Fabrication and optimization of freeze-dried isoniazid-loaded poly-ε-caprolactone nanoparticles: Original scientific article

Eknath Kole; Yuvraj  Pawara; Atul  Chaudhari; Aniruddha Chatterjee; Jitendra B. Naik

doi:10.5599/admet.2774

Authors

Eknath Kole Department of Pharmaceutical Technology, University Institute of Chemical Technology, KBC North Maharashtra University, Jalgaon MS 425001, India. https://orcid.org/0000-0002-0782-581X
Yuvraj Pawara R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, MS 425405, India https://orcid.org/0009-0008-5879-2975
Atul Chaudhari Department of Pharmaceutical Technology, University Institute of Chemical Technology, KBC North Maharashtra University, Jalgaon MS 425001, India. https://orcid.org/0009-0005-7629-955X
Aniruddha Chatterjee Plastics Engineering Department, Plastindia International University, Vapi, Gujarat, India https://orcid.org/0000-0002-9559-2197
Jitendra B. Naik Department of Pharmaceutical Technology, University Institute of Chemical Technology, KBC North Maharashtra University, Jalgaon MS 425001, India https://orcid.org/0000-0001-8906-7903

DOI:

https://doi.org/10.5599/admet.2774

Keywords:

Lyophilization, nanoprecipitation, microreactor, sustained release, pulmonary tuberculosis

Abstract

Background: Microfluidic nanoprecipitation followed by freeze-drying would yield uniformly sized, stable nanoparticles by preserving their physicochemical property without compromising therapeutic performance. The isoniazid (INH)-loaded poly-ε-caprolactone (PCL) nanoparticles could be developed using a microfluidic technique for the management of tuberculosis. Experimental approach:The INH-loaded nanoparticles were fabricated via a microreactor-assisted nanoprecipitation method and optimization using a design of experiments factorial design approach. The resulting INH-PCL nanoformulation was characterized for particle size, polydispersity index (PDI), zeta potential (surface charge), Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis and field emission scanning electron microscope. Key results:The optimized nanoparticles exhibited an average particle size (248.4 ± 5.372 nm) and high encapsulation efficiency (82.26 ± 4.36 %). Thermal and spectroscopic analyses confirmed the absence of drug-polymer interactions, ensuring formulation integrity; stability studies under accelerated conditions demonstrated negligible changes in particle size, PDI, and zeta potential over the period of 6 months, indicating robust colloidal stability. A scanning electron microscopy study revealed rod-shaped nanoparticles with smooth surfaces. Lyophilization (freeze-drying) enhanced long-term stability, yielding a readily re-dispersible powder (reconstitution index 1.066). Following diffusion-controlled kinetics, in vitro drug release studies in phosphate buffer saline (pH 7.4) showed sustained drug release (92.45 % cumulative release over 48 h). Conclusion: Our results confirm that the INH-loaded PCL nanoformulation combines excellent stability, high drug-loading capacity, and sustained release, key attributes of effective tuberculosis therapy.

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