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Surface Engineering and Optimizing DepoFoam System: A Robust Quality by Design Approach for Optimal Drug Delivery, Stability, and Quality

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Abstract

Purpose

The study utilized non-ionic polymer macrogol to transform the surface properties of the DepoFoam drug carrier system, developing “surface-remodeled DepoFoam (SR-DFO)” following quality by design (QbD) principles. The primary objectives were to prolong drug delivery, reduce sudden releases, and enhance the overall quality and stability of DepoFoam. The research hypotheses are centered on the capability of macrogol-based surface modification to create an optimized drug delivery system with improved stability, extended drug release, and enhanced pharmacokinetic properties.

Methods

In this research, surface remodeling was achieved through a series of processes, including high-shear homogenizer-assisted double emulsification, PEGylation, and purification. The resulting SR-DFO formulations were comprehensively characterized for critical quality attributes. Optimization was conducted using the Box-Behnken design, resulting in significant enhancements in both quality and stability compared to conventional liposomes and unmodified DepoFoam.

Results

Comprehensive product characterization validates anticipated quality parameters: entrapment efficiency (86.16 ± 0.44%), drug-loading capacity (25.28 ± 0.07%), vesicle size (40.47 ± 0.1 µm), polydispersity index (PDI) of 0.051 ± 0.03, lipocrit of 90.67 ± 0.26%, and zeta potential of − 31.25 ± 3.25 mV. Remarkably, macrogol-based SR-DFO consistently sustains drug release above 90% for 168 h, devoid of sudden spikes, and maintains stability at 4 °C for 180 days. Mathematical models confirm drug release mechanisms’ validity. Moreover, this study emphasizes the critical influence of key materials like macrogol, phospholipids, triglycerides, and process variables on shaping product quality.

Conclusion

These findings highlight the inventive promise of macrogol-coated DFO in transforming drug delivery, quality, and stability. This research, driven by a well-formed hypothesis, meticulous execution, and precise data analysis, opens new horizons in polymer-based DepoFoam systems.

Graphical Abstract

First author: Jebastin Koilpillai, M.Pharm.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

ANOVA:

Analysis of variance

AOCS:

American Oil Chemists’ Society

API:

Active pharmaceutical ingredients

BBD:

Box-Behnken design

BCS:

Biopharmaceutics classification system

CI:

Creaming index

CMAs:

Critical material attributes

CPP:

Critical process parameter

CQAs:

Critical quality attributes

DL:

Drug loading

EE:

Entrapment efficiency

HR-SEM:

High-resolution scanning electron microscope

ICH:

International Conference on Harmonization

MLV:

Multilamellar liposome

MPS:

Mononuclear phagocytic system

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PV:

Peroxide value

QbD:

Quality by design

QTPP:

Quality target product profile

RES:

Reticuloendothelial system

RH:

Relative humidity

RPM:

Rotation per minute

SR-DFO:

Surface-remodeled DepoFoam

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Acknowledgements

The authors thank the SRM College of Pharmacy, SRMIST, for providing tremendous opportunities to accomplish this work.

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Authors and Affiliations

  1. Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, 603 203, Chengalpattu, Tamil Nadu, India

    Jebastin Koilpillai & Damodharan Narayanasamy

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  1. Jebastin Koilpillai
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Contributions

Conceptualization, data curation, and writing—original draft preparation: Jebastin Koilpillai. Writing—review and editing: Damodharan Narayanasamy. All authors contributed to the study’s conception and design and read and approved the final manuscript.

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Correspondence to Damodharan Narayanasamy.

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This is an observational study. No human volunteers or animals were utilized for the study. Therefore, the institutional Ethical Committee has confirmed that no ethical approval, clinical trial registration, or written informed consent is required for the study.

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No human volunteers were utilized for the study. Therefore, consent for publication is not required.

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Koilpillai, J., Narayanasamy, D. Surface Engineering and Optimizing DepoFoam System: A Robust Quality by Design Approach for Optimal Drug Delivery, Stability, and Quality. J Pharm Innov 19, 3 (2024). https://doi.org/10.1007/s12247-024-09808-y

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