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Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres

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Abstract

The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations.

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Data Availability

All data analysed during this study are included in this published article.

Abbreviations

CPPs:

Critical process parameters

QBD:

Quality be design

CQA:

Critical Quality Attribute

QTPP:

Quality Target Product Profile

PLGA:

Poly Lactate co glycolate

FDA:

Food and Drug Administration

DOE:

Design of Experiments

DCM:

Dichloromethane

PVA:

Polyvinyl chloride

BBD:

Boc Behnken Design

PS:

Particle Size

EE:

Entrapment efficiency

BR:

Burst Release

DR:

Drug Release

THF:

Tetrahydrofuran

LC:

Drug Loading Content

DSC:

Differential scanning calorimetry

SEM:

Surface electron microscopy

PBS:

Phosphate-buffered saline

t1/2:

Half-life

MRT:

Mean Residence Time

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Acknowledgements

The authors specially acknowledge SRM College of pharmacy to perform all type of work for providing his valuable insights in drafting the article.

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  1. Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, 603203, India

    P. Lakshmikanth Reddy & Sangeetha Shanmugasundaram

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Contributions

Lakshmikanth Reddy P conducted experimental design, prepared the materials, collected the data, interpreted the results, and written the initial version of the manuscript. Sangeetha Shanmugasundaram supervised and corrected the manuscript. The final manuscript has been reviewed and endorsed by all authors.

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Correspondence to Sangeetha Shanmugasundaram.

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Reddy, P.L., Shanmugasundaram, S. Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres. AAPS PharmSciTech 25, 105 (2024). https://doi.org/10.1208/s12249-024-02830-w

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