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Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

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Abstract

The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlation spectroscopy and evaluated for in vitro drug release and pharmacodynamic studies. The influence of increase in polymer concentration, ultrasonication time, and solvent evaporation rate on nanoparticle properties was investigated. The formulations were optimized based on the above characterization, and the formulation using 5% polymer, 3-min sonication time, and rota-evaporated was found to have the best drug entrapment efficiency of 64.09 ± 4.27% and size of 310.40 ± 11.42 nm. Based on SEM, nanoparticles were found to be spherical with a smooth surface. In vitro drug release data showed that nanoparticles sustained the nateglinide release for over 12 h compared to conventional tablets (Glinate 60 mg), and drug release was found to follow Fickian mechanism. In vivo studies showed that nanoparticles prolonged the antidiabetic activity of nateglinide in rats significantly (p ≤ 0.05) compared to the conventional tablets (Glinate 60 mg) over a period of 12 h. Accelerated stability data indicated that there was minimal to no change in drug entrapment efficiency.

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ACKNOWLEDGMENTS

The authors wish to thank Cadila Pharmaceuticals Ltd, Ahmadabad for providing them the drug sample. The authors also wish to thank Gland Pharma Ltd, Hyderabad for allowing them to carry out lyophilization studies in their facility.

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Correspondence to Prathima Srinivas.

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Kaleemuddin, M., Srinivas, P. Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide. AAPS PharmSciTech 14, 78–85 (2013). https://doi.org/10.1208/s12249-012-9887-z

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KEY WORDS

  • drug encapsulation efficiency
  • nanoparticles
  • poly Ɛ-caprolactone (PCL)
  • probe sonication