AAPS PharmSciTech

, 20:97 | Cite as

Ultrasound-Assisted Facile Synthesis of Nanostructured Hybrid Vesicle for the Nasal Delivery of Indomethacin: Response Surface Optimization, Microstructure, and Stability

  • Suraj S. Patil
  • Dipak D. KumbharEmail author
  • Jagdish V. Manwar
  • Rajesh G. Jadhao
  • Ravindra L. Bakal
  • Sharad Wakode
Research Article


This work is devoted to design a novel nanostructured hybrid vesicle (NHV) made of lecithin and an acrylate/C10-C30 alkyl acrylate for the nasal delivery of a model active indomethacin (IND), and further to probe its microstructure, intermolecular interactions, drug release behavior, ex vivo permeation, and stability. NHVs were prepared by cavitation technology employing RSM-based central composite design (CCD). Amount of lecithin (X1), power of ultrasound (X2), and sonication time (X3) were selected as three independent variables while the studied response included Z-Avg (nm), polydispersity index (PDI), and zeta potential (mV). The designed system (NHV) was investigated through dynamic (DLS) and electrophoretic light scattering (ELS), attenuated total reflectance (ATR-FTIR), oscillatory measurement (stress and frequency sweep), and transmission electron microscopy (TEM). CCD was found useful in optimizing NHV. An optimized formulation (S6) had Z-Avg 80 nm, PDI 0.2, and zeta potential of − 43.26 mV. Morphology investigation revealed spherical vesicles with smaller TEM diameters (the largest particle being 52.26 nm). ATR analysis demonstrated significant intermolecular interactions among the drug (IND) and the components of vesicles. The designed vesicles had an elastic predominance and displayed supercase II (n > 1) type of drug release. Besides, the vesicles possessed potential to transport IND across the nasal mucosa with the steady-state flux (μg/cm2/h) and permeability coefficient (cm/h) of 26.61 and 13.30 × 10−3, respectively. NHV exhibited an exceptional stability involving a combination of electrostatic and steric interactions while the histopathology investigation confirmed their safety for nasal administration.


indomethacin hybrid vesicle microstructure supercase II transport nasal delivery 



Authors wish to acknowledge North Maharashtra University (NMU), Jalgaon, for providing Zetasizer facility, HR Patel College of Pharmacy Shirpur for NanoPlus facility, and Indian Institute of Technology (IIT), Mumbai, India, for TEM analysis.

Supplementary material

12249_2018_1247_MOESM1_ESM.docx (70 kb)
ESM 1 (DOCX 70 kb)
12249_2018_1247_MOESM2_ESM.docx (2.4 mb)
ESM 2 (DOCX 2482 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Suraj S. Patil
    • 1
  • Dipak D. Kumbhar
    • 1
    Email author
  • Jagdish V. Manwar
    • 1
  • Rajesh G. Jadhao
    • 1
    • 2
  • Ravindra L. Bakal
    • 1
  • Sharad Wakode
    • 2
  1. 1.KYDSCT’s College of PharmacyJalgaonIndia
  2. 2.Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR)New DelhiIndia

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