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Background <p>Ezetimibe is a Biopharmaceutics Classification System (BCS) class II drug characterized by poor aqueous solubility and dissolution-limited oral absorption, resulting in variable bioavailability despite high intestinal permeability. Enhancing dissolution while achieving site-specific intestinal delivery remains a significant formulation challenge.</p> Objective <p>To design and evaluate a pH-sensitive solid nanomatrix system capable of enhancing dissolution, improving physical stability, and enabling intestinal-specific release of ezetimibe.</p> Methods <p>A dual-component nanomatrix comprising mesoporous silica (Syloid AL1FP) and enteric polymer (Eudragit S100) was developed using a solvent evaporation technique. Formulations (NM1–NM9) were characterized for drug content, particle size distribution, saturation solubility, surface area (BET), pore volume, solid-state properties (DSC, XRD), morphology (SEM, optical microscopy), and pH-dependent dissolution behavior. Statistical analysis was performed using ANOVA, Tukey’s test, and model-independent parameters.</p> Results <p>Optimized formulations demonstrated high drug content uniformity and nanoscale particle size (D₅₀ ≈ 185–200 nm). An approximately 8-fold increase in saturation solubility was observed compared with pure ezetimibe. BET analysis confirmed drug adsorption within the mesoporous silica network, evidenced by reduced surface area and pore volume. DSC and XRD analyses indicated predominant amorphization without polymorphic transitions. SEM and optical microscopy revealed porous, non-crystalline morphology consistent with molecular dispersion. In vitro dissolution studies showed negligible drug release in acidic medium, controlled release in intestinal pH, and rapid release at pH 7.4, with NM1 achieving &gt;95% release within 60 minutes. Statistical evaluation confirmed the significantly enhanced dissolution performance of optimized formulations (p &lt; 0.05).</p> Conclusion <p>The pH-sensitive solid nanomatrix system effectively enhances solubility, dissolution rate, and physical stability of ezetimibe through nanoconfinement within mesoporous silica and polymeric encapsulation. This scalable strategy offers a promising approach for improving the biopharmaceutical performance of poorly water-soluble drugs requiring intestinal-specific delivery.</p>

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Formulation and Characterization of pH-Sensitive Ezetimibe Nanomatrix for Enhanced Biopharmaceutical Performance

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Minal Narkhede,
  • Omkar Daware,
  • Chetana Belkare

摘要

Background

Ezetimibe is a Biopharmaceutics Classification System (BCS) class II drug characterized by poor aqueous solubility and dissolution-limited oral absorption, resulting in variable bioavailability despite high intestinal permeability. Enhancing dissolution while achieving site-specific intestinal delivery remains a significant formulation challenge.

Objective

To design and evaluate a pH-sensitive solid nanomatrix system capable of enhancing dissolution, improving physical stability, and enabling intestinal-specific release of ezetimibe.

Methods

A dual-component nanomatrix comprising mesoporous silica (Syloid AL1FP) and enteric polymer (Eudragit S100) was developed using a solvent evaporation technique. Formulations (NM1–NM9) were characterized for drug content, particle size distribution, saturation solubility, surface area (BET), pore volume, solid-state properties (DSC, XRD), morphology (SEM, optical microscopy), and pH-dependent dissolution behavior. Statistical analysis was performed using ANOVA, Tukey’s test, and model-independent parameters.

Results

Optimized formulations demonstrated high drug content uniformity and nanoscale particle size (D₅₀ ≈ 185–200 nm). An approximately 8-fold increase in saturation solubility was observed compared with pure ezetimibe. BET analysis confirmed drug adsorption within the mesoporous silica network, evidenced by reduced surface area and pore volume. DSC and XRD analyses indicated predominant amorphization without polymorphic transitions. SEM and optical microscopy revealed porous, non-crystalline morphology consistent with molecular dispersion. In vitro dissolution studies showed negligible drug release in acidic medium, controlled release in intestinal pH, and rapid release at pH 7.4, with NM1 achieving >95% release within 60 minutes. Statistical evaluation confirmed the significantly enhanced dissolution performance of optimized formulations (p < 0.05).

Conclusion

The pH-sensitive solid nanomatrix system effectively enhances solubility, dissolution rate, and physical stability of ezetimibe through nanoconfinement within mesoporous silica and polymeric encapsulation. This scalable strategy offers a promising approach for improving the biopharmaceutical performance of poorly water-soluble drugs requiring intestinal-specific delivery.