Gastroresistant microspheres for the oral administration of bromelain.

Purpose. To develop gastroretentive microspheres for the oral administration of bromelain (BRO). Methods. Microspheres containing BRO were prepared with two different polymers, i.e. chitosan (CHI) and Eudragit® L 100 (EuL100). CHI-based microspheres were prepared by emulsification of an aqueous solution of BRO in paraffin, followed by cross-linking with Na2SO4 and solvent evaporation under nitrogen. The EuL100-based microspheres were prepared by dispersing solid BRO in a organic solution containing the polymer. The resulting suspension was then dispersed in paraffin oil to form a solid-in-oil-in-oil dispersion and the solvent was then evaporated under stirring. The microspheres were characterized in terms of dimensions, morphology, BRO actual loading and photolytic activity of the encapsulated BRO. In the case of CHI-based microspheres, release studies were evaluated in HCl 0.1N, in intestinal simulated fluid (SIF) and in rat cecal content (CCR). In vitro studies of BRO from the EuL100-based microspheres were investigated in PBS at different pH (i.e. 3.0, 6.8 and 7.2). Results. We prepared CHI-based microspheres characterised by mean diameter of 17.7 microm ± 9.1, and with an BRO encapsulation efficiency of 99.3 ± 1.5%. The proteolitic activity assay demonstrated that the BRO was encapsulated in its active form. However, the in vitro release studies showed absence of BRO release upon microsphere incubation in HCl 0.1 N, in SIF ed in CCR. In the case of the EuL100, we obtained microspheres with a mean diameter of 254 microm ± 47.4, with a BRO encapsulation efficiency of 87.0 ± 2.0%. In the in vitro release studies, BRO release from microspheres was not observed at pH 3.0, while a fast BRO release was obtained at pH 6.8 e 7.2. Conclusions. The EuL100-based microspheres have showed the release properties suitable to be used in the following in vivo experiments on rats.