engleski

Zaleplon co-ground complexes with natural and polymeric beta-cyclodextrin

In this study, we compared the suitability of parent ß- cyclodextrin (ßCD) and its water soluble polymeric derivative (PßCD) as co-grinding additives aimed to enhance the solubility of zaleplon (ZAL), a hypnotic drug. Equimolar drug/carrier mixtures were co-ground in a highenergy micromill over different time intervals. Data obtained by differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy showed a higher affinity of ZAL for the solid state interaction with PßCD, resulting in powders with lower relative drug crystallinity (RDC) compared to that obtained with natural ßCD (RDC = 51.10 and 12.5 % for complexes with ßCD and PßCD co-grounded for 90 min, respectively). On the other hand, grinding the drug alone did not result in a significant reduction of the drug crystallinity (RDC = 99.87 % for the sample ground for 90 min). Although 1H-NMR spectroscopy confirmed that both coground products were readily converted into inclusion complexes upon dissolution in water, they presented different dissolution properties. The dissolution velocity of co-ground complex with PßCD was 25 % faster compared to that prepared with the parent ßCD and almost double compared to that of the drug alone, irrespective of the pH value of the dissolution media. This clearly demonstrated the suitability of co-ground ZAL/PßCD complex in the development of an immediate release oral formulation of ZAL.

zaleplon; cyclodextrin; solid state analysis; solubility

nije evidentirano