Controlled-release liquid suspensions based on ion-exchange particles entrapped within acrylic microcapsules

Abstract

Eudragit® RS/RL polymers were used to prepare microcapsules containing terbutaline-loaded ion-exchange resins, with the final aim of formulating this anti-asthmatic drug in a controlled-release liquid form. Oil-in-oil (o/o) and oil-in-water (o/w) solvent evaporation procedures were conveniently modified in order to encapsulate the resin cores. The microcapsules were then suspended in a hydroxypropylmethylcellulose solution of adequate viscosity and palatability, and stored at 20°C and ambient humidity conditions for a 6-month period. Stability studies of the dispersed microparticles were performed in order to evaluate the changes occurred in the diffusion of the drug to the suspending medium and in the dissolution behaviour during storage. The morphological alterations of the stored microcapsules were followed throughout the duration of the study by scanning electron microscopy. The polymer coatings of microcapsules prepared by the o/o method broke up on the first day of storage, while those made by the aqueous procedure remained intact during all the storage period. This agreed with the modification observed in the controlled-release profiles of terbutaline in the case of microcapsules prepared by the o/o method, which completely changed after the first week of storage. On the contrary, the microcapsules prepared by the aqueous method showed identical controlled-release profiles for all the stability study. The different behaviour of both types of microcapsules was attributed to the swelling suffered by the resin particles in contact with the aqueous suspending medium, which was higher in the microcapsules prepared by the o/o technique. In fact, in the anhydrous procedure, the microencapsulation was carried out on the shrunken resin particles, whereas in the o/w method, the presence of water during the microencapsulation process allowed the coating of the swollen particles, thus avoiding the further problem of rupture of the polymer coating.