Manufacturing monodisperse chitosan microparticles containing ampicillin using a microchannel chip Chih-Hui Yang · Keng-Shiang Huang · Jia-Yaw Chang Published online: 19 December 2006 Abstract The purpose of this study was using a developed microfluidic chip to prepare size-controlled monodisperse chitosan microparticles encapsulating ampicillin. Our strat- egy is that a chitosan aqueous solution (the disperse phase) is fed into the microfluidic chip equipped with a cross-junction microchannel, and is sheared by the viscous oil flows (the continuous phase) to form monodisperse semi-product, chi- tosan emulsions. These fine emulsions are then gelled into stability upon gelation by injection of copper sulfate solu- tion at the terminal microchannel of the microfluidic chip, and finally the uniform chitosan microparticles are formed in an efficient manner. The proposed chip is fabricated by a CO 2 laser machine on a conventional poly methyl methacry- late (PMMA) substrate. This microfluidic chip has four in- let ports, one cross-channel and one outlet port. We have demonstrated that one can control the size of chitosan mi- croparticles from 100 to 800 μm in diameter (with a variation less than 5%) by altering the relative sheath/sample flow rate ratio. Experimental data showed that when given a steady continuous phase (oil flow), the emulsion size increases with the increase in average velocity of the dispersed phase flow (sample flow). In addition, the release of the model drug (ampicillin) from these microspheres is proved to be once- daily for clinical application. We also revealed that appro- priate particle sizes for different release patterns are pre- dictable, enabling better applications of chitosan as a drug carrier. C.-H. Yang () · K.-S. Huang · J.-Y. Chang Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan, R.O.C. e-mail: chyang@isu.edu.tw Keywords Chitosan . Microfluidic . Monodisperse . Emulsions . Ampecillin 1 Introduction Chitosan is currently gaining a great deal of attention for medical and pharmaceutical applications (Sinha et al., 2004; Dodane and Vilivalam, 1998; Paul and Sharma, 2000). Chitosan is a linear polysaccharide obtained by chemical deacetylation of chitin which is the structural component in the exoskeleton of crustaceans (shrimp, crabs, etc.) and the cell wall of fungi (Aiba, 1992). Due to its biocompatibility and biodegradability, and it can improve efficacy of wound healing, reduce toxicity, and improve uptake, the chitosan particles have been used in the development of drug deliv- ery systems in recent years (Guliyeva et al., 2006; Ko et al., 2002; Agnihotri et al., 2004). Several methodologies for the production of chitosan par- ticles have been described in the literature, including coacer- vation (precipitation), spray-drying (atomization), emulsion techniques, and others (He et al., 1999; van der Lubben et al., 2001; Kawashima et al., 1998; Young et al., 1999; Mironov et al., 2005; Lee et al., 2006). However, the resulting size and size distribution of the microparticles cannot be easily controlled by these methods. Control of the particle size and the size distribution is important for controlled-release drug delivery, because they influence the clearance rate from the body and ultimately determines the drug dosage (Berklan et al., 2001). Basically, an ideal particle size could provide the optimal release rate and route of administration. Many researchers have attempted to make smaller parti- cles, but less attention has been paid to make monodisperse particles (Lee et al., 2006; Berklan et al., 2001; You et al., 2001; Sugiura et al., 2005; Iwamoto et al., 2002). Recently,