TY - JOUR

T1 - Numerical Mechanistic Modelling of Drug Release from Solvent-Removal Zein-Based In Situ Gel

AU - Senarat, Setthapong

AU - Pornsawad, Pornsarp

AU - Lertsuphotvanit, Nutdanai

AU - Østergaard, Jesper

AU - Phaechamud, Thawatchai

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - The development of effective drug delivery systems remains a focus of extensive research to enhance therapeutic outcomes. Among these, in situ forming gels (ISG) have emerged as a promising avenue for controlled drug release. This research focuses on the mathematical modeling of levofloxacin HCl (Lv) release from zein-based ISG using the cup method, aiming to mimic the environment of a periodontal pocket. The drug release behavior of the ISGs was investigated through experimental observations and numerical simulations employing forward and central difference formula. Notably, the experimental data for drug release from the 20% w/w zein-based ISG formulations closely aligned with the simulations obtained from numerical mechanistic modeling. In summary, 20% w/w zein-based ISG formulations demonstrated nearly complete drug release with the maximum drug concentration at the edge of the matrix phase values consistently around 100–105%, while 25% w/w zein-based ISG formulations exhibited somewhat lower drug release extents, with values ranging from 70–90%. Additionally, the rate of drug transport from the polymer matrix to the external phase influenced initial release rates, resulting in a slower release. The utilization of glycerol formal as a solvent extended drug release further than dimethyl sulfoxide, thanks to denser matrices formed by high-loading polymers that acted as robust barriers to solvent removal and drug diffusion. Furthermore, UV-vis imaging was utilized to visualize the matrix formation process and solvent diffusion within the ISGs. The imaging results offered valuable insights into the matrix formation kinetics, controlled drug release mechanisms, and the influence of solvent properties on drug diffusion. The combination of mathematical modeling and experimental visualization provides a comprehensive understanding of drug release from zein-based ISGs and offers a foundation for tailored drug delivery strategies.

AB - The development of effective drug delivery systems remains a focus of extensive research to enhance therapeutic outcomes. Among these, in situ forming gels (ISG) have emerged as a promising avenue for controlled drug release. This research focuses on the mathematical modeling of levofloxacin HCl (Lv) release from zein-based ISG using the cup method, aiming to mimic the environment of a periodontal pocket. The drug release behavior of the ISGs was investigated through experimental observations and numerical simulations employing forward and central difference formula. Notably, the experimental data for drug release from the 20% w/w zein-based ISG formulations closely aligned with the simulations obtained from numerical mechanistic modeling. In summary, 20% w/w zein-based ISG formulations demonstrated nearly complete drug release with the maximum drug concentration at the edge of the matrix phase values consistently around 100–105%, while 25% w/w zein-based ISG formulations exhibited somewhat lower drug release extents, with values ranging from 70–90%. Additionally, the rate of drug transport from the polymer matrix to the external phase influenced initial release rates, resulting in a slower release. The utilization of glycerol formal as a solvent extended drug release further than dimethyl sulfoxide, thanks to denser matrices formed by high-loading polymers that acted as robust barriers to solvent removal and drug diffusion. Furthermore, UV-vis imaging was utilized to visualize the matrix formation process and solvent diffusion within the ISGs. The imaging results offered valuable insights into the matrix formation kinetics, controlled drug release mechanisms, and the influence of solvent properties on drug diffusion. The combination of mathematical modeling and experimental visualization provides a comprehensive understanding of drug release from zein-based ISGs and offers a foundation for tailored drug delivery strategies.

KW - drug release kinetics

KW - in situ forming gel

KW - levofloxacin

KW - mechanistic model

KW - numerical simulation

KW - zein

U2 - 10.3390/pharmaceutics15102401

DO - 10.3390/pharmaceutics15102401

M3 - Journal article

C2 - 37896160

AN - SCOPUS:85175098873

VL - 15

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 10

M1 - 2401

ER -