Investigation of preparation parameters of nanosuspension by top-down media milling to improve the dissolution of poorly water-soluble glyburide

The objective of this study was to identify and optimize formulation and process variables affecting characteristic and scale-up of nanosuspension manufacturing process on bead mill considering industrial perspective. Formulation factors evaluated were ratio of polymer to drug and ratio of surfactant to drug, whereas process parameters were milling time and milling speed. Responses measured in this study include zeta potential and mean particle size d(90). The test revealed that ratio of polymer to drug and milling speed have significant effect on zeta potential whereas milling time and milling speed have significant effect on the particle size distribution of nanosuspension. The X-ray powder diffraction pattern of drug milled at high and low speed reveals no form conversion when compared with unmilled drug. The formulated nanosuspension has shown a faster dissolution profile (98.97% in 10 min), relative to that of raw glyburide (18.17% in 10 min), mainly due to the formation of nanosized particles. The ANOVA test revealed that there was no significant difference in the dissolution profiles of fresh and aged nanosuspension. These results indicate the suitability of formulation procedure for preparation of nanosized poorly water-soluble drug with significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect.

Glyburide nanosuspension was prepared by dispersing the drug and the stabilizers in the milling media and then subjected to milling chamber of bead mill for particle size reduction at a feed rate of 100ml/min at 2800 rpm for 6.5 h at 18–20°C . The formed nanosuspension has shown an enhancement in the dissolution rate when compared with the unmilled drug.Figure optionsDownload as PowerPoint slide