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Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

Authors

  • David S. Jones,

    Corresponding author
    1. Medical Polymers Research Institute, School of Pharmacy, Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom
    • Medical Polymers Research Institute, School of Pharmacy, Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom
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  • Brendan C. O. Muldoon,

    1. Medical Polymers Research Institute, School of Pharmacy, Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom
    Current affiliation:
    1. Warner Chilcott (UK) Ltd, Old Belfast Road, Larne BT40 2SH, Northern Ireland, United Kingdom.
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  • A. David Woolfson,

    1. Medical Polymers Research Institute, School of Pharmacy, Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom
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  • F. Dominic Sanderson

    1. GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
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Abstract

Despite their widespread use, there is a paucity of information concerning the effect of storage on the rheological properties of pharmaceutical gels that contain organic and inorganic additives. Therefore, this study examined the effect of storage (1 month at either 4 or 37°C) on the rheological and mechanical properties of gels composed of either hydroxypropylmethylcellulose (3–5% w/w, HPMC) or hydroxyethylcellulose (3–5% w/w, HEC) and containing or devoid of dispersed organic (tetracycline hydrochloride 2% w/w) or inorganic (iron oxide 0.1% w/w) agents. The mechanical properties were measured using texture profile analysis whereas the rheological properties were analyzed using continuous shear rheometry and modeled using the Power Law model. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing polymer concentration (3–5% w/w) significantly increased the consistency, hardness, compressibility, and adhesiveness of the formulations due to increased polymer chain entanglement. Following storage (1 month at 4 and 37°C) the consistency and mechanical properties of additive free HPMC gels (but not HEC gels) increased, due to the time-dependent development of polymer chain entanglements. Incorporation of tetracycline hydrochloride significantly decreased and increased the rheological and mechanical properties of HPMC and HEC gels, respectively. Conversely, the incorporation of iron oxide did not affect these properties. Following storage, the rheological and mechanical properties of HPMC and HEC formulations were markedly compromised. This effect was greater following storage at 37 than at 4°C and, additionally, greater in the presence of tetracycline hydrochloride than iron oxide. It is suggested that the loss of rheological/mechanical structure was due to chain depolymerization, facilitated by the redox properties of tetracycline hydrochloride and iron oxide. These observations have direct implications for the design and formulation of gels containing an active pharmaceutical ingredient. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 852–859, 2005

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