The swelling properties of hydroxypropyl methyl cellulose loaded with tetracycline hydrochloride: magnetic resonance imaging study

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Abstract

Magnetic resonance imaging was used to study the behavior of the gel layer thickness in hydroxypropyl methyl cellulose (HPMC) matrices loaded with different amounts of soluble tetracycline hydrochloride. The time dependence of the diffusion front, effective T2, and proton-density analysis clearly indicates a Case II diffusion mechanism in the system composed of water solution of hydrochloric acid (pH=2) and HPMC. The solvent penetration front was used to describe the swelling properties as well as the integrity of the HPMC matrices. The results show that the tetracycline hydrochloride decreases the resistance of the HPMC network structure against the movement of solvent molecules. On the other hand the swelling properties of the matrix increase with the amount of drug in the matrix.

Introduction

Hydroxypropyl methyl cellulose (HPMC), the most common derivative of cellulose, has received much attention as a hydrophilic matrix used for the production of coated tablets and controlled release drugs. The gel layer formed on the glassy core of a polymer during the swelling is considered to be the controlling element of drug release kinetics. The kinetics of the swelling process of HPMC has been the subject of experimental studies by different methods. For example: by electron microscopy and NMR spectroscopy [1], [2]; an optical imaging technique [3]; a calorimetric technique [4]; ultrasound method [5]; gravimetrically [6] and by magnetic resonance imaging (MRI) [7], [8]. These studies demonstrate the influence of different parameters on the swelling properties of the HPMC matrix. Despite the interest in HPMC still some questions are necessary to answer in order to widely use this matrix in pharmacology.

In this work we were interested in the behavior of HPMC matrix loaded with tetracycline hydrochloride. Mostly we wanted to evaluate how the drug loading affected the swelling properties of the HPMC matrix into the water solution of hydrochloric acid (pH = 2). The pH value of the solvent was chosen to simulate the acidic condition of the human stomach. Tetracycline hydrochloride is one of the three most common drugs of the tetracycline group widely used as broad-spectrum antibiotics in medicine and therefore was taken as the model drug. As a method for our study we used MRI. This method is sensitive to the mobile protons on solvent molecules and as such is particularly useful for studying the interaction of the solvent with the polymer. To characterize the solvent ingress and its effects on structural and dynamical properties in the polymer, we acquired spatially resolved information such as proton spin-density and spin–spin relaxation times as a function of time.

Section snippets

Methods

MRI has been used to characterize the diffusion behavior of water solution of hydrochloric acid into HPMC and the swelling behavior of the polymer samples. The experiments were performed on a Bruker AVANCE 300 NMR spectrometer equipped with imaging facilities. The static B0 field of 7.05 T corresponds to a 1H resonance frequency of 300.23 MHz. A Bruker imaging probehead Micro 2.5 was used with a 15 mm birdcage coil. This probehead allows the applying of pulse gradients up to 1 T/m.

The progress of

Gel layer formation in polymer matrix

Drug release is primarily controlled by solvent penetration and drug diffusion across the gel layer formed by surface hydration of the polymer, in our case HPMC. Therefore, in this study we asked how the tetracycline HCl influences the diffusion of water into HPMC matrix and what the effect of drug concentration is on swelling and diffusion. For the sample consisting of 100% HPMC or HPMC with 25% or 33% polymer weight tetracycline hydrochloride we observed the formation of the gel layer as a

Conclusion

Magnetic resonance imaging can be used with great success to study the swelling properties of HPMC matrix. The spatially resolved proton-density images allow the measuring of the swelling and diffusion profiles. The solvent penetration front can be used to describe the swelling properties as well as the integrity of the HPMC matrix. The results show that the tetracycline hydrochloride plays an important role in the swelling properties of the HPMC polymer matrix. The resistance of the HPMC

Acknowledgements

We acknowledge financial support under Grant 4 P05F 010 19 from the Polish Committee for Scientific Research.

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