Banca de QUALIFICAÇÃO: TARCÍSIO CÍCERO DE LIMA ARAÚJO

DEVELOPMENT OF A PHARMACEUTICAL FORM WITH THE ASSOCIATION OF EXTRACT FROM THE ROOTS OF 

Cannabis sativa L. WITH MEPHENAMIC ACID AND EVALUATION OF ITS ACTIVITY IN RODENTS UTERUS

Marijuana; Root; NSAIDs; Physical-chemical analysis; Analytical techniques; Pharmaceutical form; Quality control; Uterine disorders.

Popularly known as marijuana, Cannabis sativa has, among other properties, anti-inflammatory, analgesic, antipyretic and acts on the respiratory and digestive systems. The root of C. sativa is a part of the plant that is still little explored and discussed. There have been mentions of its medicinal use in the São Francisco Valley region in the northeastern hinterland as an anti-inflammatory, antiasthmatic and antidysmenorrheal agent. The aim of this study was to develop a pharmaceutical form based on the association, in sub-doses, of the aqueous extract of C. sativa L. roots (EAqCs) with mefenamic acid (MA) and to evaluate its activity in the uterus of rodents. Initially, thermal and chemical analyses of the EAqCs and AM were carried out using methods of characterization and identification of constituents by analytical techniques such as thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), high-performance liquid chromatography coupled to diode array detector or mass spectrometry (HPLC-DAD-MS). The particle size results of the materials showed that EAqCs can be classified as a semi-fine powder, as well as MA (300 and 250 µm, respectively). TG analysis revealed a similar thermal behavior and degradation profile for the materials under study. Both showed two thermal events in the TG, corresponding to loss of moisture and thermal decomposition, while AM showed an additional thermal event in the derivative thermogravimetry, corresponding to loss of organic matter. AM was subjected to DSC analysis, confirming the crystalline structure of the compound and its degree of purity. In the FTIR, bands of interest were identified which correspond to the chemical groups present in the molecular composition of EAqCs and AM, contributing to structural elucidation studies. In the HPLC-DAD, a selective analytical method was developed for the analysis of EAqCs, confirming the presence of N-trans-feruloiltyramine and identifying and quantifying p-coumaric acid for the first time in the roots of C. sativa from northeastern Brazil. In addition, the method enabled the chromatographic profile of AM to be obtained and a chromatographic peak characteristic of pure substances to be observed. From the analysis by HPLC-MS, four chemical constituents were identified in EAqCs, two of which were confirmed in the analysis of spectral families in the GNPS software. The prospects are to develop a safe pharmaceutical form based in the association of EAqCs and mefenamic acid, in sub-doses, with subsequent stability tests and quality control of the formulation obtained, subjecting it to the process of dosing by CLAE-DAD of the bioactive markers. Subsequently, it is hoped to conduct single and repeated dose toxicity studies of the pharmaceutical form and evaluate its pharmacological effect on the uterus of rodents. Thus, the data on the characterization and identification of constituents in these extracts are essential for obtaining chemical markers, which should be used in the quality control analyses of formulations obtained from plant raw materials, with the aim of contributing to the literature and providing data to assist in the future development of new drugs from the roots of C. sativa, with safety and efficacy against uterine disorders in rodents.