Determination of Amorphous Content of Lactose Samples by Solution Calorimetry

Abstract

Earlies studies suggest that solution calorimetry can be used to determine the extent of amorphous content of drug and excipient, when the solubility and dissolution rate of the compound in the chosen solvent are reasonably high. In the present study, the use of solution calorimetry for assessment of amorphous content of a sample that is not completely dissolved in a solvent was evaluated. Physical mixtures of lactose and spray‐dried lactose samples were analysed. The amorphous content of the physical mixtures and the spray‐dried samples varied from 0% to 100% determined by isothermal microcalorimetry. The enthalpy of solution (Δ_solH) was determined in water. The lactose samples were dissolved quickly in water. In addition, the enthalpy accompanied with an addition of a lactose sample in an over saturated aqueous solution (Δ_satH) (prepared from the corresponding lactose sample) was determined. The lactose sample did not completely dissolve in the over saturated aqueous solution. An excellent correlation was observed between Δ_solH and the amorphous content of the samples. Interestingly, there was a linear correlation also between Δ_satH and the amorphous content of the samples. Further, a linear relationship was observed between the Δ_satH and the Δ_solH of the samples. Therefore, solution calorimetry may represent a rapid and simple method for determining the amorphous content also in samples that are not completely dissolved in the solvent.

Key Words:

• Solution calorimetry
• Lactose
• Amorphous content