Homogeneity of amorphous solid dispersions – an example with KinetiSol^®

Abstract

KinetiSol^® is a high-shear, fusion-based technology capable of producing stable amorphous solid dispersions (ASDs) without the assistance of solvent. KinetiSol^® has proven successful with multiple challenging BCS class II and IV drugs, where drug properties like thermal instability or lack of appreciable solubility in volatile solvents make hot melt extrusion or spray drying unfeasible. However, there is a necessity to characterize the ASDs like those made by the KinetiSol^® process, in order to better understand whether KinetiSol^® is capable of homogeneously dispersing drug throughout a carrier in a short (<40 s) processing time. Our study utilized the high melting point, BCS class II drug, meloxicam, in order to evaluate the degree of homogeneity of 1, 5, and 10% w/w KinetiSol^®-processed samples. Powder blend homogeneity and content uniformity were evaluated, and all samples demonstrated a meloxicam concentration % relative standard deviation of ≤2.0%. SEM/EDS was utilized to map elemental distribution of the processed samples, which confirmed KinetiSol^®-processed materials were homogeneous at a 25 µm² area. Utilizing Raman spectroscopy, we were able to verify the amorphous content of the processed samples. Finally, we utilized ssNMR ¹H spin-lattice relaxation measurement to evaluate the molecular miscibility of meloxicam with the polymer at 1% w/w drug load, for the first time, and determined the processed sample was highly miscible at ∼200 nm scale. In conclusion, we determined the KinetiSol^® process is capable of producing ASDs that are homogeneously and molecularly well-dispersed drug-in-polymer at drug concentrations as low as 1% w/w.

Keywords:

• KinetiSol; amorphous solid dispersion; homogeneity; poorly water-soluble drug; ssNMR; SEM/EDS; Raman spectroscopy

Acknowledgment

The authors would like to acknowledge Dr. Andrei Dolocan for his assistance with the SEM/EDS experiments.

This work was presented in part as a poster at the American Association of Pharmaceutical Scientists Annual Meeting: PharmSci 360, November 2018, Washington, DC.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Graduate research assistant funding for Scott V. Jermain was provided by DisperSol Technologies, LLC.