Sustained release hGH microsphere formulation produced by a novel supercritical fluid technology: In vivo studies
Sustained release hGH microsphere formulation produced by a novel supercritical fluid technology: In vivo studies
复制标题
DOI：
10.1016/j.jconrel.2009.09.013
复制
发表时间：
2010-01-25
影响因子：
10.8
通讯作者：
Illum, L.
中科院分区：
文献类型：
--
作者：
Jordan, F.;Naylor, A.;Illum, L.
采用PLGA/PLA超临界流体工艺(CriticalMiX(TM)工艺)制备了hGH的新型缓释制剂，并将其制成微粒皮下注射。该工艺的基础是PLGA/PLA聚合物在暴露在超临界CO2中时液化，从而允许hGH在常温和无溶剂的情况下有效地混合到聚合物中。二氧化碳通过喷嘴减压从混合物中去除，产生含有hGH的微粒，并在旋风分离器中收集。最好的微球处方显示，最初的体外崩解率约为35%，缓释时间超过14天。在大鼠模型中，hGH的清除速度比其他动物模型更快，两种制剂在2-3天内持续释放，血药浓度维持在1-5 ng/ml，而可溶性hGH制剂在24小时内被清除。缓释制剂的突释量与每日剂量的hGH相似，血清hGH水平维持7天。从数据来看，如果继续采样，持续释放可能会持续长达14天。IGF-1结果显示，每日一次注射可溶hGH与两种缓释剂的血药浓度无显著差异。(C)2009爱思唯尔B.V.保留所有权利。
Novel sustained release formulations of hGH prepared by supercritical fluid Processing of PLGA/PLA (the CriticalMiX (TM) process) were produced in the form of microparticles for subcutaneous injection. The basis of the process is that PLGA/PLA polymers liquefy when exposed to supercritical CO2, thereby allowing the hGH to be mixed efficiently into the polymers at an ambient temperature and in the absence of solvents. The CO2 was removed from the mixture by depressurisation through a nozzle, resulting in the production of microparticles containing the hGH, which were collected in a cyclone. The best microparticle formulations showed an initial in vitro burst of around 35% and a sustained release over 14 days. When tested in the rat model, which displays a faster clearance rate of hGH than other animal models, two formulations showed prolonged release over 2-3 days with sustained plasma levels at 1-5 ng/ml whereas the soluble hGH formulation was cleared within 24 h. Two selected sustained release formulations were tested in cynomotgus monkeys and compared to a single injection of soluble hGH. The burst release from the sustained release formulations was similar in magnitude to a daily dose of hGH and serum hGH levels were maintained for a seven day period. It is probable from the data that the sustained release would have continued for up to 14 days if sampling had been continued. The IGF-1 results showed there was no significant difference between the levels obtained for once daily injection of soluble hGH and the two sustained release formulations. (C) 2009 Elsevier B.V. All rights reserved.