T he objective of this study was to prepare a nanoparticulate formulation of simvastatin (SV) for improving oral bioavailability and sustaining the drug release while investigating the effect of various formulation parameters on characteristics of nanoparticles. Nanoparticles containing SV were prepared by a modified emulsification solvent evaporation technique using a biodegradable polymer, poly(d,l-lactide-coglycolide) (PLGA) as a sustained release carrier. The effect of various formulation parameters such as drug polymer ratios (SV:PLGA, 1:4 to 1:1), organic solvents (methanol/dichloromethane), and surfactants (PVA/polysorbate-80) in a fixed concentration (0.5%, w/v) were studied for particle size, drug loading, and entrapment efficiency. Nanoparticles were characterized by differential scanning calorimetry (DSC) and their shapes were observed by scanning electron microscopy (SEM). An aqueous solubility study indicated that the dissolution rates were remarkably increased for nanoparticles compared with the drug alone. The in vitro drug release study of the nanoparticles showed a biphasic release pattern: one initial burst release of 40.56% in the first 4 h which can be helpful to improve the penetration of drug followed by a second slow-release phase (extended release) consistent with a Higuchi diffusion mechanism. The hypolipidemic activity of nanoparticles was determined in comparison with SV in male Wistar rats for changes in total cholesterol (CH) and triglyceride (TG) levels in blood. Nanoparticles showed a significantly better in vivo performance than SV in reducing total CH and TG levels which is primarily attributed to the improved solubility and dissolution of nanoparticles. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of SV having great potential to improve the oral bioavailability and sustain the drug release, thereby minimizing the dose-dependent adverse effects and maximizing the patient's compliance.

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To understand the formation of direct chill (DC)-casting defects, e.g., butt curl and crack formation, it is essential to take into account the effect of temperature variation, strain rate, and their role in the constitutive behavior of the DC-cast alloys. For the correct prediction of defects due to thermal stresses during DC casting, one needs to rely on the fundamentals of mechanisms that may be relevant to the temperatures at below solidus temperatures. This research work aims to find a suitable physically based model for the as-cast aluminum alloys, namely AA3104, AA5182, and AA6111, which can describe the constitutive behavior at below solidus temperatures during complex loading conditions of temperatures and strain rates. In the present work, an earlier measured and modeled (Alankar and Wells, 2010, “Constitutive Behavior of As-Cast Aluminum Alloys AA3104, AA5182 and AA6111 at Below Solidus Temperatures,” Mater. Sci. Eng. A, 527, pp. 7812–7820) stress–strain data are analyzed using the Voce equation and Kocks–Mecking (KM) model. KM model is capable of predicting the hardening and recovery behavior during complex conditions of strain, strain rate, and temperatures during DC casting. Recovery is dependent on temperature and strain rate, and thus, relevant parameters are determined based on the temperature-sensitive annihilation rate of dislocations. For the KM model, we have estimated k1 parameter as a function of temperature, and k2 has been further modeled based on the temperature and strain rate. KM model is able to fit the constant temperature uniaxial tests within 1.5% of the regenerated data.

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