Desenvolvimento de pellets mucoadesivos contendo pectina de solanum lycocarpum st. hill tiolada

Abstract

The development of mucoadhesive systems can facilitate control of inflammatory bowel diseases by increasing local drug bioavailability. Pectin, a first generation mucoadhesive natural polymer, when subjected to the thiolation reaction is more mucoadhesive by the insertion of thiol groups to their structure. In particular, pectin extracted from Solanum lycocarpum St. Hill (lobeira) has interesting properties for pharmaceutical use. In this work, citrus pectin and pectin extracted from Solanum lycocarpum were chemically modified by reaction with thioglycolic acid and characterized by molecular weight and amount of thiol groups. Furthermore, ketoprofen pellets containing natural or thiolated pectins were developed by extrusion and spheronization technique, and subsequently the mucoadhesion evaluated in intestinal porcine ex vivo model. The molecular weights of citrus pectin (121 kDa) and pectin extracted from S. lycocarpum (57.5 kDa) were increased after thiolation reaction (thiolated citrus pectin 137 kDa and pectin extracted from S. lycocarpum, 64.5 kDa). In addition to molecular weight, the degree of methoxylation of different pectins (68% and 35% for citrus pectin and extracted from S. lycocarpum, respectively) exerted influence on the conditions necessary for the satisfactory development of the pellets.The two thiolated pectins presenteds 0.69 mM thiol / g polymer groups. For the development of ketoprofen pellets containing citrus pectin it was necessary to add PVP K-30 in the wetting liquid, resulting in the formation of spherical products (projected spherical shape; sphericity of 0.83). The pellets were obtained with ratio of wetting liquid: solid of 1: 1. The pellets containing other pectins were developed based on the formulation containing citrus pectin. For those containing thiolated citrus pectin the ratio of wetting liquid: solid necessary for obtaining spherical pellets of appropriate size was 0.75: 1. The pellets containing pectin extracted from S. lycocarpum required smaller amount of wetting liquid (0.5: 1), very probably due to higher solubility of this polymer in water. The pellets containing the thiolated pectin extracted S. lycocarpum showed the same behavior of their peers not thiolated.The mucoadhesion testing of the pellets showed time increased adherence onto porcine mucosa when unmodified pectin S. lycocarpum was incorporated, which shows the highest adhesive strength of this material when compared with citrus pectin. The thiolation of pectins significantly increased mucoadhesion of the pellets with remaining 60% of the units on the membrane surface after 480 minutes of testing. There was no statistical difference between the pellets containing thiolated citrus pectin and thiolated pectin from S. lycocarpum. The overall results showed that the pectin from S. lycocarpum showed favorable technological properties to obtain pellets by extrusion-spheronization process, and the pellets obtained were more mucoadhesive compared to pellets containing citrus pectin. Finally, the thiolation reaction proved to be an effective strategy to improve mucoadheviness of the pellets. Thus, it was concluded that the sustainable exploitation and utilization of the pectin from S. lycocarpum is a strategy with great economic and technological potential.