Verbascoside, synthetic derivatives and other glycosides from Argentinian native plant species as potential antitumoral agents.

A phytochemical study was performed on three native plant species from the central-western zone of Argentina: Buddleja cordobensis Grisebach, Baccharis salicina Torr. & A. Gray and Nepeta cataria L. We could obtain verbascoside (1) from B. cordobensis. From N. cataria, we could obtain 1, 5, 9-epi-deoxyloganic acid (2) L. Finally, we could isolate 2-ß-(L-rhamnopyranosyl)-3-angeloyloxy-15-acetyloxy-7,13(14)-E-dien-ent-labdane (3) and 2-ß-(L-rhamnopyranosyl)-3-α-angeloyloxy-15-hydroxy-7,13(14)-E-dien-ent-labdane (4) from B. salicina. Moreover, three derivatives from 1, and one semi-synthetic derivative from 2, were prepared. PCR reaction was used to analyse the activity against DNA polymerase and cell culture to determine cytotoxicity and antitumoral activity. Verbascoside (1) was strongly active in the nanomolar scale (IC50 = 356 nM) against DNA polymerization. Moreover, verbascoside was also strongly active in the nanomolar scale against human melanoma cell line (IC50 = 256 nM) and human colorectal cell line (IC50 = 320 nM). Furthermore, derivatives 6 and 7 were cytotoxic against both cancer cell lines.

New Orodispersible Mini Tablets of Enalapril Maleate by Direct Compression for Pediatric Patients.

BACKGROUND: In many countries, hypertension in the pediatric population is considered a serious risk of mortality and morbidity. In this respect, it is central to design and develop new pharmaceutical forms for pediatric patients with hypertension. The development of Orodispersible Mini-Tablets (ODMTs) for pediatric use has gained importance in recent years. Therefore, regulations for developing suitable and palatable dosage forms for pediatric patients have been established by WHO authorities. OBJECTIVE: This study aimed to design and develop orodispersible mini tablets of enalapril maleate (EnM ODMTs) for pediatric use. METHODS: Five pharmaceutical formulations (A, B, C, D and E, shown in Table 1) were designed. The effects of different co-processed excipients and active pharmaceutical ingredients at different doses were studied. Lactose co-processed excipients selected were the following: Tablettose® 80, Microce- Lac® 100 and StarLac®. The micromeritic properties for all the physical mixtures were examined. The mini tablets were obtained by direct compression. Quality control parameters were determined in accordance with US Pharmacopeia. RESULTS: Three OMDTs with StarLac® showed good results of hardness, flow ability and fast disintegration. The formulation with 0.1 mg of enalapril maleate presented the best results for the official parameters of hardness (4.0 kp), friability (< 1%), disintegration time (28 s), drug content uniformity (103.6 %), and wetting time (23 s). CONCLUSION: The three OMDTs with StarLac® showed good quality parameters, according to official requirements. Formulation A exhibited the best wetting time, complying with the dose recommended for pediatric patients. This formulation could be considered eligible for being manufactured at industrial scale.

Analysis of potential adulteration in herbal medicines and dietary supplements for the weight control by capillary electrophoresis.

Four different phytopharmaceutical dosage forms for use in weight control programs were analyzed. Two different ground herbal blends and their correspondent infusions, a capsule and a tincture were investigated for the presence of compounds used as adulterants in these products. A capillary electrophoresis (CE) method was developed and validated. The optimized experimental conditions were: BGE, sodium tetraborate buffer 20mM, pH 9.2, voltage applied 30kV, capillary temperature 25°C, injection sample at 0.5Psi during 5s. Ephedrine, norephedrine, caffeine and furosemide were baseline separated in less than 7min; the migration times were found to be 2.65, 2.90, 3.75 and 6.58min, respectively. The analysis showed in sample 3 concentrations of 0.45±0.03mgg(-1) (ephedrine), 0.33±0.02mgg(-1) (norephedrine), 1.09±0.41mgg(-1) (caffeine) and 0.80±0.17mgg(-1) (furosemide). Caffeine content in samples 1, 2 and 4 was 0.61±0.06mgg(-1), 15.66±1.05mgg(-1) and 2.27±0.13mgml(-1), respectively. Linearity was obtained in the concentration range of 1-1000µgml(-1). Limits of detection (LOD) and quantification (LOQ) were determined as 0.42µgml(-1) and 1.40µgml(-1) (ephedrine), 0.47µgml(-1) and 1.40µgml(-1) (norephedrine), 0.12µgml(-1) and 0.48µgml(-1) (caffeine), 0.22µgml(-1) and 0.73µgml(-1) (furosemide). The common constituents of the samples did not interfere with the potential adulterants. Repeatability was better than 0.24% RSD for the retention time and 1.43% for the peak area. Intermediate precision was tested by changing the capillary, the day of operation and the operator, in all the cases the %RSD was better than 3.06.