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<p>The anti-glaucoma drug betaxolol hydrochloride (BH) exhibits poor ocular bioavailability due to limited corneal permeability, rapid precorneal loss, short retention time, and lacrimal drainage when administered conventionally. In the present study, a solid–liquid lipid-based nano-ocular carrier (NC) of BH was developed to modulate transcorneal permeability and improve intraocular efficacy. Initially, solid and liquid lipid excipients were screened on the basis of BH solubility, followed by ternary phase behavior analysis in normal saline to identify a one-phase region (OPR). It was processed at a controlled temperature, enabling the transformation of the nano-emulsified system into lipid-based NCs. NCs were fabricated from glyceryl monostearate (X<sub>1</sub>), tocopherol acetate (X<sub>2</sub>), and a Tween20/Transcutol mixture (X<sub>3</sub>). A Box–Behnken design (BBD) was employed to evaluate the effects of formulation variables on particle size (Y<sub>1</sub>), entrapment efficiency (Y<sub>2</sub>), and polydispersity index (Y<sub>3</sub>). Optimized formulations (NC-9, NC-11, and NC-15) exhibited particle sizes in the range of 250–300&#xa0;nm, high drug entrapment (90%), and sustained drug release following zero-order kinetics. Selected NCs were evaluated for transcorneal permeability using excised goat cornea and for intraocular pressure (IOP)-lowering efficacy in a rabbit model. Optimized formulation NC-9 demonstrated significantly enhanced transcorneal permeation compared to BH solution (p &lt; 0.001) and produced a greater reduction in IOP, reflected by an increased AUC<sub>IOP</sub>. Stability studies conducted as per ICH guidelines confirmed formulation stability over six months. Moreover, NC-9 was non-hemolytic (0.8 ± 0.2%) compared with slightly hemolytic BH solution (3.33 ± 0.69%), indicating improved biocompatibility. Overall, the developed lipid-based NC system significantly improved ocular retention, permeability, and therapeutic efficacy of BH compared to conventional eye drops.</p>

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Quality-by-design-based fabrication of betaxolol hydrochloride-loaded nano-ocular carrier via ternary phase mapping of solid/liquid lipids and BBD modeling for enhanced transcorneal flux and IOP-lowering effect

  • 期刊论文

  • 发表日期：

    2026年5月15日

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  • Nishant Kumar,
  • Anoop Kumar,
  • Sokindra Kumar

摘要

The anti-glaucoma drug betaxolol hydrochloride (BH) exhibits poor ocular bioavailability due to limited corneal permeability, rapid precorneal loss, short retention time, and lacrimal drainage when administered conventionally. In the present study, a solid–liquid lipid-based nano-ocular carrier (NC) of BH was developed to modulate transcorneal permeability and improve intraocular efficacy. Initially, solid and liquid lipid excipients were screened on the basis of BH solubility, followed by ternary phase behavior analysis in normal saline to identify a one-phase region (OPR). It was processed at a controlled temperature, enabling the transformation of the nano-emulsified system into lipid-based NCs. NCs were fabricated from glyceryl monostearate (X1), tocopherol acetate (X2), and a Tween20/Transcutol mixture (X3). A Box–Behnken design (BBD) was employed to evaluate the effects of formulation variables on particle size (Y1), entrapment efficiency (Y2), and polydispersity index (Y3). Optimized formulations (NC-9, NC-11, and NC-15) exhibited particle sizes in the range of 250–300 nm, high drug entrapment (90%), and sustained drug release following zero-order kinetics. Selected NCs were evaluated for transcorneal permeability using excised goat cornea and for intraocular pressure (IOP)-lowering efficacy in a rabbit model. Optimized formulation NC-9 demonstrated significantly enhanced transcorneal permeation compared to BH solution (p < 0.001) and produced a greater reduction in IOP, reflected by an increased AUCIOP. Stability studies conducted as per ICH guidelines confirmed formulation stability over six months. Moreover, NC-9 was non-hemolytic (0.8 ± 0.2%) compared with slightly hemolytic BH solution (3.33 ± 0.69%), indicating improved biocompatibility. Overall, the developed lipid-based NC system significantly improved ocular retention, permeability, and therapeutic efficacy of BH compared to conventional eye drops.