title: Formulation and evaluation of a salted-out isoniazid-loaded nanosystem.
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.
authors.affiliation: Division of Pharmaceutics, Department of Pharmacy and Pharmacology, University of Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Iyuke
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D007538:Isoniazid / Q000008:administration & dosage / Q000737:chemistry*; D008422:Materials Testing; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012492:Salts / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D012492:Salts; D007538:Isoniazid