Morphology of Crystals of α-Lactose Hydrate Grown from Aqueous Solution

Abstract

When dissolved in aqueous solution, R-lactose, whether originally in the anhydrous or the monohydrated form, readily undergoes mutarotation to yield the β isomer. At equilibrium, which is reached in 6.5 h at 292 K and more rapidly with increasing temperatures, the latter is present to the extent of ca. 60% w/w. At saturation, R-lactose hydrate precipitates from this solution being considerably less soluble than the β form. The resulting crystals have a highly asymmetric, tomahawk shaped morphology characterized by large {01 h1} faces. It is confirmed that this shape arises from growth inhibition due to the incorporation of the β isomer in the {01 h1} sectors of the crystals coupled with a characteristic lack of growth in the [01 h0] direction. Growth under conditions that restrict the formation of the β isomer yields more symmetrically shaped, needlelike crystals. These show a gradual transition to the tomahawk shape as the concentration of the β isomer in solution and hence in the crystal is increased. An assessment is made of the degree of incorporation of the β isomer into the crystal, its distribution and its influence on the defect structure of the material.

The Measurement of the β/α Anomer Composition Within Amorphous Lactose Prepared by Spray and Freeze Drying Using a Simple 1H-NMR Method

“…The exact composition and the time taken to reach equilibrium between the two forms are dependent on concentration, pH and temperature. Typical equilibration times are reported to fall within the 3.5 to 6.5 h range and it is generally accepted that the mutarotation of lactose in aqueous solution follows first order kinetics for reversible reactions approaching equilibrium (13)(14)(15).…”

Effect of galacto-oligosaccharide concentration on the kinetics of lactose crystallisation

“…The observed habit transition of a-lactose monohydrate in the presence of increasing GOS levels was a reversal of that described for increasing b-lactose concentration (Raghavan et al, 2000). The transition in terms of b-lactose was first noted by van Kreveld and Michaels (1965).…”

“…The transition in terms of b-lactose was first noted by van Kreveld and Michaels (1965). The major observations made by Michaels and van Kreveld (1966) and Raghavan et al (2000) are presented in Fig. 5, stating the change in habit from a needle shaped appearance at 0% b-lactose via a cubic structure to the tomahawk shape as the mutarotation equilibrium level is reached.…”

Crystallization of spray-dried lactose/protein mixtures in humid air

“…In terms of crystallization from aqueous solution, the alactose monohydrate phase is the most extensively studied [23,24]. Most studies have been carried out in conditions where the a-and b-isomers are both present at ratios determined by the equilibrium mutarotation of the isomers [23][24][25].…”

“…Most studies have been carried out in conditions where the a-and b-isomers are both present at ratios determined by the equilibrium mutarotation of the isomers [23][24][25]. This means a-lactose monohydrate has a propensity to form as a pure crystalline phase even in the presence of large amounts of the b-isomer [6,26].…”