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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. KYDSCT’s College of Pharmacy, Sakegaon, Bhusawal 425 201, Dist., Jalgaon, MS, India

    Suraj S. Patil, Dipak D. Kumbhar, Jagdish V. Manwar, Rajesh G. Jadhao & Ravindra L. Bakal

  2. Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), New Delhi, India

    Rajesh G. Jadhao & Sharad Wakode

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  1. Suraj S. Patil
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Correspondence to Dipak D. Kumbhar.

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Patil, S.S., Kumbhar, D.D., Manwar, J.V. et al. Ultrasound-Assisted Facile Synthesis of Nanostructured Hybrid Vesicle for the Nasal Delivery of Indomethacin: Response Surface Optimization, Microstructure, and Stability. AAPS PharmSciTech 20, 97 (2019). https://doi.org/10.1208/s12249-018-1247-1

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