Influence of preparation methodology on solid-state properties of an acidic drug-cyclodextrin system.

Abstract

We have investigated the influence of processing variables on the solid-state of a model drug, flurbiprofen, in cyclodextrin-based systems and its effect on dissolution behaviour of the drug. The interaction between flurbiprofen and hydroxypropyl beta-cyclodextrin (HP-beta-CyD) was studied by NMR spectroscopy and phase solubility studies. Binary systems containing flurbiprofen and HP-beta-CyD or povidone (polyvinylpyrrolidone) K30, prepared by various processes, were characterized by FTIR, DSC, XRD and dissolution studies. HP-beta-CyD enhanced the solubility of flurbiprofen and increased dissolution rates from binary systems. It was found to be superior to povidone K30 in producing higher dissolution rates. The method of preparation of the binary systems and the agents used were found to have a major influence on the final solid-state of flurbiprofen. Solvents and processing conditions favouring greater interaction between flurbiprofen and the cyclodextrin during the preparation process resulted in greater extent of drug-cyclodextrin association and/or greater amorphization of the drug. Use of ammonia during the preparation of binary systems yielded solids from which very rapid drug dissolution was achieved, due to a higher extent of molecular dispersion of the drug. Processing variables therefore could significantly influence the solid-state of a drug in cyclodextrin-based formulations and thereby affect its dissolution behaviour. This could lead to significant effects on the in-vivo performance of the formulation.