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<p>Ticagrelor (TGL), a potent antiplatelet agent for acute coronary syndrome management, suffers from low aqueous solubility and poor oral bioavailability, limiting its clinical efficacy. This study aimed to develop and optimize a supersaturated self-nanoemulsifying drug delivery system (Super-SNEDDS) incorporating a polymeric precipitation inhibitor (PPI) to enhance dissolution, maintain supersaturation, and improve oral absorption. Solubility and emulsification studies identified Capmul MCM (oil), Acrysol K150 (surfactant), and Transcutol HP (co-surfactant) as suitable excipients, with ternary phase diagrams guiding ratio optimization. A simplex centroid design was employed to refine formulation variables, targeting reductions in globule size, increased saturated solubility, and minimized precipitation. Supersaturated formulations containing polyvinylpyrrolidone K30 (PVP K30) at 3.0%, 6.0%, and 9.0% w/w were evaluated to suppress drug precipitation. The optimized Super-SNEDDS (10% Capmul MCM, 55% Acrysol K150, 35% Transcutol HP) with 6% w/w PVP K30 exhibited rapid self-emulsification (18&#xa0;s), nanosized droplets (13.44&#xa0;nm, PDI 0.226), high drug content (99.3 ± 0.47%), excellent thermal and dilution stability, and negligible precipitation. In vitro dissolution studies demonstrated &gt; 98% TGL release within 120&#xa0;min across varied pH conditions. In vivo pharmacokinetic studies in rats revealed a 2.17-fold enhancement in oral bioavailability over conventional SNEDDS and a 6.98-fold increase compared to plain suspension. Post-encapsulation stability studies confirmed the physicochemical integrity of the formulation in HPMC capsules. The bioavailability enhancement was attributed to increased surface area, stabilized supersaturation, and improved absorption. These results underscore the potential of precipitation-inhibited Super-SNEDDS as a scalable, patient-compliant strategy for enhancing the oral delivery of poorly soluble drugs like TGL in cardiovascular therapy.</p> Graphical Abstract <p></p>

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Precipitation Inhibitor–Stabilized Supersaturated SNEDDS of Ticagrelor: Design, Optimization, and Pharmacokinetic Study

  • 期刊论文

  • 发表日期：

    2025年8月30日

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  • Mariyambibi A. Mandarawala,
  • Ashok N. Mahajan,
  • Shaileshkumar K. Koradia,
  • Moinuddin M. Soniwala

摘要

Ticagrelor (TGL), a potent antiplatelet agent for acute coronary syndrome management, suffers from low aqueous solubility and poor oral bioavailability, limiting its clinical efficacy. This study aimed to develop and optimize a supersaturated self-nanoemulsifying drug delivery system (Super-SNEDDS) incorporating a polymeric precipitation inhibitor (PPI) to enhance dissolution, maintain supersaturation, and improve oral absorption. Solubility and emulsification studies identified Capmul MCM (oil), Acrysol K150 (surfactant), and Transcutol HP (co-surfactant) as suitable excipients, with ternary phase diagrams guiding ratio optimization. A simplex centroid design was employed to refine formulation variables, targeting reductions in globule size, increased saturated solubility, and minimized precipitation. Supersaturated formulations containing polyvinylpyrrolidone K30 (PVP K30) at 3.0%, 6.0%, and 9.0% w/w were evaluated to suppress drug precipitation. The optimized Super-SNEDDS (10% Capmul MCM, 55% Acrysol K150, 35% Transcutol HP) with 6% w/w PVP K30 exhibited rapid self-emulsification (18 s), nanosized droplets (13.44 nm, PDI 0.226), high drug content (99.3 ± 0.47%), excellent thermal and dilution stability, and negligible precipitation. In vitro dissolution studies demonstrated > 98% TGL release within 120 min across varied pH conditions. In vivo pharmacokinetic studies in rats revealed a 2.17-fold enhancement in oral bioavailability over conventional SNEDDS and a 6.98-fold increase compared to plain suspension. Post-encapsulation stability studies confirmed the physicochemical integrity of the formulation in HPMC capsules. The bioavailability enhancement was attributed to increased surface area, stabilized supersaturation, and improved absorption. These results underscore the potential of precipitation-inhibited Super-SNEDDS as a scalable, patient-compliant strategy for enhancing the oral delivery of poorly soluble drugs like TGL in cardiovascular therapy.

Graphical Abstract