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Fabrication of isradipine nanosuspension by anti-solvent microprecipitation–high-pressure homogenization method for enhancing dissolution rate and oral bioavailability

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Abstract

The aim of this study was to develop a nanosuspension of a highly hydrophobic drug, isradipine (ISR) by combination of anti-solvent microprecipitation and high-pressure homogenization to achieve the superior in vitro dissolution and in vivo pharmacokinetic profile. The nanosuspension was formulated using combination of stabilizers as vitamin E TPGS and sodium lauryl sulfate. The developed nanosuspension was characterized for particle size, shape, and zeta potential. The particle size of the developed ISR nanosuspension was observed to be approximately 538 nm (by laser diffraction) and 469 nm (by photon correlation spectroscopy) with −33.3 mV zeta potential. Scanning electron microscopy study revealed the good correlation with particle size measured by photon correlation spectroscopy and laser diffraction. The X-ray diffraction and differential scanning calorimetry showed that ISR was present as an amorphous state in the lyophilized form of nanosuspension. In vitro dissolution and saturation solubility study showed the dissolution rate of nanosuspensions (98.60 %) and saturation solubility (98.76 μg/ml) compared with the coarse drug (11.53 % and 14.1 μg/ml, respectively) had been significantly enhanced. The pharmacokinetic study showed that the nanosuspension exhibits increased in AUC0–48 by 2.0-fold compared to coarse suspension. Further, there was increased in C max and decreased in t max of ISR nanosuspension compared to coarse suspension of ISR. These studies proved that particle size reduction can influence ISR absorption in gastrointestinal tract and thus nanosuspension technology is responsible for enhancing oral bioavailability in rats.

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Acknowledgments

The authors would like to thank Kusum Healthcare, India and UGC‐SAP for providing financial assistance during the research work. The authors would like to thank AICTE/NAFETIC for providing the facility to conduct research.

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Authors declare that the experiments complied with current laws of India where these were performed.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga (E), Mumbai, 400 019, India

    Dnyanesh B. Shelar, Smita K. Pawar & Pradeep R. Vavia

  2. Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga (E), Mumbai, 400 019, India

    Pradeep R. Vavia

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  1. Dnyanesh B. Shelar
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  2. Smita K. Pawar
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  3. Pradeep R. Vavia
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Correspondence to Pradeep R. Vavia.

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Shelar, D.B., Pawar, S.K. & Vavia, P.R. Fabrication of isradipine nanosuspension by anti-solvent microprecipitation–high-pressure homogenization method for enhancing dissolution rate and oral bioavailability. Drug Deliv. and Transl. Res. 3, 384–391 (2013). https://doi.org/10.1007/s13346-012-0081-3

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  • DOI: https://doi.org/10.1007/s13346-012-0081-3

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