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.

Graphical AbstractNon-polymeric particles were prepared by nano-precipitation technique using various stabilizers. 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, on average particle size. 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 antisolvent (30 ml) with 104.6% experimental validity.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► The objective of the present study relates to formulation development and evaluation of alpha ketoglutarate nanoparticles as dry powder inhaler for treatment of cyanide poisoning. ► The particles were prepared by antisolvent precipitation technique using PVA and Lutrol F68 as stabilizer. The influence of some preparative variables such as drug concentration, type and concentration of different stabilizers (alone or in combination) and antisolvent volume have been investigated in order to control and optimize the process. box-behnken statistical design was employed to evaluate the combined effects of the selected variables on average particle size. ► The particles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Malvern, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FT-IR).