Structure and hydration properties of hydroxypropyl methylcellulose matrices containing naproxen and naproxen sodium

The present study was conducted to obtain a deeper insight into the mechani sm of drug release from HPMC matrices. The microstructure, mobility, intern al pH and the state of water within the gel layer of hydrated HPMC matrices (having different molecular weights) containing naproxen sodium (NS) and n aproxen (N) were studied using Electron Paramagnetic Resonance (EPR), Nucle ar Magnetic Resonance (NMR) and Differential Scanning Calorimetry (DSC) tec hniques. The study show that matrices composed of various viscosity grades of HPMC are characterized by similar microviscosity values in spite of the difference in their molecular weight. The NMR and DSC results led to the co nclusion that higher molecular weights of HPMC are characterized by higher water absorption capacity and higher swelling. Analysis of non-freezable wa ter in HPMC(K4M)-NS system revealed that addition of NS to solution increas ed the fraction of water bound to K4M + NS compared with the equivalent sol utions without NS. The: results suggest that the drug is participating in t he crystallization of water and leads to the formation of a three dimension al network structure that decreases the freedom of water in K4M + NS sample s. Calculation of the number of hydration shells showed that up to 2.2 laye rs are involved in HPMC-NS hydration compared to 1.5 layers for HPMC gel wi thout NS. This was explained based on the different water ordering in the g el induced by NS as results of its absorption to polymer surface. Microvisc osity values measured by EPR for K4M/N and K4M/NS hydrated matrices were fo und to be higher for K4M/N matrices, especially at initial stage of hydrati on. Mobile compartment calculations showed lower values for K4M/N compared with K4M/NS matrices. pH measurements by EPR revealed that incorporation of N to HPMC matrix led to lower internal pH value inside the hydrated tablet compared with NS. This behavior led to lower solubility of N which dictate s its surface erosion mechanism, compared with NS matrix that was character ized by higher internal pH value and higher drug solubility. These properti es of HPMC/NS increased chain hydration and stability, and led to drug rele ase by the diffusion mechanism. (C) 2000 Elsevier Science B.V. All rights r eserved.