Compression behaviour of anhydrous and hydrate forms of sodium naproxen.

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.

Differences in the interaction between aryl propionic acid derivatives and poly(vinylpyrrolidone) K30: A multi-methodological approach.

The present work aims at the application of several methods to explain differences in the physical interaction of some aryl propionic acid derivatives (ibuprofen [IBP], ketoprofen [KET], flurbiprofen [FLU], naproxen [NAP], fenbufen [FEN]) with poly(vinylpyrrolidone) (PVP) K30, stored together at 298 +/- 0.5 K and 22% RH. X-ray powder diffractometry and (13)C-solid state NMR demonstrated that IBP was able to strongly interact with the polymer, while weak interaction was observed for KET, FLU, NAP, and the least for FEN. The interaction of comelted drug and PVP was studied by differential scanning calorimetry by applying the Gordon-Taylor equation, which revealed that small molar drug volumes may favour the drug diffusion through the PVP amorphous chains increasing the polymer free volume and decreasing the mixture T(g). The molecular docking study revealed that intermolecular energy is mainly due to the contribution of van der Waals energy component, causing the differences among the drugs, and is related to the drug-PVP surface contact area in the complex formed. Solid-state kinetic study demonstrated that IBP molecules are involved in a three-dimensional diffusion mechanism within the polymer favoured by its low molar volume that reduces molecular hindrance, and by the weakness of its crystal lattice, which facilitates crystallinity loss and stabilisation of the amorphous phase.