Formas farmacéuticas y microencapsulación para la administración oral de probióticos

Resumen

This thesis has been developed within the Andalusian Research Group CTS-205 ¿Practical pharmaceutics¿ in collaboration with NIZO Food Research (Ede, The Netherland). One of the research lines of the group CTS-205 is the development of different dosage forms and particles for the administration of probiotics. Specifically, this thesis has been focused in the preparation and characterization of microparticles for the protection of Lactobacillus fermentum CECT 5716 and Lactobacillus plantarum WCSF1. Furthermore, preparation of tablets for the administration of L. fermentum CECT5716 was also performed. With these aims, different encapsulation technologies used with probiotics were firstly reviewed. Then, internal gelation technology was selected for the microencapsulation of L. fermentum CECT 5716. Results show that these particles were able to partially protect bacteria during one month at 4 ºC. In the case of L. plantarum WCSF1, spray dried technology using different carriers was tested. The protection provide by the carriers was insufficient. However the selected food matrix (infant formula) seems to be adequate as a result of its low moisture content. Concerning oral solid dosage forms, different gastro-resistant tablets were developed. The selected material was compatible with probiotic. Viability of probiotics after technological process was 10% which allow to obtain tablets with 109 ufc, concentration that meets the objective for this kind of pharmaceutical forms. Tablets also meet the quality criteria required by the United States Pharmacopeia and Spanish Pharmacopeia referring to friability and disintegration test. Protection of probiotics through passage to the stomach and delivery of probiotic in the intestine were verified. The best viability after simulated stomach pH was for Eudragit® L100- sodium alginate tablets. These tablets were found to be stable over a 6 months period when stored at 4ºC. However, at room temperature tablets started to lose viability after 3 months. As a whole, the results of the present work provide evidence that probiotics can be protected by microencapsulation to be included in food and pharmaceutical matrices, but not all microencapsulation techniques are suitable. Internal gelation with alginate and starch has shown to be suitable, at least for L.fermentum CECT5716. Controlled-release tablets are suitable pharmaceutical forms for the administration of probiotics. Further studies are needed to analyze the behavior of microencapsulated probiotics into food matrices and to prove the effects of these formulations in vivo.