Lee P I
J Pharm Sci. 1984 Oct;73(10):1344-7. doi: 10.1002/jps.2600731004.
A novel approach to zero-order drug delivery from glassy hydrogel matrices via an immobilized, sigmoidal, initial drug distribution has been developed. The method utilizes a controlled-extraction process on initially dry, drug-loaded hydrogels to generate an inflection-point-containing drug concentration profile followed by a vacuum freeze-drying step to rapidly remove the swelling solvent and immobilize in situ a nonuniform drug distribution. The drug release from such a system generally exhibits typical zero-order characteristics similar to that of a membrane-reservoir device. However, a saturated reservoir of active ingredient as in the membrane-reservoir device is not required because the constant release is achieved via an initially nonuniform concentration distribution instead of the constant activity in a reservoir. The applicability of the present concept and process has been demonstrated experimentally with the release of oxprenolol hydrochloride from hydrogel beads based on 2-hydroxyethyl methacrylate polymerized with a polymeric cross-linking agent.
通过固定化的S形初始药物分布从玻璃态水凝胶基质中进行零级药物递送的新方法已经被开发出来。该方法利用对初始干燥的载药水凝胶进行控制萃取过程，以产生包含拐点的药物浓度分布，随后进行真空冷冻干燥步骤，以快速去除溶胀溶剂并原位固定不均匀的药物分布。从这样一个系统中释放药物通常表现出类似于膜储库装置的典型零级特征。然而，不需要像膜储库装置那样有活性成分的饱和储库，因为恒定释放是通过初始不均匀的浓度分布而不是储库中的恒定活性来实现的。基于甲基丙烯酸2-羟乙酯与聚合物交联剂聚合而成的水凝胶珠中盐酸氧烯洛尔的释放，通过实验证明了本概念和方法的适用性。
