Formulation and evaluation of a salted-out isoniazid-loaded nanosystem
Division of Pharmaceutics, Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa; School of Chemical and Metallurgical Engineering, University of the Witwatersrand, P/Bag 3, Wits, Johannesburg 2050, South Africa
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. © American Association of Pharmaceutical Scientists 2007.
acrylic acid ethyl ester; dispersant; isoniazid; methacrylic acid; nanomaterial; nanoparticle; polymer; zinc sulfate; inorganic salt; isoniazid; nanomaterial; polymethacrylic acid derivative; tuberculostatic agent; article; conductance; controlled drug release; cross linking; dielectric constant; drug delivery system; drug formulation; emulsion; intermethod comparison; nanotechnology; particle size; perceptron; zeta potential; chemistry; delayed release formulation; diffusion; drug formulation; drug screening; materials testing; methodology; ultrastructure; Antitubercular Agents; Delayed-Action Preparations; Diffusion; Drug Compounding; Drug Evaluation, Preclinical; Isoniazid; Materials Testing; Nanostructures; Particle Size; Polymethacrylic Acids; Salts