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Quality by Design (QbD) based Formulation Optimization of Isoniazid Loaded Novel Nanostructured Lipid Carriers for Controlled Release Effect

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Abstract

Background

The emergence of resistance to isoniazid is widespread associated with high drug doses and longer duration of treatment which reduces the probability of getting success in the cure of tuberculosis.

Purpose

This research work aimed to develop novel nanostructured lipid carriers (NLCs) for the controlled release effect of isoniazid (INZ) to reduce the drug dose, dosing frequency, and dose-associated adverse effects.

Methods

Quality by Design (QbD) approach was used to optimize the lipid combination for NLCs using response surface methodology (RSM)-central composite rotatable design (CCRD). The independent factors were investigated for their effects on dependent variables. The formulation with maximum desirability value was selected as an optimized formulation and selected for various evaluation parameters.

Results

The final optimized (INZ-NLC) formulation was evaluated for drug release kinetics and found to follow the Korsmeyer-Peppas model indicating an erosion-controlled non-Fickian drug release process. The polydispersity index (PDI) and zeta potential (ZP) were also measured. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) study revealed a loss of crystallinity of the drug within the INZ-NLC formulation. Transmission electron microscope (TEM) photomicrographs showed the drug-loaded spherical particles of the optimized nanocarrier formulation. Stability studies suggested that the optimized INZ-NLC formulation was best stable for 6 months.

Conclusion

This study reports the successful development of the lipid combination to provide a controlled release effect to a hydrophilic drug (isoniazid) for reducing the dose and dosing frequency after pulmonary administration for better management in the treatment of tuberculosis.

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Availability of Data and Materials

The represented data is original, unbiased, and accurate representation of research.

Code Availability

The trail versions of both the software Design Expert® v 13 and Prism 9.1.0® were used to compute the presented results.

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Acknowledgements

The authors thank Mrs. Chanda, Department of Electron Microscopy, AIIMS, New Delhi for the TEM analysis and Dr. Ashish Aggarwal, Department of Physics, Guru Jambheshwar University of Science and Technology, Hisar for the PXRD analysis. The authors acknowledge that this work is a part of PhD research work.

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Authors and Affiliations

  1. School of Medical and Allied Sciences, G. D. Goenka University, Gurugram, 122102, India

    Shaveta Ahalwat

  2. Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India

    Shaveta Ahalwat, Dinesh Chandra Bhatt & Surbhi Rohilla

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  1. Shaveta Ahalwat
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Correspondence to Shaveta Ahalwat.

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This formulation is under investigation for its in vitro pulmonary behaviour, in vivo pharmacokinetics, and toxicity studies.

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Ahalwat, S., Bhatt, D.C. & Rohilla, S. Quality by Design (QbD) based Formulation Optimization of Isoniazid Loaded Novel Nanostructured Lipid Carriers for Controlled Release Effect. J Pharm Innov 18, 1685–1700 (2023). https://doi.org/10.1007/s12247-023-09749-y

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