Nanoparticles like fenofibrate, naproxen and ibuprofen. Some of these

Nanoparticles could be prepared by two different techniques, depending on the technology used toachieve the nanosization. They are prepared eitherby particle size reduction of large crystal “top-down techniques” or by increasing the particle size from small to large size by precipitation ofdissolved molecules “bottom-up techniques” (Van Eerdenbrugh et al., 2008). Top-down techniques are most commonly used for nanonization.

These techniques can be applied using either media milling and/orhigh-pressure homogenization.  Ballmilling is one of the top-down nanonization techniques, that based on mixingthe drug powder with dispersion media (mostly water) and suitable stabilizerthat helps to avoid or minimize the particle aggregation after the preparationof nanoparticles (Chen et al., 2011; Loh et al., 2015; Salazar et al.

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, 2014). The milling media(balls) are available in many types like zirconium dioxide beads, silicium nitride beads and polysterene beads. High shear forces resultingin nanonizing will be obtained when vessel jackets rotate at a very high speed (Chen et al., 2011; Loh et al., 2015). Several parameterscan affect the resulting particle size of ball millingnanonization methods such as the amount of drug, type, concentration of stabilizers, the amount and size of the ball, speed, time,and temperature. Many drugshave been nanonized using this method for the production of drugnanoparticles like fenofibrate, naproxen andibuprofen.

Some of these drugs are available in the pharmaceutical markets astablet forms, such as fenofibrate, ibuprofen, and paliperidone palmitate (Chenet al., 2011; Loh et al., 2015; Salazar et al., 2014).Preparation of thedrug in nanoparticles might be accompanied by physical instability, which leads to an increasein the free energy of the system resulting in aggregation of the particles toform a large particle.

This phenomenon iscalled Ostwald ripening, so it is important to be limited or avoided (Wang et al., 2013; Verma et al., 2011). An additionof a stabilizer to the formulation canplay an important role in nanoparticle physical stability by reducing the free energy of the system duringnanosization process. The stabilizer may be usedeither (i) surfactants such as sodiumlauryl sulfate and poloxamer 188, or (ii) polymers such as hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone(PVP) (Wang et al.

, 2013; Verma et al., 2011) .Simvastatin (SIM), is hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) used as a cholesterol-loweringagent in human by inhibiting HMG-CoA reductase. Its bioavailability is very low(about 5%).With this background, the purpose of the currentstudy was to formulate, characterize, and stabilize SIM nanoparticle producedby planetary ball mill to enhance its dissolution rate.