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Formulation and Evaluation of a Salted-out Isoniazid-loaded Nanosystem
Authors:Lisa C. du Toit  Viness Pillay  Yahya E. Choonara  Sunny E. Iyuke
Affiliation:(1) Division of Pharmaceutics, Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa;(2) School of Chemical and Metallurgical Engineering, University of the Witwatersrand, P/Bag 3, Wits, 2050, Johannesburg, South Africa
Abstract:The purpose of this study was to develop a drug-loaded nanosystem that has the ability to achieve flexible yet rate-controlled release of model drug isoniazid (INH) employing either an aqueous or emulsion-based salting-out approach. Formulation conditions were aimed at reducing the polymeric size with subsequent rate-modulated INH release patterns from the polymeric nanosystem. The emulsion-based salted-out nanosystems had particle sizes ranging from 77–414 nm and a zeta potential of −24 mV. The dispersant dielectric constant was set at 78.5 and a conductivity of 3.99 mS/cm achieved. The reduced nanosystem size of the aqueous-based approach has demonstrated an intrinsically enhanced exposure of methacrylic acid-ethyl acrylate to zinc sulphate which was employed as a crosslinking reagent. This resulted in robustly interconnected polymeric supports in which INH was efficiently embedded and subsequently released. The multi-layer perceptron data obtained showed that the aqueous and emulsion-based salting out approaches had Power (law) (MSE = 0.020) and Linear (MSE = 0.038) relationships, respectively. Drug release from the nanosystems occurred in two phases with an initial burst-release in aqueous-based nanosystems (30–100%) and significantly lower bursts observed in emulsion-based nanosystems (20–65%) within the first 2 h. This was followed by a gradual exponential release phase over the remaining 12 h. The nanosystems developed demonstrated the ability to control the release of INH depending on the formulation approach adopted.
Keywords:crosslinking  drug release  methacrylic acid-ethyl acrylate  nanoparticles  tuberculosis
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