Title:X-ray Powder Diffraction Spectroscopy as a Robust Tool in Early Predicting Bioavailability of Pharmaceutical Formulation Containing Polymorphic Drug Substance
VOLUME: 10 ISSUE: 3
Author(s):Abhishesh K. Mehata*, Deepa Dehari, Senthil R. Ayyannan and Madaswamy S. Muthu
Affiliation:Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, 221005
Keywords:Amorphous, bioavailability, dissolution, solid dispersion, polymorphism, X-ray powder diffraction.
Abstract:X-ray powder diffraction (XRPD) is a unique, solid-state analytical tool used to study the
3D structure of small or macromolecules by their x-ray diffraction or scattering patterns. X-ray diffraction
by a crystal reflects the periodicity of crystal architecture; any imperfections within the crystal architecture
can be easily identified by its poor diffraction pattern. Recently, an open crystallography database
reported that more than 85 % of drug compounds are crystalline and exist in different polymorphic
states. Physicochemical properties of pharmaceutical drug products composed of active pharmaceutical
ingredients (APIs) and excipients are interdependent on the physical state and forms in which
APIs are distributed in excipients that determine the in-vivo and ex-vivo performance of the product.
Amorphous APIs have relatively higher dissolution and bioavailability than crystalline form but with
lower phase stability. During the formulation development and storage phase, the conversion is higher
that largely impacts the bioavailability of the drug product. In this manuscript, we have presented the
case study of itraconazole and apigenin; both are crystalline APIs, that, with the help of solid dispersion
technology, are converted into amorphous drug products with enhanced oral bioavailability. The realtime
monitoring of the physical form of API in the formulation was possible with the help of XRPD
and other supporting data obtained from differential scanning calorimeter (DSC), which can be correlated
with the dissolution and in-vivo performance of the formulation.
