Formulation development and optimization of alpha ketoglutarate nanoparticles for cyanide poisoning

The purpose of this research work was to formulate and evaluate alpha ketoglutarate nanoparticles as dry powder inhaler for treatment of cyanide poisoning. Non-polymeric particles were prepared by nano-precipitation technique using various stabilizers. Selection of co-solvent and stabilizer was a key to produce stabilized particles. A combination of lutrol F68 and PVA as a crystal growth inhibitor seems to be best in achieving minimum particle size of 110.2 nm. On the basis of preliminary trials a Box-Behnken statistical design was employed to study the effect of independent variables, drug concentration (X₁), stirring speed (X₂), stirring time (X₃), PVA concentration (X₄), poloxomer concentration (X₅) and volume of co-solvent (X₆) on average particle size. Particle size varied from 110 to 875 nm depending upon the significant terms. Optimized formulation was predicted at drug concentration (50 μg/ml), stirring speed (640 rpm), stirring time (1 min), PVA concentration (1%), poloxomer concentration (1.69%) and volume of co-solvent (30 ml) with 104.6% experimental validity. The nanosized particles were further characterized by X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FT-IR) analysis. The results of particle characterization indicate that there was no physical disparity when compared with the commercial α-KG sample.