## 1 Introduction  
Spiramycin, a mixture of three 16-membered macrolide antiparasitics and antibiotics [1; 2; 3], is produced by _Streptomyces ambofaciens_. Spiramycin I (over 85%) is the main derivative of spiramycin, while spiramycin II and III, with percentages respectively lower than 5% and 10%, are minor derivatives. The chemical structures are presented in Figure 1. The quantity of each component varies according to the manufacturer. It has been widely used in the treatment of various infections of soft tissues, such as digestive [4], respiratory [4], urinary, and reproductive systems [5], as well as toxoplasmosis [6] and cryptosporidiosis [7]. Spiramycin also shows antimicrobial activities toward Gram-positive cocci and rods, Gram-negative cocci, and also mycoplasmas, chlamariae, and spirochetes. In addition, the antibiotic activity of spiramycin has been found to inhibit the protein synthesis in the bacterial cell during translocation [8; 9]. Spiramycin is also an important veterinary drug in China, Europe, and some other countries. Several factors potentially influencing the bioavailability of the drug include membrane permeability, solubility, and the dissolution rate of the drug; among these factors the solubility and dissolution rate of the poorly water-soluble drug are two key factors for its bioavailability. Spiramycin (BCS-class III) with low solubility and slow dissolution rate in water, results in its variable and incomplete oral bioavailability [5]. In recent years, many studies have committed to improving the solubility and dissolution rate of poorly water-soluble drugs through solid dispersion [10; 11; 12] and micronization [13]. The reduction of the drug particle size to submicron range will lead to a higher oral bioavailability, which has gained much attention. According to Noyes-Whitney equation [14], the dissolution rate of drug is proportional to the surface area of drug particles exposed to the dissolution medium. Therefore, application of some techniques for reducing the particles size of spiramycin is conducive to facilitating the dissolution through enlarging the effective surface area of spiramycin. For the preparation of microparticles, many traditional approaches have been applied, including ball milling [15], mechanical communication [16], air jet pulverization [17; 18], supercritical fluid technology [19; 20; 21; 22; 23], high pressure homogenization [24; 25], reactive crystallization [26], spray drying [27; 28], and the antisolvent precipitation process [29]. The mechanical commitment process is a widely used method for micronizing drugs in pharmaceutical manufacturing. However, some disadvantages exist in these techniques, such as the large capital equipment investment for the application of supercritical fluid technology, expensive equipment, and solvent requirements for the technique of high pressure homogenization. By contrast, the antisolvent precipitation technique has some advantages, such as lower reagent consumption, higher process efficiency, and easy operation [30; 31], and has been widely applied. Particle size is an important factor influencing the dissolution rate, the reduction of which can essentially shorten the dissolution time and improve the overall dissolution rate. Homogenization, an effective pulverization technique, has been widely applied in the pretreatment of animal and plant tissues, and the extraction of plant ingredients. The homogenate process has good pulverization efficiency because of stronger mechanical shearing forces and fluid cutting action, and smashing without heating and pressure. In the antisolvent precipitation process, simultaneous use of the homogenate technique for treatment will further prevent the formation and growth of crystal particles. However, the homogenate technique, in combination with antisolvent precipitation, has not been reported in the literature. Here, we prepare spiramycin microparticles using a homogenate-antisolvent precipitation (HAP) process, and evaluate its physicochemical properties and dissolution in vitro.