Role of the solvent-diffusion-rate modifier in a new emulsion solvent diffusion method for preparation of ketoprofen microspheres

Abstract

A new emulsion solvent diffusion method to prepare the microspheres of ketoprofen with an acrylic polymer was developed by utilizing sugar esters as solvent diffusion modifiers. The microspheres were produced via transient o/w emulsion droplets of the polymer, which was formed by the interaction of drug and water-miscible organic solvent, e.g. ethanol. The solvent consisting in oil droplets diffused into the outer aqueous medium. In the droplets, ethanol interacted with ketoprofen via hydrogen bonding between -OH group of ethanol and both -COOH and = CO groups of ketoprofen. These hydrogen bonds made ethanol solution strongly hydrophobic. The sugar ester added in the ethanol could inhibit such intermolecular interaction between ethanol and the = CO group of ketoprofen. Modulation in the binding force of ketoprofen-ethanol by the sugar ester contributed to achieving a desirable initial ethanol diffusion rate from the oil droplets for the formation of ketoprofen microspheres with high yield (> 85 per cent) and drug entrapment ratio (> 90 per cent).

Floating Properties and Release Characteristics of Hollow Microspheres of Acyclovir

“…The hollow microspheres without drug were prepared by o/w emulsion solvent evaporation diffusion method modified from the methods previously reported (Kawashima et al 1992(Kawashima et al , 1993Crotts and Park 1995;Lee et al 1999Lee et al , 2000El-Kamel et al 2001;Soppimath et al, 2001). Eudragit S 100 was used as a controlled release polymer.…”

“…The polymer microspheres are multiple-unit systems, which can be prepared by emulsion solvent diffusion method 332 V. B. JUNYAPRASERT AND S. PORNSUWANNAPHA (Malamataris and Avgerinos 1990;Kawashima et al 1991Kawashima et al , 1992Kawashima et al , 1993Thanoo et al 1993;Crotts and Park 1995;Jayanthi et al 1995;Scholes 1998;Lee et al 1999Lee et al , 2000El-Kamel et al 2001;Soppimath et al 2001). This method has been the most widely used since it is known to be simple and able to be produced in a small batch size (Swarbrick and Baylan 1994;Quintanar-Guerrero et al 1998a, 1998bScholes 1998;Mathiowitz 1999).…”

Formulation and Characterization of Sustained Release Floating Microballoons of Metformin Hydrochloride

“…It has been reported that when the diffusion rate of solvent out of emulsion droplet is too slow, microspheres coalesce together. Conversely, when the diffusion of solvent is too fast, the solvent may diffuse into the aqueous phase before stable emulsion droplets are developed, causing aggregation of embryonic microsphere droplets [20]. The results of this study indicate that the formation of microballoons is a function of process variables such as polymer concentration, solvent composition, rate of agitation and temperature.…”

In vitro Evaluation of Novel Sustained Release Microspheres of Glipizide Prepared by the Emulsion Solvent Diffusion-Evaporation Method

“…Kawashima et al .,[12] reported that when the diffusion rate of solvent from the organic phase emulsion droplet was too slow, microspheres coalesced together. In another study,[13] he reported that when it was too fast; the solvent may diffuse into the aqueous phase before stable emulsion droplets were formed, causing the aggregation of embryonic microspheres droplets.…”