Gel Strength of Hydrophilic Matrix Tablets in Terms of In Vitro Robustness

Seyedreza Goldoozian,Roland Bodmeier,Andriy Dashevskiy,Valentyn Mohylyuk

doi:10.1007/s11095-021-03068-y

Seyedreza Goldoozian, Roland Bodmeier + Show 2 more

Open Access

https://doi.org/10.1007/s11095-021-03068-y

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Abstract

PurposeThe purpose of this study was to correlate the gel strength of swollen matrix tablets with their in vitro robustness against agitation intensity and applied mechanical forces. Five commercial products, i.e. Glucophage®, Alfuzosin®, Tromphyllin®, Preductal® MR and Quetiapin® formulated as water-soluble/erodible matrix tablets were investigated.MethodsEffect of agitation speed (50–150 rpm) on drug release, hydration/erosion and gel strength was investigated using USP paddle apparatus II. The gel strength of matrix tablets during dissolution at different conditions was characterized by a texture analyzer.ResultsCommercial tablets formulated with HPMC of higher viscosity, such as K15M or K100M, demonstrated the gel strength in swollen state >0.02 MPa. In this case, the release mechanism was predominantly diffusional and, therefore, not affected by stirring speed and mechanical stress. In contrast, the Quetiapin® matrix tablet, formulated with HPMC K 4 M in amount of approx. 25%, demonstrated the gel strength dropped below 0.02 MPa after 6 h of release. In this case, the drug was predominantly released via erosional mechanism and very susceptible to stirring speed.ConclusionSufficient gel strength of swollen tablets is an important prerequisite for unchanged in vitro performance in consideration of mechanical stress.

Highlights

Hydrophilic matrix tablets remain an important approach to achieve controlled oral drug release. They are formulated using non-cross-linked, water-swellable polymers, e.g. hydroxypropyl methylcellulose (HPMC), that swell rapidly enough to form a continuous ‘gel layer’ surrounding the dry core in order to control the rate of drug release during passage of the matrix through the gastrointestinal (GI) tract
The behavior of the tablet upon contact with dissolution medium in vitro or gastrointestinal fluid in vivo strongly depends on type and amount of HPMC
Visual observation of Quetiapin® tablets after release at paddle speed of 50 rpm showed that the residue of the HPMC matrix tablet was a small soft gel mass which fell apart when touched

Summary

Introduction

Hydrophilic matrix tablets remain an important approach to achieve controlled oral drug release. They are formulated using non-cross-linked, water-swellable polymers, e.g. hydroxypropyl methylcellulose (HPMC), that swell rapidly enough to form a continuous ‘gel layer’ surrounding the dry core in order to control the rate of drug release during passage of the matrix through the gastrointestinal (GI) tract. Considering the matrix, the surface of the tablet swells, and an outer gel layer is formed associated with polymer chains relaxation [2,3]. Gradual matrix hydration toward the core results in formation of a polymer concentration gradient while three zones, namely, outer gel layer, swollen glassy layer and dry core can be identified. Drug dissolution in the gel and polymer relaxation affect the relative movement of the fronts and, the distance between swelling and diffusion fronts [4,5]

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