β‐Cyclodextrin Inclusion Complexation by Milling

Abstract

The study involved the complexation of nimesulide with β-cyclodextrin (β-CyD) by milling. Nimesulide and β-CyD were mixed in the ratios 1:1, 1:2, 1:3 and 1:4 by weight. Each mixture was ground in a ball mill at 50 rev min−1 for 6, 12, 24 and 48 h. The samples were subjected to dissolution studies, differential scanning calorimetry and X-ray diffraction studies and were also evaluated for anti-inflammatory and analgesic activity. The sample containing the 1:4 ratio milled for 6 and 12 h exhibited a lower T90 value compared with nimesulide, ball-milled nimesulide and the freeze-dried complex. Increasing the milling time to 24 or 48 h further increased the T90 (time required for 90% of the drug to dissolve) value. The dissolution rate constant for nimesulide increased with an increase in β-CyD concentration. Milled samples (1:4 ratio milled for 6 and 12 h) also showed significant anti-inflammatory and analgesic activity. The results showed an improved rate of nimesulide absorption and hence better bioavailability by inclusion complex formation of the drug with β-CyD.