Comparison between aqueous and non-aqueous solvent evaporation methods for microencapsulation of drug–resin complexes

Abstract

Terbutaline-loaded ion-exchange resins were entrapped within cellulose acetate butyrate (CAB) microcapsules using either an aqueous (O/W) or a non-aqueous (O/O) solvent evaporation method. Scanning electron micrographs of the cross-sections of microcapsules prepared by both techniques revealed that the degree of multinucleation was dependent on the polymer concentration. A low polymer concentration led to a typical mononucleated reservoir structure whereas more multicore microcapsules were formed at high polymer concentrations. These differences on the inner structure affected the in vitro terbutaline release profiles. Terbutaline released very rapidly from the mononucleated microcapsules, however its release was controlled from the multinucleated systems. In addition, terbutaline release was influenced by the microencapsulation method. Using the higher CAB concentrations, the O/O technique produced microcapsules which adequately controlled the release of terbutaline; in contrast, microcapsules obtained by the O/W method showed a biphasic behaviour, with an initial burst effect followed by stabilization of the drug release, which became finally incomplete. With the aim of elucidating the main causes which were responsible for the differences in drug release, CAB films were obtained by casting the polymeric solutions prepared with the solvents used in each encapsulation procedure, acetone and methylene chloride for O/O and O/W methods, respectively. Thermal properties of the polymer in films and microcapsules were compared, and terbutaline diffusion studies through the films were performed. Results revealed that the polymer solvent was a key factor that determined the structure of the polymer wall formed, and thereby the in vitro release properties of the polymer films. After an initial rapid permeation step in both films, the CAB film cast from acetone allowed a faster permeation of terbutaline by diffusion through the pores, whereas the diffusion through the polymer chains was probably the only possible mechanism of drug release in the dense film formed from methylene chloride polymer solutions, this process being extremely slow for terbutaline.