Micron‐Size Drug Particles: Common and Novel Micronization Techniques

Abstract

Drug powders containing micron-size drug particles are used in several pharmaceutical dosage forms. Many drugs, especially newly developed substances, are poorly water soluble, which limits their oral bioavailability. The dissolution rate can be enhanced by using micronized drugs. Small drug particles are also required in administration forms, which require the drug in micron-size size due to geometric reasons in the organ to be targeted (e.g., drugs for pulmonary use). The common technique for the preparation of micron-size drugs is the mechanical comminution (e.g., by crushing, grinding, and milling) of previously formed larger particles. In spite of the widespread use of this technique, the milling process does not represent the ideal way for the production of small particles because drug substance properties and surface properties are altered in a mainly uncontrolled manner. Thus, techniques that prepare the drug directly in the required particle size are of interest. Because physicochemical drug powder properties are decisive for the manufacturing of a dosage form and for therapeutic success, the characterization of the particle surface and powder properties plays an important role. This article summarizes common and novel techniques for the production of a drug in small particle size. The properties of the resulting products that are obtained by different techniques are characterized and compared.

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism

“…Therefore, CLZ has been used as a therapeutic agent for the improvement of symptoms in conditions such as cancer (2), pain accompanying chronic arterial obstruction (3), and for the amelioration (4) and, prevention of cerebral infarction (5). The agent is only administered orally because of its low water-solubility (6). However, most patients with cerebral infarction have serious secondary conditions, such as impaired consciousness or aphagia (7).…”

Hybrid aerogel preparations as drug delivery matrices for low water-solubility drugs

“…Physical modifications, such as particle size reduction of amorphous 60 synthesis, often aim to increase the surface area, solubility and wettability of the drug particles. Different proposed strategies are those based on the 61 formulation of solid mixtures or matrix dispersions (Rasenack and Müller, 2004;Kerc et al, 1999;Elvira et al, 2004). Poorly water soluble crystalline drugs 62 are preferentially formulated as molecular dispersions in porous matrices.…”

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

“…For example, milling offers low opportunity to produce particles with controlled characteristics such as size, shape and surface properties (Snow et al, 1984). Jet-milled particles usually exhibit broad size distributions, irregular shapes (Rasenack and Müller, 2004), and high levels of electrostatic charges, resulting in increased interparticle cohesive forces and potentially leading to poor product performance (Brodka-Pfeiffer et al, 2003;Kaialy, 2016). Moreover, jet-milling is incompatible with thermally sensitive materials and may raise safety worries due to dust exposure during processing (Tong and Chow, 2006).…”