Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul;38(7):1297-1306.
doi: 10.1007/s11095-021-03068-y. Epub 2021 Jun 21.

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

Seyedreza Goldoozian  1 , Valentyn Mohylyuk  1   2 , Andriy Dashevskiy  3 , Roland Bodmeier  1
Affiliations

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

Seyedreza Goldoozian et al. Pharm Res. 2021 Jul.

Abstract

Purpose: The 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.

Methods: Effect 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.

Results: Commercial 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.

Conclusion: Sufficient gel strength of swollen tablets is an important prerequisite for unchanged in vitro performance in consideration of mechanical stress.

Keywords: HPMC; gel strength; matrix tablets; mechanical stress; release robustness.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic representation of gel strength determination upon hydration.
Fig. 2
Fig. 2
Dissolution profiles for different products at different agitation speed: (A) Glucophage®, (B) Alfuzosin®, (C) Tromphyllin®, (D) Preductal®, (E) Quetiapin®.
Fig. 3
Fig. 3
Schematic representation of gel strength profile within swellable matrix tablet.
Fig. 4
Fig. 4
Gel strength profiles of investigated products by texture analyzer in different swelling time (in pH 6.8 with paddle apparatus at 50 rpm: (A) Glucophage®, (B) Alfuzosin®, (C) Tromphyllin®, (D) Preductal®, (E) Quetiapin®.
Fig. 5
Fig. 5
Gel strength (MPa) at gel-solution interface tested in phosphate buffer solution pH 6.8 at paddle speed of 50 rpm.
Fig. 6
Fig. 6
Effect of stirring speed at 50 rpm vs. 150 rpm on gel strength at gel-solution interface (MPa) in different swelling times: (A) Glucophage®, (B) Alfuzosin®, (C) Preductal®, (D) Quetiapin®. Commercial product Tromphyllin® was not available for this experiment.
Fig. 7
Fig. 7
Hydration (closed symbols) and weight loss (opened symbols) of matrix tablets during dissolution pH 6.8 at different agitation speed: (A) Alfuzosin®, (B) Preductal®, (C) Quetiapin®. Commercial product Tromphyllin® and Glucophage® were not available for this experiment.
See this image and copyright information in PMC

References

    1. Colombo P, Bettini R, Peppas NA. Observation of swelling process and diffusion front position during swelling in hydroxypropyl methyl cellulose (HPMC) matrices containing a soluble drug. J Control Release. 1999;61(1–2):83–91. doi: 10.1016/s0168-3659(99)00104-2. - DOI - PubMed
    1. Kavanagh N, Corrigan OI. Swelling and erosion properties of hydroxypropylmethylcellulose (Hypromellose) matrices--influence of agitation rate and dissolution medium composition. Int J Pharm. 2004;279(1–2):141–152. doi: 10.1016/j.ijpharm.2004.04.016. - DOI - PubMed
    1. Rajabi-Siahboomi AR, Bowtell RW, Mansfield P, Henderson A, Davies MC, Melia CD. Structure and behaviour in hydrophilic matrix sustained release dosage forms: 2. NMR-imaging studies of dimensional changes in the gel layer and core of HPMC tablets undergoing hydration. J Control Release. 1994;31(2):121–128. doi: 10.1016/0168-3659(94)00016-6. - DOI
    1. Colombo P, Bettini R, Santi P, de Ascentiis A, Peppas NA. Analysis of the swelling and release mechanisms from drug delivery systems with emphasis on drug solubility and water transport. J Control Release. 1996;39(2–3):231–237. doi: 10.1016/0168-3659(95)00158-1. - DOI
    1. Colombo P, Bettini R, Catellani PL, Santi P, Peppas NA. Drug volume fraction profile in the gel phase and drug release kinetics in hydroxypropylmethyl cellulose matrices containing a soluble drug. Eur J Pharm Sci. 1999;9(1):33–40. doi: 10.1016/s0928-0987(99)00039-1. - DOI - PubMed