Department of Pharmacy, University of Tirana, Albania.
Int J Pharm. 2010 May 10;390(2):142-9. doi: 10.1016/j.ijpharm.2010.01.036. Epub 2010 Feb 1.
The aim of the present work was to investigate the technological properties and the compression behaviour of the anhydrous and hydrate solid forms of sodium naproxen. Among the hydrates, the following forms were studied: the monohydrate (MSN), obtained by dehydrating a dihydrated form (DSN) in each turn obtained by exposing the anhydrous form at 55% RH; a dihydrated form (CSN) obtained by crystallizing sodium naproxen from water, the tetrahydrated form (TSN) obtained by exposing the anhydrous form at 75% RH. The physico-chemical (crystalline form and water content), the micromeritic (crystal morphology and particle size) and the mechanical properties (Carr's index, apparent particle density, compression behaviour, elastic recovery and strength of compact) were evaluated. We made every effort to reduce differences in crystal habit, particle size and distribution, and amount of absorbed water among the samples, so that the only factors affecting their technological behaviour would be the degree of hydration and the crystalline structure. This study demonstrates a correlation between the compression behaviour and the water molecules present in the crystalline structures. The sites where water molecules are accommodated in the crystalline structure behave like weak points where the crystalline lattice yields under compression. The crystal deformability is proportional to the number of water molecules in these sites; the higher the water content, the higher the deformability, because the densification behaviour changes from a predominantly elastic deformation to a plastic behaviour. The deformability is responsible for a higher densification tendency that favours larger interparticle bonding areas that may explain the better tabletability of TSN and CSN.
本工作旨在研究无水和水合固体形式的萘普生钠的工艺性能和压缩行为。在所研究的水合物中,研究了以下形式:一水合物(MSN),通过在每次暴露于 55%RH 的无水形式中脱水而获得;通过从水中结晶萘普生获得的二水合物(CSN),通过在 75%RH 下暴露于无水形式获得的四水合物(TSN)。评估了物理化学性质(结晶形式和含水量)、微粉学性质(晶体形态和粒径)和机械性能(卡尔指数、表观颗粒密度、压缩行为、弹性恢复和压缩强度)。我们尽一切努力减少样品之间晶体习性、粒径和分布以及吸收水分的差异,以便唯一影响其工艺性能的因素是水合程度和晶体结构。这项研究表明,压缩行为与晶体结构中存在的水分子之间存在相关性。水分子在晶体结构中容纳的位置表现为晶体格子在压缩下屈服的弱点。晶体的可变形性与这些位置中水分子的数量成正比;水含量越高,可变形性越高,因为致密化行为从主要弹性变形转变为塑性行为。可变形性导致更高的致密化趋势,有利于更大的颗粒间结合面积,这可以解释 TSN 和 CSN 更好的可压性。