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<p>The objective of this study was to develop and characterize hot-melt extrusion (HME)-based gatifloxacin-loaded ophthalmic inserts (Gatiserts) to enhance ocular retention and reduce dosing frequency for bacterial conjunctivitis management. Gatiserts were formulated using hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and Poloxamer 407 via HME, ensuring uniform drug-polymer distribution. CaliCut technology enabled precise cutting, achieving consistent insert dimensions. Physicochemical characterization included XRD, DSC, ATR-FTIR, and SEM/EDS. In vitro drug release and kinetic modeling were performed, while molecular dynamics simulations assessed polymer-mucin interactions (MUC-1, MUC-4, MUC-16) to predict mucoadhesion. In vitro, antimicrobial activity against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> was performed, and in vivo, ocular irritation studies were conducted in rabbits. The optimized formulation (F10) exhibited well-defined dimensions (1.27&#xa0;mm diameter, 3.5&#xa0;mm length) with uniform drug distribution, attributed to HME and CaliCut precision. In vitro studies demonstrated sustained drug release (82.07% over 9&#xa0;h), following Peppas-Sahlin kinetics (R² = 0.9874). Molecular simulations indicated strong polymer-mucin interactions (docking scores: -9.7 to -10.3&#xa0;kcal/mol), suggesting enhanced mucoadhesion. XRD and DSC confirmed amorphous drug dispersion, while ATR-FTIR and SEM/EDS validated chemical stability and homogeneous drug distribution, respectively. In vitro, antimicrobial studies showed potent inhibition of <i>S. aureus</i> and <i>E. coli</i> over 24&#xa0;h. Gatiserts exhibited excellent biocompatibility (Draize score: 0) with no ocular irritation. The prolonged drug release, enhanced mucoadhesion, and excellent biocompatibility of Gatiserts suggest their potential for a significantly reduced dosing frequency compared to conventional eye drops, addressing rapid precorneal clearance and improving patient compliance in bacterial conjunctivitis management.</p> Graphical abstract <p></p>

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Development, in silico, in vitro, and in vivo evaluation of gatiserts: HME-based ophthalmic inserts for prolonged ocular delivery of gatifloxacin

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Amit Sharma,
  • Santosh Kumar Behera,
  • Jourawar Singh,
  • Jayesh Beladiya,
  • Devang Sheth,
  • Dhwani Rana,
  • Sapan Borah,
  • Aakanchha Jain,
  • Derajram Benival

摘要

The objective of this study was to develop and characterize hot-melt extrusion (HME)-based gatifloxacin-loaded ophthalmic inserts (Gatiserts) to enhance ocular retention and reduce dosing frequency for bacterial conjunctivitis management. Gatiserts were formulated using hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and Poloxamer 407 via HME, ensuring uniform drug-polymer distribution. CaliCut technology enabled precise cutting, achieving consistent insert dimensions. Physicochemical characterization included XRD, DSC, ATR-FTIR, and SEM/EDS. In vitro drug release and kinetic modeling were performed, while molecular dynamics simulations assessed polymer-mucin interactions (MUC-1, MUC-4, MUC-16) to predict mucoadhesion. In vitro, antimicrobial activity against Staphylococcus aureus and Escherichia coli was performed, and in vivo, ocular irritation studies were conducted in rabbits. The optimized formulation (F10) exhibited well-defined dimensions (1.27 mm diameter, 3.5 mm length) with uniform drug distribution, attributed to HME and CaliCut precision. In vitro studies demonstrated sustained drug release (82.07% over 9 h), following Peppas-Sahlin kinetics (R² = 0.9874). Molecular simulations indicated strong polymer-mucin interactions (docking scores: -9.7 to -10.3 kcal/mol), suggesting enhanced mucoadhesion. XRD and DSC confirmed amorphous drug dispersion, while ATR-FTIR and SEM/EDS validated chemical stability and homogeneous drug distribution, respectively. In vitro, antimicrobial studies showed potent inhibition of S. aureus and E. coli over 24 h. Gatiserts exhibited excellent biocompatibility (Draize score: 0) with no ocular irritation. The prolonged drug release, enhanced mucoadhesion, and excellent biocompatibility of Gatiserts suggest their potential for a significantly reduced dosing frequency compared to conventional eye drops, addressing rapid precorneal clearance and improving patient compliance in bacterial conjunctivitis management.

Graphical abstract