ABSTRACTChlorogenic and caffeic acids are bioactive phenolic compounds present in Cecropia glaziovii Snethl., Urticaceae, products that have been used as analytical markers. This paper reports a chemometric study aimed at improving chromatographic performance for quantification of these markers by RP-HPLC. The organic to aqueous content ratio, the acid content of the mobile phase, and the elution method were analyzed using a Response Surface Methodology IV-Optimal design. The resolution between peaks, retention time, tailing and retention factors, number of theoretical plates and peak widths were evaluated. The optimized conditions were mathematically determined as (A) trifluoroacetic acid 0.05% (v/v), (B) 12% (v/v) acetonitrile and (C) increasing gradient. The method was considered specific, fast, precise, reliable and linear in the ranges of 1.0–200.0 and 2.5–100.0 µg/ml for the chlorogenic and caffeic acids, respectively. The adequate conditions to separate and quantify both phenolic acids in C. glaziovii products were demonstrated. Satisfactory resolution was achieved when compared to a previously published chromatographic method which is unable to separate the chlorogenic acid and an interfering compound presented under certain extractive conditions, demonstrating the importance of systematic studies, specifically when analyzing complex plant matrices.

ABSTRACTThe aim of this study is to investigate the effect of Cecropia glaziovii Snethl, Urticaceae, extracts on the oral glucose tolerance curve, on glycemia in alloxan-induced diabetic rats and vasorelaxant effect after the extraction process, and to standardize the extractive solutions. The effects of the process variables and their interactions were calculated in relation to dry residue, pH, total phenolic results and chemical marker content. Furthermore, the effect of the extracts (400 mg/kg), chlorogenic (2 or 15 mg/kg) and caffeic acids (2 mg/kg) were investigated on the oral glucose tolerance curve and on glycemia in alloxan-induced diabetic rats. Oral administration of ethanol extracts 4d20 and 8d20 significantly improved glucose tolerance in the hyperglycemic rats. Chlorogenic and caffeic acids, as well as the association of the compounds were able to significantly reduce glycemia after oral gavage treatments. On the other hand, the aqueous extracts did not alter the glycemia. The aqueous extracts (8020 and 9030) and only the higher dose of chlorogenic acid presented a significant effect on serum glucose lowering in diabetic rats. Additionally, the IC50 reveals that the ethanol extracts presented more potent vasodilator effects than the aqueous extracts in aortic rings. This study shows that C. glazioviistandardized extracts exhibits antihyperglycemic action, is able to improve glucose tolerance and has a potent vascular relaxing effect. These results are probably linked to concentrations of the main phenolic compounds of the extracts.

Cecropia glaziovi Snethl., Urticaceae, is commonly used in South America and is one of the species included in the Brazilian Medicinal Plants Research Program. Pharmacological studies have led to reports of the potential of C. glaziovi as a hypotensive, antiasthmatic and anxiolytic agent. The strict requirements regarding the quality, safety and effectiveness of phytopharmaceutical products represent an enormous challenge in the search for products with a high level of uniformity, reproducibility and stability. The incorporation of dry extracts into multiparticulate dosage forms, such as pellets produced by extrusion/spheronization technology, is a suitable alternative to overcome the lack of technological properties of dry extracts, since they are associated with low flowability and high hygroscopicity. In this study, an optimized dry extract (ODE) of C. glaziovi was incorporated into pellets seeking to decrease the moisture sorption and increase the stability, safety and percentage of the extract in the final product. Pellets containing around 50% of ODE were considered the most technologically viable, offering a narrow particle size distribution, significant improvement in the flowability and compressibility properties, and decrease in the moisture compared with the ODE. In conclusion, pellets containing a high dose of the C. glaviovi extract were successfully prepared, achieving degrees of quality, physical stability and feasibility compatible with the desirable characteristics of a phytopharmaceutical.

Glóbulos, comprimidos e tabletes são formas farmacêuticas sólidas utilizadas em homeopatia. Constatam-se divergências entre técnicas de preparação descritas nos compêndios oficiais, bem como em farmácias homeopáticas. A dificuldade de padronização na impregnação destas formas farmacêuticas também ocorre devido à falta de detalhamento das técnicas na literatura existente, deixando para cada farmácia a escolha de como executá-las. O objetivo foi otimizar a técnica de impregnação, através do estudo de variáveis que interferem na impregnação de glóbulos, comprimidos e tabletes, aplicando como ferramenta estatística planejamento fatorial. As variáveis foram forma farmacêutica, percentual e tipo de impregnação e temperatura de secagem, sendo o ganho de massa, tempo de desintegração, friabilidade e dureza as variáveis dependentes. Para os glóbulos, observou-se maior ganho de massa quando impregnados a 10% e secagem realizada a 20 ºC. Para os tabletes e comprimidos, constatou-se maior ganho de massa quando impregnados a 15%, sendo que não houve diferença na impregnação simples ou tríplice nem nas diferentes temperaturas de secagem. Os resultados obtidos podem contribuir para a melhoria da qualidade do produto final, além de auxiliar no estabelecimento de técnicas padronizadas para os compêndios oficiais.

Globules, compressed tablets and tablet triturates are solid dosage forms used in homeopathy. Divergences can be noted between the preparation techniques described in official compendiums as well as those applied in homeopathic pharmacies. The difficulty associated with standardization of the impregnation of these dosage forms occurs due to the lack of detail provided for the techniques in the literature, leaving it up to each pharmacy to decide on the exact method of preparation. The objective was to optimize the impregnation technique, through investigating the variables that influence the impregnation of globules, compressed tablets and tablet triturates, applying the statistical tool of factorial design. The independent variables were the dosage form, percentage and type of impregnation and drying temperature, and the dependent variables were the mass gain, disintegration time, friability and hardness. For the globules, the greatest mass gain was for 10% impregnation and drying at 20 ºC. For the tablet triturates and compressed tablets the greatest mass gain was for 15% impregnation and there was no difference between the results obtained using simple and triple impregnation or different drying temperatures. The results can contribute to improving the final product quality, besides aiding in the establishment of standardized techniques for the official compendiums.

Glóbulos são uma das formas farmacêuticas mais dispensadas em farmácias homeopáticas no Brasil. Este trabalho teve como objetivo comparar técnicas de impregnação especificadas na Farmacopéia Homeopática Brasileira 2ª Edição e Manual de Normas Técnicas para Farmácia Homeopática 3ª Edição e na prática em farmácias homeopáticas do município de Florianópolis, Santa Catarina, Brasil. As variáveis de formulação percentual de insumo ativo (3 e 10%) e tipo de impregnação (simples e tríplice) e a variável de processo temperatura de secagem (20 e 50ºC) foram analisadas através de planejamento fatorial 2³. As respostas estudadas foram o peso antes e após impregnação e o tempo de desagregação. Os resultados mostraram maior diferença de peso com impregnação a 10 % e secagem a 50ºC, independente do tipo de impregnação. O tempo de desagregação não foi influenciado pelas variáveis em estudo (p < 0,05). Verificou-se melhor homogeneidade para a formulação com impregnação tríplice a 10%.

Globules are one of the most dosage forms dispensed in homeopathic pharmacies in Brazil. This work aimed at comparing different impregnation techniques specified in the Brazilian Homeopathic Pharmacopoeia 2 Edition and Manual of Technical Norms for Homeopathic Pharmacy 3 Edition and the practical in homeopathic pharmacies in the city of Florianópolis, state of Santa Catarina, Brazil. The formulations variables percent active raw material (3 and 10%), impregnation type (simple and triple) and the process variable drying temperature (20 and 50ºC) were analyzed through a factorial design 2³. The studied answers were the weight before and after the impregnation and time of disaggregation. The results show a larger weight difference with the 10% impregnation and the drying of 50ºC, regardless of the impregnation type. The time of disaggregation wasn't influenced by the studied variables (p < 0.05). The best homogeneity was verified for the formulation with triple impregnation at 10%.