The influence of crystallization conditions on the morphology of lactose intended for use as a carrier for dry powder aerosols

Lactose has been widely used as a carrier for inhalation aerosols. The carr ier morphology is believed to affect the delivery of the drug. The aim of t his study was to investigate the effects of crystallization conditions on t he morphology of a-lactose monohydrate intended for use as the carrier for dry powder aerosols. The crystallization of lactose was carried out from aqueous solutions at di fferent supersaturations, temperatures, different stages of crystallization and in the presence of different water-miscible organic solvents. The majo rity of lactose crystals were found to be either tomahawk-shaped or pyramid al after crystallization at an initial lactose concentration between 33-43% w/w, but these became prismatic if the lactose concentration was increased to 50% w/w. A further increase in the lactose concentration to 60% w/w led to the preparation of elongated cuboidal crystals. Higher initial lactose concentrations tended to result in the crystallization of more elongated pa rticles. Crystallization at 40 degrees C was shown to prepare lactose cryst als with a more regular shape and a smoother surface than those crystallize d at 0 degrees C. Lactose particles generated during the later stage of cry stal lization were found to be more regular in shape with a smoother surfac e than those prepared in the earlier stage. The addition of 10% (v/v) metha nol or ethanol or acetone to the mother liquor increased the growth rate of lactose particles whereas addition of propanol or glycerine inhibited the rate of crystal growth. Lactose crystals prepared in the presence of glycer ine were more regularly shaped with a smoother surface than those prepared in the presence of ethanol or acetone. All the resultant crystals were show n to comprise a-lactose monohydrate. Lactose crystals could be prepared with a precisely defined morphology by m eans of carefully controlling the crystallization conditions.