Biopharmaceutical Optimisation of β-Cyclodextrin Inclusion Compounds

Summary

To improve the biopharmaceutical performance of the nonsteroidal anti-inflammatory drug piroxicam, inclusion compounds with β-cyclodextrin carrier have been prepared and studied for a wide range of chemical, physical and pharmaceutical properties.

Three bulk products were obtained, 2 by a process of freeze-drying (preparation A/1 and preparation A/2) and changing process parameters, and 1 by spray-drying (preparation B). The objective was to obtain tablets which provide a rapid-release dosage form of piroxicam.

Studies were conducted in vitro and in humans and compared tablets of the inclusion complex of piroxicam and β-cyclodextrin with marketed oral and parenteral dosage forms of piroxicam. Significant differences were found in plasma levels, maximum plasma concentration (C_max) and area under the plasma concentration-time curve (AUC), confirming that biopharmaceutical optimisation of the complexes can be achieved, leading to an overall pattern of absorption which is better than those presented by standard, non-complexed formulations of piroxicam (capsules, and ampoules for intramuscular use).

Evidence for a correlation between the 2 main physicopharmaceutical variables (solubilisation kinetics of the complex and dissolution rate of the tablet) and biopharmaceutical performances support the development of the product.