Ammonolysis-based microencapsulation technique using isopropyl formate as dispersed solvent

Abstract

The objectives of this study were to develop an ammonolysis-based microencapsulation technique using a nonhalogenated isopropyl formate and to evaluate its feasibility in preparing poly-d,l-lactide-co-glycolide microspheres. The choice of isopropyl formate was based on its great reactivity toward ammonolysis and acceptance as a flavoring agent for human food by regulatory agencies. Progesterone was used as a model drug for microencapsulation. In the practice of this microencapsulation process, a dispersed phase consisting of isopropyl formate, the polymer and progesterone was emulsified in an aqueous phase. Solvent removal from emulsion droplets was rapidly achieved by ammonolysis at ambient conditions, not by typical solvent evaporation and/or extraction. Depending upon microsphere formulations, its encapsulation efficiency ranged from 88.0 ± 3.6 to 97.0 ± 3.6%. Analysis of FTIR spectra suggested that there were no significant chemical interactions between prednisolone and the polymer. Both DSC and XRD data substantiated that the magnitude of an actual progesterone loading influenced its physical status in the microspheres. Interestingly, the microspheres prepared in this study contained noticeably lower levels of solvent residues: a gas chromatographic analysis demonstrated that the levels of residual isopropyl formate found in different microspheres were not more than 0.34 ± 0.07%. It was seen to be feasible from these results that the ammonolysis-based approach using isopropyl formate might have a potential as an alternative microencapsulation technique. © 2009 Elsevier B.V. All rights reserved.