Development of tablets and isolation of secondary metabolites from hydroalcoholic extract of Copaifera langsdorffii Desf. leaves

Author(s)

Mauro Nogueira da Silva

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2011-08-29

Examining board members

Jairo Kenupp Bastos; Carmen Lúcia Cardoso; Osvaldo de Freitas

• Advisor: Jairo Kenupp Bastos

Abstract

Copaifera langsdorffii belongs to Leguminosae Juss. family, sub-family Caesalpinioideae Kunth. In Brazil, Copaifera species are widely spread in Amazonas, Pará and Ceará states and are worldwide known by the oil-resin that can be extracted from its trunk. This oleoresin and its volatile fractions have been studied by many research groups. However, few studies are related to the chemical and biological composition of other plant parts, such as leaves. We have been investigating the antilitiasic activity of the hydroalcoholic extract from C. langsdorffii, and it have risen the in both the phytochemical investigation of the aerial parts and the production of tablets with the obtained extract. Thus, the aim of this study was to evaluate the leaf extract chemical profile, to isolate and identify the secondary metabolites to be used as chromatographic standards, using different chromatographic methods, for the analysis of plant materials, its extracts and products, as well as, to carry out studies of extraction, drying and preformulation to produce tablets containing a suitable dose of the extract for using in future clinical trials. Chemical profile of the extract and its fractions obtained after partition with solvents with increasing polarity revealed that the extract is majorly composed by polar compounds. The ethyl acetate fraction was submitted to classical column chromatography and high speed countercurrent chromatography (HSCCC) techniques, resulting in isolation of compounds 1 (quercetin-3-O--L-rhaminopiranoside) and 2 (kaempferol-3-O--L-rhaminopiranoside, after preparative HPLC purification. The aqueous fraction was submitted to column chromatography techniques using gel filtration (sephadex LH-20) and HSCCC yielding compounds 3 to10, after preparative HPLC purification. Compounds 4, 6, 9 and 10 were identified as galloylquinic acid derivatives 6\',4\'\'-dimethoxy-3,4-di-O-galloylquinic acid; 6\'\'\'-methoxy-3,4,5-tri-O-galloilquinic acid; 4\',4\'\'\'-dimethoxy-3,4,5-tri-O-galloylquinic acid; and 4- methoxy-3-O- galloylquinic acid, respectively. Studies of extraction process furnished three extracts with higher yielding, using a simple extraction process with ethanol: water 7:3 (45 mL) with 3g of plant biomass, which was chosen to obtain the extract for drying studies. Drying results showed no significant differences between the undertaken experiments, and the dried extracts particles did not have good flow properties for direct compression. Wet granulation of dried extract containing 73% of plant extract, 25% of excipients Maltodextrin: Aerosil (1:1) and 2% of polyvinyl pyrrolidone produced particles with excellent flow properties for compression. Granulate compression without adding other excipients furnished tablets with high hardness and long disintegration times. However, granulates prior mixed with amide-lactose produced tablets with better physical properties, such as hardness and friability with acceptable values and adequate disintegration times. (AU)

• FAPESP's process: 09/10975-3 - Chemical markers isolation and development of a solid pharmaceutical formulation from the hydroalcoholic extract from the aereal parts of Copaifera langsdorffii
• Grantee: Mauro Nogueira da Silva
• Support Opportunities: Scholarships in Brazil - Master