Crystallization of Alpha-Lactose Monohydrate (α-LM) from Aqueous Solution through Gas-Phase Diffusion and Anti-Solvent Crystallization Methods

Abstract

Alpha-lactose monohydrate (α-LM) is an important disaccharide and is widely used as a carrier in dry powder inhaler (DPI) and also used as a main ingredient in most of the dairy products. The quality, shelf-life and bio-pharmaceutical performance of the DPI and dairy products depends on the size, size distribution and morphology of α-LM. Crystallization of α-LM is an important purification step in refining lactose from whey solutions. Nucleation of α-LM occurred only after a very long time ~134 h and this is a major drawback leading to the uneven distribution and growth of larger crystals. To overcome these problems, we employed two different techniques, (i) gas-phase diffusion and (ii) anti-solvent crystallization to reduce the nucleation time and to control the size and morphology of α-LM. The aqueous solution of α-LM was mixed with different volumes of organic solvents like, DMSO and ethanol. The different levels of supersaturation generated through gas-phase diffusion and anti-solvent crystallization leads variation in the nucleation time, size and morphology of the crystals. The crystals grown by these two methods were analyzed by optical microscope and by PXRD and DSC. By employing gas-phase diffusion crystallization process we could able to crystallize α-LM crystals within shorter induction time when compared to conventional crystallization method and also α-LM crystals with high purity when compared to anti-solvent crystallization method.