Polymorphic change of a triglyceride base in hot melt coating process and stability acceleration by tempering process

Abstract

In this study, the influence of hot melt coating condition on polymorphic change of a triglyceride base, hydrogenated soybean oil (HSO) was studied. Metoprolol tartrate was used as a water-soluble model drug. Coated pellets were prepared by spraying drug-lipid dispersion onto nonpareil seeds. A tempering process was employed in order to achieve the stable form of HSO. Differential scanning calorimetry was used to simulate the coating and tempering conditions prior to the processing and to characterize polymorphic change together with powder X-ray diffractometry and hot stage microscopy. Coated pellets possessed three polymorphic forms of HSO but only the stable form was dominant after tempering. Tempered pellets presented crystal growth of HSO with 1-2 μm microstructure elements. This morphological change led to the reduced porosity and increased surface area of the pellets as well as the increased drug release. The release profile was attributable to the tempering temperature. In order to stabilize the drug release, the tempering process was suggested to perform at the temperature below the melting point of the unstable form.