Chronotherapeutic Drug Delivery from Indomethacin Compression Coated Tablets for Early Morning Pain Associated Rheumatoid Arthritis

Author(s): Songa Ambedkar Sunil, Meka Venkata Srikanth, Nali Sreenivasa Rao, Kolapalli Venkata Ramana Murthy

Journal Name: Current Drug Delivery

Volume 10 , Issue 1 , 2013

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As the main intent of delivering maximum concentration of drug available from the dosage form, an oral compression coated tablet (CCT) was intended to develop with a predetermined lag time of 6 hrs before immediate release of drug to target circadian rhythms of rheumatoid arthritis. Solid dispersions are promising approach to enhance drug release, which later will be developed as core tablet formulation and compression coated with polyethylene oxide (PEO WSR 303). Solid dispersions were formulated with different ratio of drug and carrier (sucrose fatty acid esters 1811) using solvent evaporation and melt granulation technique, optimized solid dispersion was formulated as core tablet with different diluents. Optimized core tablet was compression coated with PEO WSR 303 along with a channeling agent (DCL 21, mannitol, HPMC 5 cps and starch 1500). Lag time before immediate release of drug was markedly dependent on weight ratios of polymer and channeling agent used, which ranged from 4 to 12 hrs. Optimized solid dispersion (S9) was used for formulating optimized core tablet formulation (C8). CCT (T8) prepared with core tablet (C8) along with mannitol provided a lag time of 6 hrs with minimum concentration of channeling agent used, which was also supported from the permeability study results. Incompatibility and characterization was confirmed from DSC, XRD, FTIR and SEM studies. Unaltered Cmax and AUC0-t but delayed Tmax following oral ingestion of optimized formulation (T8) to human volunteers indicated clear lag time before immediate release of drug, which is suitable for treating rheumatoid arthritis following circadian rhythm.

Keywords: Compression coated tablet, lag time, in vivo study, Polyethylene oxide, Solid dispersions, Sucrose fatty acid ester

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Article Details

Year: 2013
Published on: 25 February, 2013
Page: [109 - 121]
Pages: 13
DOI: 10.2174/1567201811310010017

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