Probing the Mechanisms of Drug Release from Hydroxypropylmethyl Cellulose Matrices |
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Authors: | Pham Anh Thu Lee Ping I |
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Institution: | (1) Faculty of Pharmacy, University of Toronto, Toronto, Ontario, M5S 2S2, Canada;(2) Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 1A4, Canada;(3) Present address: Schering-Plough Research Institute, Kenilworth, New Jersey, 07033;(4) Present address: Glaxo Canada Inc., Mississauga, Ontario, L5N 6L4, Canada;(5) Schering-Plough Research Institute, 2000 Galloping Hill Road, Kenilworth, New Jersey, 07033 |
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Abstract: | The transient dynamic swelling and dissolution behavior during drug release from hydroxypropylmethyl cellulose (HPMC) matrices was investigated using fluorescein as a model drug. A new flow-through cell capable of providing a well-defined hydrodynamic condition and a non-destructive mode of operation was designed for this purpose to assess the associated moving front kinetics. The results obtained show a continuous increase in transient gel layer thickness irrespective of the polymer viscosity grade or drug loading. This is attributed to the faster rate of swelling solvent penetration than that of polymer dissolution under the present experimental condition. On the other hand, the observed shrinkage of sample diameter over a longer time period demonstrates that polymer dissolution does indeed occur in HPMC matrices. Further, both the rates of polymer swelling and dissolution as well as the corresponding rate of drug release increase with either higher levels of drug loading or lower viscosity grades of HPMC. For water-soluble drugs, the present results suggest that the effect of HPMC dissolution on drug release is insignificant and the release kinetics are mostly regulated by a swelling-controlled diffusional process, particularly for higher viscosity grades of HPMC. |
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Keywords: | hydroxypropylmethyl cellulose (HPMC) swelling dissolution moving front kinetics release mechanism fluorescein flow-through cell |
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