Dipartimento di Scienze Farmaceutiche P. Pratesi, Università degli Studi di Milano, Milano, Italy.
Eur J Pharm Biopharm. 2010 Jun;75(2):291-6. doi: 10.1016/j.ejpb.2010.03.007. Epub 2010 Mar 18.
A delivery device intended for the prolonged release of antimicrobial agents, able to enhance the stability profile of liquid/semi-solid cosmetic/pharmaceutical products for topical application, was proposed in the present study. With the aid of a simulation program based on compartment models, the relevant kinetic and formulation parameters were defined using dehydroacetic acid sodium salt (DHA.Na, Prevan) as the model preservative. Indeed, the overall DHA.Na degradation rate is increased in the presence of formaldehyde releasers that are often employed as co-preservatives. Inert matrices (3 g weight and 18 mm diameter) based on high-density polyethylene (HDPE), possibly consistent with the design of an active packaging meant for preservative delivery, were prepared by hot-melt extrusion. Units with satisfactory physical-technological properties could be obtained up to 50%w/w loads of antimicrobial agent. In an attempt to modify the relevant Fickian release profiles by varying the area exposed to the medium, matrix systems coated with an impermeable film except for one base (CMs) or for the inner surface of a central drilled hole (PCMs) were investigated. On the basis of the n exponent of power equation and the outcome of linear fitting, PCMs were proven able to yield the zero-order release behaviour needed to ensure constant DHA.Na levels over a predetermined time period, as indicated by the simulation process.
本研究提出了一种用于延长释放抗菌剂的给药装置，该装置能够提高用于局部应用的液体/半固体化妆品/药物产品的稳定性。借助基于室模型的模拟程序，使用脱氢乙酸钠（DHA.Na，Prevan）作为模型防腐剂来定义相关的动力学和配方参数。事实上，在通常用作共防腐剂的甲醛释放剂存在下，整体 DHA.Na 降解速率会增加。基于高密度聚乙烯（HDPE）的惰性基质（3 克重量和 18 毫米直径），可能符合旨在提供防腐剂输送的活性包装的设计，通过热熔挤出制备。可以获得具有令人满意的物理-技术性能的单位，最高可达 50%w/w 的抗菌剂负载。为了通过改变暴露于介质的面积来改变相关的菲克扩散释放曲线，研究了除一个底座外均涂有不渗透膜的基质系统（CMs）或中央钻孔的内表面涂有不渗透膜的基质系统（PCMs）。基于幂方程的 n 指数和线性拟合的结果，PCMs 被证明能够产生零级释放行为，从而在预定时间段内确保 DHA.Na 水平保持恒定，这是模拟过程所表明的。
