Desenvolvimento de formas farmacêuticas sólidas orais de Uncaria tomentosa com actividade antioxidante

摘要

Uncaria tomentosa is a plant widely used in Peru’s traditional medicine. Thedecoction of the vine is used traditionally for many different health problems.A decoction was made from the bark of Uncaria tomentosa.The phenolic profiles of decocto and bark were analysed using HPLC, with diode arraydetector. In both samples it was identified caffeic acid as the major constituent. It wasalso identified protocatechuic acid, catechin and epicatechin. There was also thepresence of a large number of compounds with characteristic profile of 3-flavanols,possibly proanthocyanidines.For comparative purposes aqueous dried extract, Uncaria tomentosa barks, andalso a commercial extract of this plant were monitored for their antioxidant properties,against DPPH. The lyophilised aqueous extract of Uncaria tomentosa barks was themore active. This was also the extract with a high content of proanthocyanidins,determined through the vanillin method. These results support previous studies thatsuggest the importance of proanthocyanidins in the extract antioxidant potential.Antioxidants play a significant role in the pathogenesis of many diseases. One ofthe goals of this study was to get a pharmaceutical form with both antioxidant activityand high proanthocyanidins content. Early studies in vitro demonstrated thatprocyanidin oligomers are hydrolysed to mixtures of monomers and dimers in gastricmilieu. Since the absorption of monomers and dimers in the small intestine it’s easierthan proanthocyanidins with high molecular weight, it seemed preferable to select apharmaceutical form of conventional release.The success of a pharmaceutical form depends on the careful selection of theexcipients used, because the incompatibility between a drug and its excipients canchange its stability and bioavailability, influencing its effectiveness and safety. In orderto select pharmaceutical forms were carried out compatibility studies between Uncariatomentosa extracts and different excipients using differential scanning calorimetry(DCS) and tests of dissolution in simulated gastric juice, at 37 ºC, with 100 revolutionsper minute. The results obtained allow to select two formulations of dried extractprepared in accordance with the traditional methodology: capsules containing aqueousdried extract and sprayed Uncaria tomentosa barks (50 mg and 336,7 mg, respectively),without any excipients; capsules with dried extract (100 mg) and the excipientsselected; corn starch 10%, lactose 20% and microcrystalline cellulose 10%. Theseformulations were in accordance with the requirements for quality: tests of mass trialsuniformity, and of content uniformity.Dissolution tests were also conducted with commercial extract (with starch as anexcipient) and a presentation form available on the market, containing only powederedbark, named uncária Naturmil®. All the formulations were within the parameters ofquality defined: at least 85% of drug released at first 60 minutes.In order to compare the antioxidant activity of pharmaceutical forms developedwith other already marketed, the DPPH test was optimised to the new experimentalconditions: samples solubilized in simulated gastric juice.The determination of antioxidant activity in all formulations suggests that thereis also in gastric juice, a relationship between the content in proantocianidinas andantioxidant activity, since the formulations with dried extract, evidencing increasinglevels of procyanidins had an antioxidant activity significantly higher than otherformulations.Taking into account the results obtained with a mixture of pulverized bark withdried extract, where the antioxidant activity in gastric juice decreases in a significantway, between 20 and 40 minutes, and the results from other studies which suggest thatthe antioxidant activity of higher molecular weight procyanidins is more effective thantheir monomeric procyanidins, it was also made a study in order to know the evolutionof polymerization degree of procyanidines, over time, by TLC. The results suggest thatthe mixture of dried extract and pulverized bark had lower molecular weightprocyanidins from 20 to 100 minutes, in simulated gastric fluid, which may be oneexplanation for its decrease in antioxidant activity over time.