XRPD Quantification of Crystalline and Amorphous Ratio
Determination of crystallinity for APIs and excipients
Overview
Since the physico-chemical properties of pharmaceuticals are influenced by their solid-state forms, the crystallinity of an active ingredient has a profound impact on both processing behavior (compressibility, compactibility and hygroscopicity) and the bioavailability of the active ingredient in the finished product.
Due to its better stability, the desired solid-state form for an active pharmaceutical ingredient (API) is usually crystalline. However, the amorphous state is sometimes required to achieve sufficient efficacy for low soluble active ingredients.
During the production or processing of pharmaceutical solids, certain procedures such as milling, spray drying or lyophilization can disrupt the crystalline structure and lead to the formation of amorphous regions. On the other hand, undesirable recrystallization can take place within amorphous formulations, driven by thermodynamic or physico-chemical factors.
To establish the integrity of the finished product it is important to be able to determine the existence and amount of amorphous material within a crystalline matrix or crystalline material in an amorphous matrix. XRPD is successfully used for the determination of crystallinity, both for small crystalline contents in an amorphous matrix and vice versa. An approximate LOQ of 1% wt is achievable for the quantification of crystalline material in amorphous matrices.
Related Application Note
XRPD Quantification of Crystalline Forms in Amorphous API →
Conference Poster
Download Poster: Crystallinity Determination by XRD, NIRS, DSC (PDF)
Work performed in cooperation with industrial partner.