Physical chemical characterization of binary systems of prilocaine hydrochloride with triacetyl-β-cyclodextrin

Interaction products of prilocaine hydrochloride (PRL), a local anesthetic agent highly soluble in water, with triacetyl-beta-cyclodextrin (TA beta CD), a hydrophobic CD derivative practically insoluble in water, were prepared to estimate their suitability for the development of a prolonged-release dosage form of the drug. Equimolar PRL-TA beta CD solid systems were prepared by different methods (physical mixing, kneading, co-grinding, sealed-heating, coevaporation, spray-drying), in order to investigate their effectiveness and influence on the physical chemical properties of the end products. Differential scanning calorimetry, X-ray powder diffractometry, FTIR spectroscopy and environmental scanning electron microscopy (ESEM) were used for the solid-state characterization of the different PRL-TA beta CD systems, whereas their in vitro dissolution properties were determined according to the dispersed amount method. On the basis of the overall solid-state studies results, the ability of the different methods to bring about effective drug-TA beta CD interactions varied in the order: spray-drying > co-grinding a parts per thousand coevaporation > sealed-heating > kneading > physical mixing. This rank order was not observed in dissolution studies, where coevaporated, kneaded and sealed-heated products exhibited very similar profiles, practically superimposable to that of pure drug and physical mixture, all reaching 100% dissolution in less than 10 min. Evidently, all these techniques gave rise only to weak surface interactions, rapidly destroyed in solution. Some decrease in dissolution rate was observed for co-ground system (100% dissolved drug after 40 min), probably due to electrostatic and aggregation phenomena associated with the high-energy mechanical treatment. A very different behaviour was shown by the spray-dried system, which give rise to an almost linear slow-dissolving profile, reaching 100% of dissolved drug after 420 min, suggesting in this case the formation of an actual inclusion compound. Thus, the drug-TA beta CD product obtained by spray-drying was selected as the best candidate for the future development of a suitable prolonged-release oral dosage form of PRL.