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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.

En medicina popular, Silybum marianum se usa como agente hepatoprotector. La silimarina es su componente principal. El presente trabajo trata de la formulación y evaluación de tabletas de S. marianum a partir de extracto etanólico por compresión directa. El extracto etanólico se obtuvo de las semillas mediante extracción con soxhlet. Se prepararon dos formulaciones farmacéuticas usando extracto fluido como principio activo y Aeroperl® 300 Pharma como vehículo. Para mejorar la capacidad de flujo y la compresibilidad, se emplearon excipientes coprocesados MicroceLac® 100 y FlowLac® 90. Los parámetros de precompresión y postcompresión se evaluaron de acuerdo con USP 34-NF 29. Además, la silimarina se determinó mediante datos espectrales de RMN. Ambas formulaciones mostraron excelentes propiedades reológicas y los mejores parámetros biofarmacéuticos se observaron en F2 (S. marianum ethanolic extract, aeroperl® 300 Pharma, flowLac® 90, glicolado de almidón y estearato de magnesio) en términos de friabilidad (0,82%) y el tiempo de desintegración (8,05 min). In popular medicine Silybum marianum is used as a hepatoprotective agent. Silymarin is the major constituent. The present work deals with the formulation and evaluation of S. marianum tablets from ethanolic extract by direct compression. The ethanolic extract was obtained from seeds by soxhlet extraction. Two pharmaceutical formulations were prepared using fluid extract as an active principle, and Aeroperl® 300 Pharma as a carrier. In order to improve flow ability and compressibility, co-processed excipients MicroceLac® 100 and FlowLac® 90 were employed. Pre-compression and post-compression parameters were evaluated according to USP 34-NF 29. Besides, silymarin was determined by NMR spectral data. Both formulations showed excellent rheological properties and the best biopharmaceutical parameters were observed in F2 (S. marianum ethanolic extract, aeroperl® 300 Pharma, flowLac® 90, glycolate starch and magnesium stearate) in terms of the friability (0.82 %) and the disintegration time (8.05 min). Fil: Cianchino, Valeria Andrea. Universidad Nacional de San Luis; Argentina Fil: Favier, Laura Silvina. Universidad Nacional de San Luis; Argentina Fil: Ortega, Claudia Alicia. Universidad Nacional de San Luis; Argentina Fil: Peralta, Cecilia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina Fil: Cifuente, Diego Alberto. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina

In the present work we investigated, for the first time, the anti-inflammatory activity and the antioxidant properties ofaqueous and ethanolic extracts, obtained from stem bark of Geoffroea decorticans (Gill. ex Hook. et Arn.) Burk. (Fabaceae). G.decorticans, commonly known as ?chañar? or ?chañarcillo?, is a traditional argentinean plant used as emollient, balsamic, antitussive,expectorant and anti-inflammatory. The stem bark was collected from San Francisco del Monte de Oro, San Luis, Argentina.Anti-inflammatory activity was evaluated by carrageenan-induced paw edema in rats. Antioxidant activity was tested using1,1-Diphenyl-2-picrylhydrazyl radical-scavenging activity (DPPH), 2,2´-Azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radicalscavenging activity (ABTS) and ferric ion-reducing power (RP-Fe) assays. Aqueous extract 10% p/v showed anti-inflammatory activity (3h, 48% inhibition, 5h 37% inhibition and 7h 17% inhibition) and antioxidant activity (DPPH, IC50 (mg/mL) = 0.098 ± 0.032; ABTS, IC50 (mg/mL) = 0.022 ± 0.343, RP-Fe IC50 (mg/mL) = 1.124 ± 0.146). In the other hand, the ethanolic extract 5% p/v, presented anti-inflammatory activity (3h, 34% inhibition, 5h 38% inhibition and 7h 35% inhibition) and antioxidant activity (DPPH, IC50 (mg/mL) = 0.133 ± 0.027; ABTS, IC50 (mg/mL) = 0.086 ± 0.262, RP-Fe IC50 (mg/mL) = 7.089 ± 0.104). These results suggest that, also fruits, the aqueous and ethanolic extracts from the stem bark of G. decorticans present significant anti-inflammatory activity and antioxidant properties. Fil: Jofré, Mariana. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Fusco, María. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Favier, Laura. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química. Area de Química Orgánica; Argentina Fil: Teves, Mauricio. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Rotelli, Alejandra Ester. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Pedernera, Ana. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Pelzer, Lilian. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Ortega, Claudia. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina Fil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Farmacia. Area de Farmacognosia; Argentina

Forty four extracts from nine Baccharis spp. from the Caulopterae section were tested in combination with terbinafine against Trichophyton rubrum with the HTSS assay at six different ratios with the aim of detecting those mixtures that produced a ≥50%statistically significant enhancement of growth inhibition. Since an enhanced effect of a combination respective of its components, does not necessarily indicate synergism, three-dimensional (3D) dose–response surfaces were constructed for each selected pair of extract/antifungal drug with the aid of CombiTool software. Ten extracts showed synergistic or additive combinations which constitutes a 22% hit rate of the extracts submitted to evaluation. Four flavonoids and three ent-clerodanes were detected in the active Baccharis extracts with HPLC/UV/ESI-MS methodology, all of which were tested in combination with terbinafine. Results showed that ent-clerodanes but not flavonoids showed synergistic or additive effects. Among them, bacchotricuneatin A followed by bacrispine showed synergistic effects while hawtriwaic acid showed additive effects. Fil: Rodriguez, María Victoria. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ivancovich, Juan J.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Pellegrino, Jose Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina Fil: Favier, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina Fil: Raimondi, Marcela P.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Gattuso, Martha Ana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers. These molecules could be effective in the treatment of human diseases associated with inappropriate mast cell activation.

The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of the above lactones to stabilize mast cells. The comparative study with ketotifen and sodium chromoglycate, well known mast cell stabilizers, showed the following order of potency dehydroleucodine=xanthatin>3-benzyloxymethyl-5H-furan-2-one> or =ketotifen/sodium chromoglycate to inhibit mast cell serotonin release induced by compound 48/80. The present study provides the first strong evidence in favour of the hypothesis that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit compound 48/80-induced serotonin release from peritoneal mast cells, acting thus as mast cell stabilizers. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response.

The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58–96% at a dose from 12.5 to 100 mg/kg. These results appear to confirm that the presence of a non-hindered α,β-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.

Two new diterpenes and four known flavones were isolated from the aerial parts of Ophryosporus charrua (Griseb. Hieron. The diterpenes were characterized as 2-oxo-3α-hydroxy- ent -labd-7-en-15-oic acid and 2-oxo- ent -haliman-1(10), 7-dien-15-oic acid. The structures were established by analyses of their 1 H and 13 C NMR spectra with the aid of 2D experiments and chemical transformations. The flavones were identified as apigenin-7,4′-dimethyl ether, circimaritine, salvigenin, and 7- O -methyleriodictyol. © 1997 Elsevier Science Ltd. All rights reserved

From the aerial parts of Conyza sophiaefolia a new alicyclic furan diterpene was isolated and characterized as an E-isomer in C6 of centipedic acid. In addition, the new clerodane type diterpene 12-epi-bacchotricuneatin A as well as two known related diterpenoids were identified. The flavone apigenine was also isolated. Structures were determined on the basis of spectroscopic evidence.

Seven acetophenone derivatives were isolated from the aerial parts of Ophryosporus axilliflorus (Griseb.) Hieron. These compounds were subjected to the carrageenan-induced mouse paw edema test where tremetone (7) showed extremely anti-inflammatory activity. Furthermore, the non-benzofuran acetophenones 5 and 6, showed a significant response.

Growth-inhibitory activities of selected natural benzofurans (4-9), trans-cinnamic acid derivatives (10-13), chromene compounds (14 and 16), and some semisynthetic derivatives were determined in last instar larvae of Tenebrio molitor via topical administration in Me2CO. The most inhibitory of the tested compounds were 3-gamma, gamma-dimethylallyl-p-coumaric acid (10) and the benzofuran derivative 12-(p-cumaroyloxy)-tremetone (5), the former compound acting on the pupae and the latter on the last instar larvae. Several developmental deficiencies were observed, and some structure-activity relationships are discussed.

From the aerial parts of Laennecia sophiifolia (Kunth) G.L. Nesom, a neo-clerodane and an acyclic furano diterpene were isolated, along with four known compounds, 2beta-hydroxyhardwickiic acid, hawtriwaic acid, apigenin, and beta-sitosterol. Their structures were established as 12-epi-bacchotricuneatin A and (2E,6E)-9-(3-furyl)-6-methyl-2-(4-methylpent-3-enyl)-nona-2,6-dienoic acid, by analysis of spectral evidence. The absolute structure of 12-epi-bacchotricuneatin A was determined by a circular dichroism spectral comparison with that of bacchotricuneatin A.

From the aerial parts of Laennecia sophiifolia (Kunth) G.L. Nesom, a neo-clerodane and an acyclic furano diterpene were isolated, along with four known compounds, 2β-hydroxyhardwickiic acid, hawtriwaic acid, apigenin, and β-sitosterol. Their structures were established as 12-epi-bacchotricuneatin A and (2E,6E)-9-(3-furyl)-6-methyl-2-(4-methylpent-3-enyl)-nona-2,6-dienoic acid, by analysis of spectral evidence. The absolute structure of 12-epi-bacchotricuneatin A was determined by a circular dichroism spectral comparison with that of bacchotricuneatin A.