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  • The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies

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    Author(s)
    Gardyne, Stephen J.
    Mucalo, Michael R.
    Rathbone, Michael
    Griffith University Author(s)
    Rathbone, Michael
    Year published
    2011
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    Abstract
    Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17߬ and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has ...
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    Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17߬ and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(e-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122 姠h-1 with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 姠h-1. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0-556 姠cm-2 h-0.5 with dexamethasone, dexamethasone valerate, ketoprofen, melatonin, and progesterone giving values exceeding 100 姠cm-2 h-0.5. A number of drugs such as the dexamethasones probably performed better than they did in the permeability rate measurements because of the less polar aqueous alcoholic solvent used. In searching for useful correlations between the drug physicochemical properties and release rate, only a moderate correlation (R2=0.5675) between Hanson dissolution release rate and permeation rate was found. This suggests that the release rate and the permeation are both controlled by the rate of drug diffusion through the PCL with release rate involving an additional dissolution process (of the drug) before permeation occurs accounting for the moderate correlation. In general, of the eight drugs considered, it was clear that the oestradiol-based drugs, abamectin, and amoxicillin were generally not suited to drug delivery via PCL under the conditions used. However, ketoprofen was found to be very suitable as a drug candidate for melt extrusion with PCL with dexamethasone valerate, dexamethasone, and melatonin also showing potential as candidates though to a much lesser extent.
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    Journal Title
    Results in Pharma Sciences
    Volume
    1
    Issue
    1
    DOI
    https://doi.org/10.1016/j.rinphs.2011.11.002
    Copyright Statement
    © 2011 The Authors. Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution-NonCommercial--ShareAlike 3.0 Unported (CC BY-NC-SA 3.0) (http://creativecommons.org/licenses/by-nc-sa/3.0/) which permits unrestricted, non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
    Subject
    Pharmacology and Pharmaceutical Sciences not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/45497
    Collection
    • Journal articles

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