Solid-state characterization studies and effect of PEG 20000 and P90G on particle size reduction and stability of complexed glimepiride nanocrystals

Objective: The objective of the present study is to formulate and characterize the properties of complexed glimepiride nanocrystals (GLP) by various techniques at different stages of its development, and to study the effect of PEG 20000 and P90G on particle size reduction and stability of nanocrystals. Method: Precipitated (GLP-PEG) and complexed NCs (GLP-PEG-P90G) of glimepiride were characterized for particle size, size distribution, zeta potential and stability assessment using photon correlation spectroscopy (PCS). The crystallinity was analyzed using differential scanning calorimetry (DSC) and X-ray powder diffraction spectroscopy (XRPD). The surface morphology and chemical stability were assessed by means of scanning electron microscopy (SEM) and infrared spectroscopy (FTIR). Results: A formulation with drugepolymer ratio of 1:1 was most ideal in developing stable NCs as it exhibited smaller particle size and high stability. A high zeta potential was observed in all NCs after complexation indicating improved stability. DSC and XRPD studies showed no change in crystallinity after complexation. SEM analysis of complexed NCs showed presence of spherical shape particles (size below 1 µm) with a lipid coat on the surface. Stability studies on optimized formulation (F1) revealed no change in particle size during 3-month period. FTIR studies prove that the chemical identity of GLP was preserved in the samples and the formulation was stable. Conclusion: Solid-state characterization studies reveal that complexed GLP NCs are promising carriers for drug delivery and they can be safely and effectively used in design of various formulations. Also, PEG 20000 and P90G are excellent polymer and lipid for particle size reduction (nanonization) and stabilization of nanocrystals.

Key words: Lipid nanocrystals, Precipitation, Surface properties, Crystallinity, Nanonization.