Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethylcellulose Matrix Tablets In Situ–Is it Possible to Detect Phenomena Related to Drug Dissolution Within the Hydrated Matrices?

Piotr Kulinowski,Krzysztof Jasiński,Anna Młynarczyk,Przemysław Dorożyński,Bogusław Tomanek,Marco L H Gruwel,Władysław P Węglarz,Przemysław Talik

doi:10.1007/s11095-014-1334-2

Abstract

PurposeSo far, the hydrated part of the HPMC matrix has commonly been denoted as a “gel” or “pseudogel” layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena.MethodsMultiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals.ResultsTwo components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external “gel-like” layer.ConclusionsWe have introduced a new paradigm in the characterization of hydrating matrices using 1H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

Highlights

Studies on the behavior of controlled release (CR) hydroxypropylmethylcellulose (HPMC) matrix systems emerged in the late 1960’s [1]
We have introduced a new paradigm in the characterization of hydrating matrices using 1H magnetic resonance imaging (MRI) methods
This paper extends the application of previously developed methodology based on spatially resolved, magnetic resonance microscopy (T2 relaxometry) to HPMC matrix loaded with drugs of different solubility

Summary

Introduction

Studies on the behavior of controlled release (CR) hydroxypropylmethylcellulose (HPMC) matrix systems emerged in the late 1960’s [1]. In the mid 90’s the spatial characteristics of the drug loaded matrix during hydration was proposed [2]. The borders between the particular zones were defined as fronts–an erosion front separating the hydrogel from the surrounding solution, a swelling front identified between the hydrated glassy polymer and dry glassy polymer and diffusion front between solid and dissolved drug in the matrix. This early approach to understanding the structure of swelling matrices was based on simple photo imaging of hydrated tablets, where water penetration was restricted by placing the tablet between two glass plates. The basic concept of a three front model for the swollen tablet is recognized as a gold standard to describe the structure of hydrated CR matrix systems

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