Lele B S, Hoffman A S
Bioengineering Department, University of Washington, Seattle 98195, USA.
J Biomater Sci Polym Ed. 2000;11(12):1319-31. doi: 10.1163/156856200744354.
We have developed a new mucoadhesive drug delivery formulation based on an ionic complex of partially neutralized poly(acrylic acid) (PAA) and a highly potent beta blocker drug, levobetaxolol x hydrochloride (LB x HCl), for use in the treatment of glaucoma. PAA was neutralized with sodium hydroxide to varying degrees of neutralization. Aqueous solutions containing concentrations of LB x HCl equivalent to the degree of PAA neutralization were added to the PAA solutions and formed insoluble complexes, which were isolated. The complex formation was followed by turbidimetric titration, and the complexes were characterized by IR and 1H NMR spectroscopy. Complexes were prepared with varying degrees of drug loading, such that the same PAA chain would have free -COOH groups for mucoadhesion along with ionic complexes of LB x H+ with COO- groups. Thin films of the complexes dissociated to release the drug by ion exchange with synthetic tear fluid. The films shrunk continuously during release of the drug and dissolved completely in 1 h. Solid inserts of these films could be useful as a mucoadhesive ophthalmic drug delivery system.
我们研发了一种基于部分中和的聚丙烯酸（PAA）与高效β受体阻滞剂药物盐酸左倍他洛尔（LB x HCl）的离子复合物的新型粘膜粘附给药制剂，用于治疗青光眼。用氢氧化钠将PAA中和至不同的中和度。将含有与PAA中和度相当浓度的LB x HCl的水溶液加入到PAA溶液中，形成不溶性复合物，然后将其分离出来。通过比浊滴定跟踪复合物的形成，并通过红外光谱和1H核磁共振光谱对复合物进行表征。制备了不同载药量的复合物，使得同一PAA链既有用于粘膜粘附的游离-COOH基团，又有LB x H⁺与-COO⁻基团形成的离子复合物。复合物薄膜通过与人工泪液进行离子交换而解离以释放药物。薄膜在药物释放过程中持续收缩，并在1小时内完全溶解。这些薄膜制成的固体插入物可作为一种粘膜粘附性眼科给药系统。
