Nanoparticles could be prepared by two different techniques, depending on the technology used to
achieve the nanosization. They are prepared either
by particle size reduction of large crystal
“top-down techniques” or by increasing the particle size from small to large size by precipitation of
dissolved 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/or
high-pressure homogenization. Ball
milling is one of the top-down nanonization techniques, that based on mixing
the drug powder with dispersion media (mostly water) and suitable stabilizer
that helps to avoid or minimize the particle aggregation after the preparation
of nanoparticles (Chen et al., 2011; Loh et al., 2015; Salazar et al., 2014).
The milling media
(balls) are available in many types like zirconium dioxide beads, silicium nitride beads and polysterene beads. High shear forces resulting
in nanonizing will be obtained when vessel jackets rotate at a very high speed (Chen et al., 2011; Loh et al., 2015). Several parameters
can affect the resulting particle size of ball milling
nanonization methods such as the amount of drug, type
, concentration of stabilizers, the amount and size of the ball, speed, time,
and temperature. Many drugs
have been nanonized using this method for the production of drug
nanoparticles like fenofibrate, naproxen and
ibuprofen. Some of these drugs are available in the pharmaceutical markets as
tablet forms, such as fenofibrate, ibuprofen, and paliperidone palmitate (Chen
et al., 2011; Loh et al., 2015; Salazar et al., 2014).
Preparation of the
drug in nanoparticles might be accompanied by physical instability, which leads to an increase
in the free energy of the system resulting in aggregation of the particles to
form a large particle. This phenomenon is
called Ostwald ripening, so it is important to be limited or avoided (Wang et al., 2013; Verma et al., 2011). An addition
of a stabilizer to the formulation can
play an important role in nanoparticle physical stability by reducing the free energy of the system during
nanosization process. The stabilizer may be used
either (i) surfactants such as sodium
lauryl 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 hydroxymethyl
glutaryl-coenzyme A reductase inhibitor (statin) used as a cholesterol-lowering
agent in human by inhibiting HMG-CoA reductase. Its bioavailability is very low
With this background, the purpose of the current
study was to formulate, characterize, and stabilize SIM nanoparticle produced
by planetary ball mill to enhance its dissolution rate.