavailability of the drug and may lead to
pharmacologically effective molecules being abandoned. The transformation of a drug from
the crystalline state to a high-energy amorphous form generally leads to an increase in
solubility. BUT as the amorphous form per definition is a high energy state and therefore
metastable; need to stabilise amorphous drug formulations.
Current approaches to stabilise the amorphous form:
a) Surface coverage of amorphous particles
b) In situ formation of the amorphous form
c) Co-amorphous mixtures
Methods: ball mills, other production procedures, such as freeze drying, spray drying,
precipitation and hot melt processing.
What happens if molecules pack in a different way?
- Crystal form is ordering of atom/molecules for form crystal structure
- When the same chemical exists in different states we call it polymorphism
- Different properties like melting point and solubility. E.g. C, diamond or graphite.
Physical
properties
different in
different
polymorphs:
- Solubility
- MP
- Density
- Hardness
- Compres
sibility
Solvate/Hydrate
Solvation: the process of attraction/association of solvent molecules with a solute molecules or
ions
Hydration: disruption with water molecules not solvate molecules.
Document Summary
Need to make sure it doesn"t convert back to crystalline in transportation storage. Solubility: low solubility often severely reduces the bioavailability of the drug and may lead to pharmacologically effective molecules being abandoned. The transformation of a drug from the crystalline state to a high-energy amorphous form generally leads to an increase in solubility. But as the amorphous form per definition is a high energy state and therefore metastable; need to stabilise amorphous drug formulations. Current approaches to stabilise the amorphous form: surface coverage of amorphous particles, in situ formation of the amorphous form, co-amorphous mixtures. Methods: ball mills, other production procedures, such as freeze drying, spray drying, precipitation and hot melt processing. Crystal form is ordering of atom/molecules for form crystal structure. When the same chemical exists in different states we call it polymorphism. Different properties like melting point and solubility. Solvation: the process of attraction/association of solvent molecules with a solute molecules or ions.
