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Objective <p>This study developed a novel pH-responsive polyelectrolyte complex hydrogel system for oral delivery of rosuvastatin, a widely prescribed statin for cholesterol management and cardiovascular risk reduction which is classified as a BCS Class II drug due to its poor aqueous solubility and limited oral bioavailability.</p> Methods <p>A series of eleven formulations (F1–F11) were prepared through free radical polymerization based on a rationally designed ternary polymeric matrix of chitosan, xanthan gum, and carboxymethyl cellulose sodium, crosslinked with acrylic acid and N, N′-methylene bisacrylamide (MBA).</p> Results <p>The optimized hydrogel (F10) exhibited a high entrapment efficiency (94.21 ± 1.35%) driven by electrostatic interactions between chitosan’s amine groups and rosuvastatin’s sulfonate moieties and effectively overcame the intrinsic solubility barrier of rosuvastatin—demonstrated by &gt; 90% cumulative drug release at intestinal pH (7.4). Swelling studies under simulated gastrointestinal conditions showed pH-responsive behavior, with significantly higher swelling at pH 7.4 compared to pH 1.2 (<i>p</i> &lt; 0.01), facilitating intestinal-specific drug release. In vitro drug release at pH 7.4 was more than 90% for the optimized formulation, following anomalous (non-Fickian) kinetics (Higuchi R² &gt; 0.97; Korsmeyer–Peppas <i>n</i> = 0.78–0.83), which suggested a combination of diffusion and polymer relaxation mechanisms. The Weibull model analysis (parameters α, β) further confirmed the anomalous release mechanism. Physicochemical characterization revealed strong drug–polymer compatibility (FTIR), thermal stability up to 200&#xa0;°C (DSC/TGA), and porous morphology. In vivo acute oral toxicity studies (2&#xa0;g/kg in mice) demonstrated the hydrogel’s biosafety, with no significant hematological or histopathological abnormalities (<i>p</i> &gt; 0.05).</p> Conclusion <p>These findings establish a pharmaceutically robust hydrogel platform that addresses the key biopharmaceutical challenges of BCS Class II drugs particularly solubility and absorption barriers—through rational polymer engineering. While in vivo pharmacokinetic validation is required for definitive bioavailability claims, the demonstrated pH-responsive swelling and release behavior, high drug loading, and acute biosafety provide a strong mechanistic foundation for further translational development.</p>

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pH Responsive Polymeric Blend for Enhanced Solubility, Controlled Release, and Therapeutic Optimization of Rosuvastatin

  • 期刊论文

  • 发表日期：

    2026年2月12日

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  • Asmaa Jabeen,
  • Nadia Shamshad Malik,
  • Ume Ruqia Tulain,
  • Alia Erum,
  • Syed Faisal Badshah,
  • Nitasha Gohar,
  • Sajjad Hussain,
  • Maira Anwar,
  • Alina Javaid,
  • Sohail Akram

摘要

Objective

This study developed a novel pH-responsive polyelectrolyte complex hydrogel system for oral delivery of rosuvastatin, a widely prescribed statin for cholesterol management and cardiovascular risk reduction which is classified as a BCS Class II drug due to its poor aqueous solubility and limited oral bioavailability.

Methods

A series of eleven formulations (F1–F11) were prepared through free radical polymerization based on a rationally designed ternary polymeric matrix of chitosan, xanthan gum, and carboxymethyl cellulose sodium, crosslinked with acrylic acid and N, N′-methylene bisacrylamide (MBA).

Results

The optimized hydrogel (F10) exhibited a high entrapment efficiency (94.21 ± 1.35%) driven by electrostatic interactions between chitosan’s amine groups and rosuvastatin’s sulfonate moieties and effectively overcame the intrinsic solubility barrier of rosuvastatin—demonstrated by > 90% cumulative drug release at intestinal pH (7.4). Swelling studies under simulated gastrointestinal conditions showed pH-responsive behavior, with significantly higher swelling at pH 7.4 compared to pH 1.2 (p < 0.01), facilitating intestinal-specific drug release. In vitro drug release at pH 7.4 was more than 90% for the optimized formulation, following anomalous (non-Fickian) kinetics (Higuchi R² > 0.97; Korsmeyer–Peppas n = 0.78–0.83), which suggested a combination of diffusion and polymer relaxation mechanisms. The Weibull model analysis (parameters α, β) further confirmed the anomalous release mechanism. Physicochemical characterization revealed strong drug–polymer compatibility (FTIR), thermal stability up to 200 °C (DSC/TGA), and porous morphology. In vivo acute oral toxicity studies (2 g/kg in mice) demonstrated the hydrogel’s biosafety, with no significant hematological or histopathological abnormalities (p > 0.05).

Conclusion

These findings establish a pharmaceutically robust hydrogel platform that addresses the key biopharmaceutical challenges of BCS Class II drugs particularly solubility and absorption barriers—through rational polymer engineering. While in vivo pharmacokinetic validation is required for definitive bioavailability claims, the demonstrated pH-responsive swelling and release behavior, high drug loading, and acute biosafety provide a strong mechanistic foundation for further translational development.