Studies on the effect of different operational parameters on the crystallization kinetics of α-lactose monohydrate single crystals in aqueous solution

• Fast evaporation process adopted reduces the induction period of α-LM nucleation.
• Mutarotation between α-L and β-L in the solution is also controlled by this method.
• Growth inhibition at selected α-LM faces by β-L is also found suppressed pointedly.
• This method yields industrially favored needle-like α-LM crystals for DPI usage.
• Observed variation in nucleation parameters with σ follows theoretical estimates.

Supersaturation dependent nucleation, size and morphology of alpha-lactose monohydrate (α-LM) crystals from aqueous solution were investigated by adopting two different crystallization methods, slow evaporation and fast evaporation, in the supersaturation range between σ=0.05 and 1.30. The induction period of nucleation is comparatively long in case of slow evaporation and is very short in case of fast evaporation process as the interconversion between α-L and β-L is uncontrollable in the former and is under control in the latter case. Moreover α-LM crystals with tomahawk morphology were obtained throughout the supersaturation range by slow evaporation method whereas crystals with tomahawk, triangular and needle-like morphologies were obtained in supersaturation ranges σ=0.05–0.5, σ=0.5–0.9 and σ=0.9–1.30 respectively by fast evaporation method. Experimentally observed nucleation parameters were verified with theoretically deuced values. It is realized that the fast evaporation method employed in the present study is found to be highly efficient in controlling the interconversion between α-L and β-L as well as in suppressing the inhibitory activity of β molecule on the nucleation and growth of α-LM crystals when compared to conventional slow evaporation method and is successful in producing the industrially preferred needle-like crystals at high supersaturation ranges.