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

Abstract

Uncaria tomentosa is a plant widely used in Peru’s traditional medicine. The decoction 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 array detector. In both samples it was identified caffeic acid as the major constituent. It was also identified protocatechuic acid, catechin and epicatechin. There was also the presence of a large number of compounds with characteristic profile of 3-flavanols, possibly proanthocyanidines. For comparative purposes aqueous dried extract, Uncaria tomentosa barks, and also a commercial extract of this plant were monitored for their antioxidant properties, against DPPH. The lyophilised aqueous extract of Uncaria tomentosa barks was the more active. This was also the extract with a high content of proanthocyanidins, determined through the vanillin method. These results support previous studies that suggest the importance of proanthocyanidins in the extract antioxidant potential. Antioxidants play a significant role in the pathogenesis of many diseases. One of the goals of this study was to get a pharmaceutical form with both antioxidant activity and high proanthocyanidins content. Early studies in vitro demonstrated that procyanidin oligomers are hydrolysed to mixtures of monomers and dimers in gastric milieu. Since the absorption of monomers and dimers in the small intestine it’s easier than proanthocyanidins with high molecular weight, it seemed preferable to select a pharmaceutical form of conventional release. The success of a pharmaceutical form depends on the careful selection of the excipients used, because the incompatibility between a drug and its excipients can change its stability and bioavailability, influencing its effectiveness and safety. In order to select pharmaceutical forms were carried out compatibility studies between Uncaria tomentosa extracts and different excipients using differential scanning calorimetry (DCS) and tests of dissolution in simulated gastric juice, at 37 ºC, with 100 revolutions per minute. The results obtained allow to select two formulations of dried extract prepared in accordance with the traditional methodology: capsules containing aqueous dried extract and sprayed Uncaria tomentosa barks (50 mg and 336,7 mg, respectively),without any excipients; capsules with dried extract (100 mg) and the excipients selected; corn starch 10%, lactose 20% and microcrystalline cellulose 10%. These formulations were in accordance with the requirements for quality: tests of mass trials uniformity, and of content uniformity. Dissolution tests were also conducted with commercial extract (with starch as an excipient) and a presentation form available on the market, containing only powedered bark, named uncária Naturmil®. All the formulations were within the parameters of quality defined: at least 85% of drug released at first 60 minutes. In order to compare the antioxidant activity of pharmaceutical forms developed with other already marketed, the DPPH test was optimised to the new experimental conditions: samples solubilized in simulated gastric juice. The determination of antioxidant activity in all formulations suggests that there is also in gastric juice, a relationship between the content in proantocianidinas and antioxidant activity, since the formulations with dried extract, evidencing increasing levels of procyanidins had an antioxidant activity significantly higher than other formulations. Taking into account the results obtained with a mixture of pulverized bark with dried extract, where the antioxidant activity in gastric juice decreases in a significant way, between 20 and 40 minutes, and the results from other studies which suggest that the antioxidant activity of higher molecular weight procyanidins is more effective than their monomeric procyanidins, it was also made a study in order to know the evolution of polymerization degree of procyanidines, over time, by TLC. The results suggest that the mixture of dried extract and pulverized bark had lower molecular weight procyanidins from 20 to 100 minutes, in simulated gastric fluid, which may be one explanation for its decrease in antioxidant activity over time.