Studies of the internal flow process in polymers by 1H NMR microscopy at 500 MHz

doi:10.1016/S0168-3659(98)00069-8

Journal of Controlled Release

Volume 56, Issues 1–3, 4 December 1998, Pages 95-104

https://doi.org/10.1016/S0168-3659(98)00069-8 Get rights and content

Abstract

Nuclear Magnetic Resonance (NMR) microscopy was used to study the dynamics and diffusion of the internal water flow in erodible Hydroxypropylmethylcellulose (HPMC) and Polyvinylalcohol (PVA) polymers of pharmaceutical interest. Polymers in the form of tablets were hydrated at 37°C continuously and monitored at regular intervals with a 500 MHz NMR microscope. The diffusion and spin–spin relaxation time (T₂)-weighted images revealed that the gel layer was strongly attached to the core of the tablet in both HPMC and PVA polymers. Spatial distribution of self diffusion coefficients (SDCs) and T₂ of the hydrating polymers were calculated from NMR microscopic images.

Introduction

In recent years considerable efforts have been made to understand the mechanisms of drug release from polymer matrices. Consequently, the use of hydrophilic polymer tablets is increasing due to the possibility of controlled drug delivery in the human body. One of the important mechanisms that govern the release of drugs is the water penetration (hydration) into a dry hydrophilic matrix. Up on hydration, the hydrophilic matrix swells and eventually erodes at the surface. The hydrated surface forms a viscous mucilaginous gel layer which retards further uptake of water, thus acting as a diffusion barrier. In spite of its major role, not many studies on the surface gel have been performed. Hence, it is of interest to study the diffusion behaviour of water molecules in polymer gels in order to optimise and develop controlled release formulations of such systems. Some attempts have been made in recent years to study the hydrating polymers by NMR (Nuclear Magnetic Resonance) imaging and microscopy. The water penetration rate in hydrophilic polymer matrix capsule plugs was measured with NMR imaging by Ashraf et al. [1]. Gao and Fagerness [2]determined drug and water diffusivity using pulsed-field gradient spin-echo NMR. However, their diffusion studies dealt with the bulk matter and not as a function of the spatial and temporal coordinates. The use of pulsed field gradients coupled with NMR imaging enables precise determination of the spatial distribution of self diffusion coefficients (SDCs) in NMR images. Similarly, spin–spin relaxation time (T₂)-weighted images enable calculation of the spatial distribution of the T₂ in the NMR images. Using these NMR imaging methods, Rajabi et al. 3, 4, 5studied the water mobility and spatial distribution of the diffusion coefficient in the gel layer of HPMC tablets. SDC is a measure of transport due to the thermal energy (also known as Brownian motion) of molecules in the absence of a chemical concentration gradient whereas T₂ is a measure of the translational and rotational freedom of the molecule. Hence, both SDC and T₂ strongly depend on the mobility of water.

NMR microscopic imaging provides a noninvasive and continuous way to measure the unsaturated water in polymer materials as an alternative to invasive gravimetric sampling and optical microscopy. NMR image contrast depends on the differences in the environments of the nuclei and a number of chemical and physical effects influence these environments. Careful interpretation of the NMR image contrast gives information about these effects along with their spatial dependence. Variations in the echo times and repetition times of pulse sequences produce the T₂ and T₁-weighting in spin-echo imaging methods. Diffusion-weighted imaging and calculation of the spatial distribution of the SDCs are possible with the Stimulated-echo imaging method interlaced with pulsed field gradients. In addition to this, one can vary the external physical and chemical parameters such as the temperature and composition of the media and study the system under investigation.

The aim of this study was to investigate the hydration of two erodible polymer systems (hydroxypropylmethylcellulose and polyvinylalcohol in the form of tablets) by NMR microscopy. NMR microscopic imaging was used to monitor the hydration of the polymers at 37°C at regular intervals. The spatial distribution of T₂ was calculated from T₂-weighted spin-echo images and self diffusion coefficients were calculated from diffusion-weighted images.

Section snippets

Polymers

Hydroxypropylmethylcellulose (HPMC), Metolose 60SH50 and 60SH10000 were supplied by Shin-Etsu. Polyvinylalcohol (PVA) 22 000 and 72 000 were supplied by Fluka AG. HPMC and PVA polymer matrices were prepared by making cylindrical tablets in a Diaf Excenter Press. The substances were used as received and the diameter of the tablets was 6 mm and the length of 8 mm was used to minimise the edge effects. The tablet hardness was approximately 13 kp.

NMR microscopy

NMR microscopy experiments were performed on a

Results and discussion

NMR Microscopic images of tablets showed not only the general shape of the tablet but also irregularities in both the radial and axial directions. The fine structural features of gel were also clearly visible in the images, together with susceptibility artifacts due to the air bubbles.

The stimulated-echo diffusion-weighting method was used for diffusion studies in this investigation instead of spin-echo imaging with a pulsed field gradient 3, 4, 5. A problem associated with the use of spin-echo

Conclusions

Spatial spin–spin relaxation times and diffusion coefficients were determined for hydrating HPMC and PVA polymer tablets. From these parameters, water mobility in the gel formed due to the hydration was estimated. The gel formed due to PVA hydration restricts water more than the gel of HPMC polymers. Minor variations in the pattern of hydration due to the differences in molecular weight and matrices of polymers can be measured with NMR microscopic imaging in both solvating and swelling polymer

Acknowledgements

This project was supported by Astra-Hässle AB, Lundberg foundation, Wallenberg foundation and Swedish Medical Research Council.

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Studies of the internal flow process in polymers by 1H NMR microscopy at 500 MHz

Abstract

Introduction

Section snippets

Polymers

NMR microscopy

Results and discussion

Conclusions

Acknowledgements

J. Contr. Rel.

Magn. Reson. Imag.

J. Colloid Interface Sci.

J. Magn. Reson.

J. Magn. Reson.

Studies of the internal flow process in polymers by ¹H NMR microscopy at 500 MHz