Rapid amorphization of molecular crystals by absorption of solvent molecules in the presence of hydrophilic matrices

Abstract

Two organic molecular crystalline species, ibuprophen (IB) and indomethacine (IM) were subjected to methanol absorption in the presence of hydrophilic organic matrix, hydroxypropyl methylcellulose (HPMC). While spraying of 8–10% methanol or water on the drug–matrix mixture decreased the subsequent milling time for amorphization, absorption of methanol in a closed container caused spontaneous amorphization of IB was observed to give a nanocomposites with macroscopic agglomerates up to 250 μm after methanol absorption for overnight. Gentle mechanical homogenization under saturated methanol vapor with a newly developed apparatus, a tandem rotation mill (TRM), brought about homogeneous grains of IB-HPMC nanocomposites with the average particle size, 30 μm. We observed amorphous particles of IB in 60 nm regime dispersed in HPMC matrix under a transmission electron microscope (TEM). In the case of IM, mechanical homogenization with TRM was indispensable to obtain similar nanocomposites with HPMC.