Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

Drug dissolution is influenced by polymorphism, which refers to the existence of a drug substance in multiple crystalline forms like polymorphs, solvates, and amorphous forms.

A drug's polymorphs share the same chemical formula but different chemical structures, and so they exhibit different physical properties.

For instance, chloramphenicol suspension has multiple crystal forms. However, a higher percentage of highly soluble β-polymorph enhances drug absorption.

Metastable polymorphs can convert to a more stable form during manufacturing and can cause issues like tablet cracking or preventing granulation compression.

During the manufacturing process, some drugs interact with solvents to form solvates. Different crystal forms of these solvates are referred to as pseudopolymorphs.

When the solvent is water, hydrates are formed. In the case of erythromycin hydrates, the plot of percent dissolved versus time displays different solubility patterns for dihydrate, monohydrate and anhydrate forms.

Lastly, amorphous forms lack crystalline structures and dissolve more rapidly in aqueous solutions than crystals.