Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

Abstract

It is demonstrated that acoustic levitation is able to produce amorphous forms from a variety of organic molecular compounds with different glass forming abilities. This can lead to enhanced solubility for pharmaceutical applications. High-energy x-ray experiments show that several viscous gels form from saturated pharmaceutical drug solutions after 10–20 min of levitation at room temperature, most of which can be frozen in solid form. Laser heating of ultrasonically levitated drugs can also result in the vitrification of molecular liquids, which is not attainable using conventional amorphization methods.

Alternate abstract:

Plain Language Summary

Making fast acting drugs is a goal of almost every pharmaceutical company. The route of delivering them in the forms of amorphous solids has long been recognized as a possible way to enhance dissolution rates and increase both solubility and bioavailability. The development in this direction is becoming increasingly important due to the emergence of many new drugs that are virtually insoluble in their crystalline forms. In this experimental paper, we exploit the technique of acoustic levitation of liquid droplets and present two new methods for forming amorphous solids from molecular liquids and solutions of a wide range of pharmaceutical drugs of varying chemical structures and different functions. One method combines acoustic levitation with solvent evaporation and produces amorphous gels of the drugs; the other integrates laser-heating induced melting and subsequent cooling with acoustic levitation and turns drugs that are usually obtained in crystalline, functionally less effective forms to more desirable amorphous forms (a process also known as vitrification in materials science and engineering). Proof-of-principle applications of the two containerless methods are demonstrated with in situ characterizations of the samples by use of high-energy x-ray diffraction at the Advanced Photon Source.

We anticipate that such containerless processing methods, combined with sophisticated, high-throughput droplet-forming or dispensing methods, may provide practical routes for scaled-up productions of amorphous drugs.