摘要
脂微球是一种以脂肪油为软基质并被磷脂包封的单分子层微粒体分散系。脂微球制剂产品有如下特点:脂微球注射液同传统的口服剂型和粉针剂型相比,药效更强,起效更迅速,持续时间更长。但由于PDF本身是一种酯结构,遇高温容易分解,做成脂微球注射剂后,灭菌工艺对其稳定性有极大的影响。
本文通过对脂微球灭菌工艺的研究,解决了PDF脂微球制剂在高温环境下制剂的不稳定性,减少活性物质PDF的分解,同时又保证脂微球制剂的无菌性。
通过研究不同温度、不同时间下PDF脂微球活性物质PDF含量降解度、PH值的变化、制剂外观、脂微球粒径的变化以及产品稳定性的考察,最终确定最佳灭菌时间和温度,使得PDF脂微球通过灭菌后达到灭菌的均一性和有效性,以及尽量减少PDF分解保证产品质量的稳定性。
本文研究结论:1.PDF脂微球注射液在灭菌条件115℃、20min;115℃、32min下,对产品外观、粒径、pH值、含量等质量控制指标变化最小。2.灭菌锅在空载和满载时热分布非常均匀,表明灭菌锅性能满足产品灭菌的需要,灭菌效果均匀性、有效性。在满载灭菌模式下,CⅡ区的安瓿温度较其他区域低,但也符合灭菌要求。3.PDF脂微球注射液在灭菌条件115℃、32min下,通过微生物(嗜热脂肪芽孢杆菌)负荷试验,满足GMP关于无菌制剂最小F0值8的要求。
Lipo microsphere is a monomolecular dispersing system. It's enveloped byphospholipid, and soybean oil inside. The average diameter of the lipo microsphere, LMis 200nm, and the average diameter of the lipo namo spheres,LN is 50nm. LM is greatdifference to oral and powder, LM have stronger drug effect, action faster, release longer.
The structure of the PDF is ester, which will be decomposed at high temperature. WhenPDF is dissolved in LM, the sterilization will take great effect on LM.The ampoule specification of the PDF is 20ml/per, in order to get the wellhomogeneity and efficacy of sterilization, and reduce the decompose of PDF which willcause less content than require, overheated water sterilization will satisfy all the requires.The medium of overheated water sterilization is overheated water. The product, which ispreparing for sterilization can be sterilized and heated by overheated water By the use ofoverheated water convection, the temperature of every product can be nearly same. Thesterile quality of product is getting higher and time is getting shorter. The overheatedwater sterilization has no dead angle, but it can be happen in steam sterilization, and italso avoids contamination of cooling water. The ampoule could not explode because theampoule is heated slowly and cooling down slowly. the sterilization temperature can beadjust between 60℃～127℃ ,and the ampoule leak check can use the color water whenthe color water get inside the vacuum sterilizer.
Through investigation for degradation,appearance, diameter and stability of PDFLM at different temperature , time, pH,present article determine the best sterile timeand temperature. After sterilizing, PDF LM will get the well homogeneity and efficacyand reduce the decompose of PDF to get the longer stability
引文
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