Moodley K., Choonara Y.E., Kumar P., Du Toit L.C., Pillay V.
Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, South Africa
Moodley, K., Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, South Africa; Choonara, Y.E., Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, South Africa; Kumar, P., Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, South Africa; Du Toit, L.C., Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, South Africa; Pillay, V., Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, South Africa
Objectives: The purpose of this study was to formulate novel triple-layered tablet (TLT) matrices employing modified polyamide 6,10 (mPA6,10) and salted-out poly(lactic-co-glycolic acid) (s-PLGA) in an attempt to achieve stratified zero-order drug release.Methods: mPA6,10 and s-PLGA were employed as the outer drug-carrier matrices, whereas poly(ethylene oxide) (PEO) was used as the middle-layer drug matrix. Diphenhydramine HCl, ranitidine HCl and promethazine were selected as model drugs to pre-optimize the TLT, whereas atenolol, acetylsalicylic acid and simvastatin were employed as a comparable fixed dose combination to test the TLT prototype in vitro and in vivo (Large White Pig model). A total of 17 formulations that varied in terms of polymer stoichiometry, salt addition and polymer-polymer ratios were generated using a Box-Behnken experimental design.Results: The in vitro drug release analysis revealed that release from the mPA6,10 layer was relatively linear with a burst release, which upon addition of sodium sulfate was reduced. Furthermore, formulations with higher quantities of mPA6,10 provided more controlled zero-order drug release and increased the matrix hardness. The addition of PEO to the s-PLGA layer significantly reduced the initial burst release that occurred when s-PLGA was used alone.Conclusions: The formulation with a lower s-PLGA:PEO ratio displayed superior zero-order release. Relatively, linear drug release was achieved from the middle-layer. The in vivo results proved the applicability of optimized TLT formulation in a therapeutic cardiovascular drug treatment regimen. © 2015 Informa UK, Ltd.
acetylsalicylic acid; atenolol; diphenhydramine; drug carrier; macrogol; polyamide; polyglactin; promethazine; ranitidine; simvastatin; sodium sulfate; delayed release formulation; lactic acid; macrogol derivative; nylon; nylon 6-10; polyglycolic acid; polylactic acid-polyglycolic acid copolymer; polymer; tablet; animal experiment; Article; chemical structure; computer model; controlled study; differential scanning calorimetry; drug blood level; drug disposition; drug release; drug solubility; drug stability; gastrointestinal transit; in vitro study; in vivo study; molecular mechanics; molecular model; nonhuman; nuclear magnetic resonance imaging; porcine model; tablet disintegration; tablet formulation; tablet hardness; tablet matrix; triple layered tablet matrix; chemistry; computer simulation; delayed release formulation; drug delivery system; drug release; medicinal chemistry; procedures; tablet; Chemistry, Pharmaceutical; Computer Simulation; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Liberation; Lactic Acid; Nylons; Polyethylene Glycols; Polyglycolic Acid; Polymers; Tablets