Study of Different Crystal Habits of Aprepitant: Dissolution and Material Attributes

Satyajit R Datir,Samarth D Thakore,Pradeep Kumar,Arvind Kumar Bansal,Sanyog Jain,Mrudula H Bele,Bhargavi Nallamothu,Dinesh Kumar

doi:10.3390/app11125604

Abstract

In the present study, aprepitant (APT) was selected to find its suitable crystal habit, which can improve its existing poor dissolution and manufacturing processability. Solvents were screened out for solubility analysis of APT and further crystal habit modification. Solid-state characterization studies like powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier infrared spectroscopy (FTIR) distinguished that tabular crystal habit was generated from acetone (APT-AC) and long tabular crystal habit was generated from ethyl acetate (APT-EA). Kawakita analysis and powder flow property studies showed that APT-EA is cohesive, has poor flow property and low bulk density compared to APT-AC (p < 0.05). Heckel plots reflected that APT-EA shows higher fragmentation and particle rearrangement during the initial stages as indicated by the higher intercept values. Higher slopes in APT-EA and APT-AC confirmed better plasticity but lower yield pressure in APT-AC proved good plastic deformation compared to APT-EA (p < 0.05). The dissolution profile of the APT-EA was found to be better than that of APT-AC. Overall, it can be concluded that APT-AC crystal habit has a better flow rate, tensile strength, and plasticity whereas APT-EA has better dissolution.

Highlights

Polymorphism is the ability of a molecule to pack in different crystal lattices whereas crystal habit is the external appearance of a compound [1,2]
We found that APT after recrystallization gives tabular and long tabular crystal habits
Other solvents resulted in a mixture of crystal habits or irregular plates

Summary

Introduction

Polymorphism is the ability of a molecule to pack in different crystal lattices whereas crystal habit is the external appearance of a compound [1,2]. Crystal habit affects material attributes such as flow property, packing, compressibility, dissolution [5,6]. Blend uniformity, non-uniform filling of capsules on capsule filling machine, results in variation in content uniformity and dissolution. In this scenario, improvement of material attributes of API itself such as bulk density, flowability is of utmost importance [7]. Suitable crystal habit for the API can be evaluated among the possible crystal habits for improved flow and other material attributes Approaches such as solvent recrystallization, co-crystallization are used to develop a suitable crystal habit to improve the processing of powder blend at a large scale

Methods

Results

Conclusion