Aleksovski Aleksandar, Van Bockstal Pieter-Jan, Roškar Robert, Sovány Tamás, Regdon Géza, De Beer Thomas, Vervaet Chris, Dreu Rok
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Eur J Pharm Sci. 2016 Jun 10;88:233-45. doi: 10.1016/j.ejps.2016.03.011. Epub 2016 Mar 12.
The aim of this study was to develop, evaluate and compare extended release mini-matrices based on metoprolol tartrate (MPT) and either glyceryl behenate (GB) or glyceryl palmitostearate (GPS). Mini-matrices were produced by three different techniques: hot melt extrusion, compression of melt granulates and prilling. Hot-melt extrusion and compression of granules obtained from melted material proved to be reliable, robust and reproducible techniques with aim of obtaining extended release matrices. Prilling tended to be susceptible to increased melt viscosity. Direct compression was not applicable for mini-matrix production due to poor powder flow. In general MPT release from all matrices was affected by its loading and the size of the units/particles. Processing of GB-MPT mixtures by different techniques did not lead to different drug release rates and patterns, while in case of GPS differently obtained matrices provided diverse MPT release outcomes. Matrices based on GB tended to have higher porosity compared to ones composed of GPS and thus most of the GB-based formulations showed faster drug delivery. FT-IR analysis revealed no interactions between primary components used for matrix production and Raman mapping outlined uniform MPT distribution throughout the units. DSC and X-ray studies revealed significant changes in the crystallinity of glycerides after storage under room conditions (GPS samples) and at increased temperature (GB and GPS samples), which was correlated to the changes seen in drug release rate and pattern after storage. Media composition in general tended to insignificantly affect GB matrices, while in case of GPS matrices increasing the pH and presence of biorelevant compounds induced faster drug release.
本研究的目的是开发、评估和比较基于酒石酸美托洛尔（MPT）与山嵛酸甘油酯（GB）或棕榈硬脂酸甘油酯（GPS）的缓释微型基质。微型基质通过三种不同技术制备：热熔挤出、熔融颗粒压制和造粒。事实证明，热熔挤出和由熔融材料获得的颗粒压制是可靠、稳健且可重复的技术，旨在获得缓释基质。造粒往往易受熔体粘度增加的影响。由于粉末流动性差，直接压片不适用于微型基质的生产。一般来说，所有基质中MPT的释放受其载药量和单位/颗粒大小的影响。用不同技术加工GB-MPT混合物不会导致不同的药物释放速率和模式，而对于GPS，不同方法获得的基质提供了不同的MPT释放结果。与由GPS组成的基质相比，基于GB的基质往往具有更高的孔隙率，因此大多数基于GB的制剂显示出更快的药物递送。傅里叶变换红外光谱（FT-IR）分析表明，用于基质生产的主要成分之间没有相互作用，拉曼映射显示MPT在整个单位中分布均匀。差示扫描量热法（DSC）和X射线研究表明，在室温条件下储存后（GPS样品）以及在升高温度下储存后（GB和GPS样品），甘油酯的结晶度发生了显著变化，这与储存后药物释放速率和模式的变化相关。一般来说，介质组成对GB基质的影响往往不显著，而对于GPS基质，提高pH值和存在生物相关化合物会导致更快的药物释放。
