CHARACTERIZATION OF THE SURFACE ENERGETICS OF MILLED DL-PROPRANOLOL HYDROCHLORIDE USING INVERSE GAS-CHROMATOGRAPHY AND MOLECULAR MODELING

Inverse gas chromatography (IGC) has been successfully used to charact erise the nature of the surface of samples of dl-propranolol hydrochlo ride which have been produced under conditions of increasing milling i ntensity. It has been shown that the surface becomes increasingly more energetic as indicated by an increase in the dispersive component of the surface free energy and more electron donating as indicated by the adsorption of tetrahydrofuran and dichloromethane. Both effects incre ase until at a critical particle size a plateau is reached with no fur ther change with a reduction in particle size. The critical particle s ize coincides with the brittle ductile transition determined previousl y by mechanical measurement. Molecular modelling was used to predict w hich surfaces would predominate by making use of calculations of attac hment energies. The face which had the lowest attachment was postulate d to be the plane which predominately fractures during high intensity milling. Visualisation showed that the pi-electron rich naphthalene mo iety of dl-propranolol hydrochloride dominated this surface supporting the data from IGC. (C) 1998 Elsevier Science B.V. All rights reserved .