Preparation of stable colloidal suspensions of superdisintegrants via wet stirred media milling

Superdisintegrants are cross-linked polymers that can be used as dispersants for fast release of drug nanoparticles from nanocomposite microparticles during in vitro and in vivo dissolution. Currently avail- able superdisintegrant particles have average sizes of approximately 5-130 μm, which are too big for drug nanocomposite applications. Hence, production of stable superdisintegrant suspensions with less than 5 μm particles is desirable. Here, we explore the preparation of colloidal suspensions of anionic and nonionic superdisintegrants using a wet stirred media mill and assess their physical stability. Sodium starch glycolate （SSG） and crospovidone （CP） were selected as representative anionic and nonionic superdisintegrants, and hydroxypropyl cellulose （HPC） and sodium dodecyl sulfate （SDS） were used as a steric stabilizer and a wetting agent/stabilizer, respectively. Particle sizing, scanning electron microscopy, and zeta potential measurements were used to characterize the suspensions. Colloidal superdisintegrant suspensions were prepared reproducibly. The extensive particle breakage was attributed to the swelling-induced softening in water. SSG suspensions were stable even in the absence of stabilizers, whereas CP suspensions required HPC-SDS for minimizing particle aggregation. These findings were explained by the higher absolute （negative） zeta potential of the suspensions of the anionic superdisintegrant （SSG） as compared with those of the nonionic superdisintegrant （CP）.

Overview of milling techniques for improving the solubility of poorly water-soluble drugs

Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a“topedown”approach in the production of fine particles.Fine drug particulates are especially desired in formulations designed for parenteral,respiratory and transdermal use.Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents,often to enhance processability or solubility especially for drugs with limited aqueous solubility.The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size,specific surface area and shape of the drug particles as well as millinginduced amorphization and/or structural disordering of the drug crystal(mechanochemical activation).Technology advancements in milling now enable the production of drug micro-and nano-particles on a commercial scale with relative ease.This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs.Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.

Simulation of a Laboratory Scale Ball Mill via Discrete Element Method Modelling

Discrete Element Method (DEM) is a powerful tool for simulating different types of mills. It also used for computing different types of particles such as rocks, grains, and molecules. DEM has been widely used in the field of rock mechanics. In the present work, DEM approach is applied to model the milling media (powder particles and balls) inside a planetary ball mill and to estimate the distribution of particles of a dry powder during milling. In fact, the efficiency of the DEM strongly depends on the input parameters. The DEM simulation results indicated that DEM is a promising tool for the simulation of the dynamic particles motion and interactions within planetary ball mill. These results could be utilized to further develop the synthesis performance, anticipate the reaction, and reduce the wear in the dry milling reactions.