الفهرس 
Physicochemical characters
Zaleplon loaded self-nanoemulsifying powders (SNEPs)Only 14 pages are availabe for public view
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Abstract
Zaleplon is classified chemically as a non-benzodiazepine drug which used as sedative and hypnotic for management of insomnia. It shows pharmacological properties due to its interaction with GABA (A) receptor in the brain. Zaleplon exhibited an anticonvulsant effect against electroshock and pentylenetetrazole-induced seizures. According to the biopharmaceutical classification system (BCS), Zaleplon is categorized as a class II drug with high permeability and poor aqueous solubility. Drug bioavailability after oral administration is approximately 30% due to extensive first-pass metabolism. Rapid absorption of Zaleplon following oral intake was reported; however limited aqueous solubility hurdled its oral absorption due to poor dissolution which represented the ratelimiting step. The oral delivery of Zaleplon has some disadvantages which restricted its therapeutic application. The most common disadvantages are low oral bioavailability, short elimination half-life (1hr), delayed onset of action and early morning awakening which requires frequent treatment with high doses to keep its concentration within the therapeutic range. The required high dose is mainly responsible for the occurrence of typically short-lived hallucinations. The marketed immediate-release tablets or capsules of Zaleplon failed to eradicate previously mentioned disadvantages therefore, different formulation approaches such as micronization, solid dispersions, semisolid dispersions with lipid surfactants and complexation with cyclodextrins were adopted to overcome the aforementioned limitations of Zaleplon. Carrier-mediated drug delivery systems such as proliposomes, nanoemulsifying powders, solid lipid nanoparticles and nanoemulsions have been reported to achieve the above objectives. The ultimate goal of these Development and characterization of Polymeric Nanoparticles for a Model Class II Drug 2 strategies was to improve the low oral bioavailability of Zaleplon by improving the dissolution behaviour. Polymeric nanoparticles (PNPs) may have superiority over previously discussed strategies due to its high chemical and physical stability for longterm storage after freeze-drying. Polymeric nanoparticles are suitable carriers for small molecules, peptides, proteins or oligonucleotides with different fabrication methods. Polymeric nanoparticles can sustain drug release for long duration and offer the opportunity for passive and active drug targeting. In addition, encapsulation of lipophilic drug into nanoparticles may contribute to avoid its first pass metabolism by protecting it from being metabolized by the liver before renal excretion. This was proved by enhancement of serum concentrations of drug loaded into nanoparticles with respect to the administrated free drug solution or suspension. Eudragit® RS100 is a positively charged poly (ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) copolymer. Eudragit® RS100 is a swellable insoluble polymer at physiological pH which represents a good carrier for drug dispersion. It possesses positively charged quaternary ammonium groups, which are responsible for bioadhesive properties of the polymer. The aim of this study was to formulate, optimize, and characterize Zaleplon loaded Eudragit RS 100 polymeric nanoparticles in-vitro and investigates its pharmacological activity in-vivo using experimental rats. On the sidelines of this study, a validated HPLC analytical method for determination of Zaleplon in aqueous solutions will be established and used in all analytical procedures in this study.