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Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion
Malode, V.N. Devarajan, P.V.
Malode, V.N.
Devarajan, P.V.
Publication Date
2015-06-30
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© 2015 Elsevier. This is the accepted version of the article above, which has been published in final form at the link above. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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2015-06-24
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Abstract
We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit® RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit® RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 minutes but inadequate total floating time (TFT) of 3 hours. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12 hours with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24 hours and t90% of 10.12 hours. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40 °C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates.
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Accepted manuscript
Citation
Malode VN, Paradkar AR and Devarajan PV (2015) Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion. International Journal of Pharmaceutics. 491(1-2): 345-351.
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Article