Study of dabigatran etexilate polymorphs for improved manufacturing processability

Abstract

In the present work on anhydrous form-I and tetrahydrate form of Dabigatran etexilate a comparative study was done to seek a polymorph which will perform better in downstream processing and dissolution. Anhydrous form I of Dabigatran etexilate used in this study is having a needle shape. Tetrahydrate form was recrystallized from the anhydrous form I by solvent recrystallization using a slow evaporation method with acetone at NMT 25 °C, 2–8 °C, and −20 °C. The crystal shape of recrystallized tetrahydrate form was tabular. Scanning electron microscopy (SEM) was used to confirm the shape of crystals. Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), and Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed polymorphic change. Flow characterization indicates that tetrahydrate has better bulk density, tapped density, Hausner ratio, and Cars index than anhydrous form I. Kawakita analysis shows that tetrahydrate has better compactibility and lesser cohesive nature than anhydrous form I. Heckel plots indicates tendency of tetrahydrate form to undergo plastic deformation linearly as pressure increases compared to anhydrous form I. The tensile strength of tetrahydrate is better than anhydrous form I and it also have a lesser tendency for capping and lamination at higher compression pressure. A dissolution study in USP dissolution media for dabigatran etexilate showed that tetrahydrate has a higher dissolution rate than anhydrous form I which is also backed by higher solubility. Overall, the tetrahydrate form can be preferred over the anhydrous form I during polymorph selection.