苄达赖氨酸离子敏感型眼用原位凝胶的研究

Prepration and Evaluation of Ion-sensitive Ophthalmic in Situ Gel Containing Bendazac Lysine

目的制备苄达赖氨酸离子敏感型眼用原位凝胶(BDZL-ISG),对其流变学特征、体外释放性和离体角膜渗透性等进行评价,并研究药物在兔眼房水初步的药动学特征。方法利用黏度和胶凝能力对处方进行单因素考察,筛选出最优处方;以市售滴眼液或溶液剂为对照,采用透析膜法考察该处方的体外释放性;采用Franz扩散池对该处方进行离体角膜渗透研究。并采用微透析取样技术初步研究了药物在兔眼房水中的药动学特征。结果该处方具有剪切稀释特性,相比于对照组缓释效果明显;离体角膜渗透研究结果表明,该处方角膜累积渗透率与市售处方无显著性差异。房水药动学结果表明,苄达赖氨酸离子敏感型眼用原位凝胶组给药后ρ_(max)(13.25μg·L^(-1))为市售组的2.38倍,AUC0-t为市售组的2.2倍,眼部生物利用度显著提高。结论苄达赖氨酸离子敏感型眼用原位凝胶缓释效果明显,能有效提高药物的眼部生物利用度,有望成为治疗白内障的新剂型。

OBJECTIVE To prepare ion-sensitive ophthalmic in situ gel containing bendazac lysine（BDZL-ISG） and preliminarily study its rheological behavior,in vitro drug release,corneal permeation,and pharmacokinetics in rabbit aqueous humor.METHODS Single factor investigation was carried out to optimize the formulation,taking viscosity and gelling capacity as evaluation indices.Using aqueous solution or eye drops as control,the in vitro release of the formulation was evaluated by dialysis membrane method.Then,the corneal permeation experiment of the optimum formulation was carried out with Franz diffusion cell.The pharmacokinetics of BDZL-ISG in rabbit aqueous humor was preliminarily studied by microdialysis.RESULTS Compared with the control group,the optimum formulation had shear thinning behavior and significant sustained release effect.There was no significant difference in the corneal permeation between the two groups.The results of pharmacokinetic study showed that ρmax（13.25 μg·L^（-1）） and AUC0-tof BZDL-ISG were 2.38 and 2.2 times higher than those of BDZL eye drops respectively,which suggested that the ocular bioavailability of BDZL was greatly enhanced by the optimum in situ gel formulation.CONCLUSION With significant sustained release effect,the ion-sensitive ophthalmic in situ gel will become a promising alterative formulation for bendazac lysine for treatment of cataracts.