Pharmaceutical solids can exist in different physical forms, which may possess different chemical and physical properties including
- melting point
- interfacial and
- mechanical properties
In turn, these properties can have a direct impact on important pharmaceutical aspects such as,
- drug substance processability and
- drug product manufactureability
A few examples
The solid state properties (physical form and particle size) are critical for the increasing number of BCS Class II (and class IV) small pharmaceutical molecules under development has it as direct impact on the bioavailability.
BCS = Biopharmaceutics Classification System
Class I – High permeability and high solubility
Class II – High permeability and low solubility
Class III – Low permeability and high solubility
Class IV – Low permeability and low solubility
Unexpected appearance or disappearance of a form during the production may lead to serious consequences in from of costly delays, as in the case of the appearance of a new polymorph of ritonavir in mid-1998.
The glass transition temperature and the molecular mobility are the principal predictors of stability of amorphous material i.e. solid biopharmaceuticals.