Question

Describe two techniques that can be used to identify polymorph forms of a drug substance. When should a less stable polymorphic form of a drug substance be used? What is the effect of using a less stable polymorph on shelf-life and explain your reasoning.

Clear , detailed answer required please

Answer 1

Polymorphism is defined as the ability of a solid material to exist in two or more crystalline forms with different arrangements or conformations in the crystal lattice. they have different physicochemical properties such as solubility, dissolution rate stability, and bioavailability. More than 50 % od the APIs active pharmaceutical ingredients are estimated to have more than one polymorphic form.

Various techniques have been used to identify the polymorphic form of a compound such as:

1. Scanning electron microscope (SEM): scans the surface of a material with a focussed beam of electrons to produce an image of the sample. It determines the topography and type of crystals.

2. FTIR and RAMAN spectra: are used to identify the polymorphism of a compound. Other than this PXRD, Single crystal XRD are also established techniques used to identify polymorphism.

Sometimes the metastable form formed is more soluble than the corresponding stable polymorphic form so when it comes to better bioavailability and dissolution less stable polymorphic form can be used but they transform more readily to the most thermodynamically stable form in a short time which affects the shelf life of a drug.