http://sedici.unlp.edu.ar:80/handle/10915/228 Sun, 15 Nov 2026 08:10:22 GMT 2026-11-15T08:10:22Z http://sedici.unlp.edu.ar:80/handle/10915/7937 Comunicacion Latin American Journal of Pharmacy; vol. 29, no. 3 The present study deals with the amelioration by Delonix regia aerial parts extract against hepatotoxicity induced by carbon tetrachloride (CCl4), which was evaluated in terms of serum marker enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumine, total protein, direct bilirubine and total bilirubine. These biochemical parameters were alter by the single dose of CCl4 (2 ml/kg, p.o.). Pretreatment with D. regia extracts prior to administration of CCl4, at the dose of 400 mg/kg p.o. per day for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels. Silymarine was used as reference standard. Amongst all the fractions, ethyl acetate fraction showed best protective potential of D. regia aerial parts against hepatotoxicity. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7937 2010-01-01T00:00:00Z The present study deals with the amelioration by Delonix regia aerial parts extract against hepatotoxicity induced by carbon tetrachloride (CCl4), which was evaluated in terms of serum marker enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumine, total protein, direct bilirubine and total bilirubine. These biochemical parameters were alter by the single dose of CCl4 (2 ml/kg, p.o.). Pretreatment with D. regia extracts prior to administration of CCl4, at the dose of 400 mg/kg p.o. per day for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels. Silymarine was used as reference standard. Amongst all the fractions, ethyl acetate fraction showed best protective potential of D. regia aerial parts against hepatotoxicity. http://sedici.unlp.edu.ar:80/handle/10915/7936 Comunicacion Latin American Journal of Pharmacy; vol. 29, no. 3 Powder mixtures (1:1) of tibolone polymorphic forms I (monoclinic) and II (triclinic) and excipients have been prepared and compacted. The samples were stored at 50 °C and 90% RH for one month and subsequently were evaluated using differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC). The results indicate that during the compaction, the applied pressure reduced the chemical stability of tibolone in both polymorph forms. The triclinic form was more chemically unstable, both pure and in contact with excipients, than the monoclinic form. Lactose monohydrate was shown to reduce chemical degradation for both forms. Ascorbyl palmitate was shown to affect the tibolone stability differently depending on the polymorphic form used. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7936 2010-01-01T00:00:00Z Powder mixtures (1:1) of tibolone polymorphic forms I (monoclinic) and II (triclinic) and excipients have been prepared and compacted. The samples were stored at 50 °C and 90% RH for one month and subsequently were evaluated using differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC). The results indicate that during the compaction, the applied pressure reduced the chemical stability of tibolone in both polymorph forms. The triclinic form was more chemically unstable, both pure and in contact with excipients, than the monoclinic form. Lactose monohydrate was shown to reduce chemical degradation for both forms. Ascorbyl palmitate was shown to affect the tibolone stability differently depending on the polymorphic form used. http://sedici.unlp.edu.ar:80/handle/10915/7935 Comunicacion Latin American Journal of Pharmacy; vol. 29, no. 3 A simple procedure was described for the determination of Withanolide A and Withanolide B in Ashwagandha root by HPLC. Separation was achieved on a Spherisorb C18 column with Water: Acetonitrile in the gradient elution. Detection was accomplished with UV detection at λ = 216 nm. Using this method, the bioactive steroid in Withania somnifera was determined. Significant variations in the contents of Withanolide A and Withanolide B in Ashwagandha root growing in different locations were also observed. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7935 2010-01-01T00:00:00Z A simple procedure was described for the determination of Withanolide A and Withanolide B in Ashwagandha root by HPLC. Separation was achieved on a Spherisorb C18 column with Water: Acetonitrile in the gradient elution. Detection was accomplished with UV detection at λ = 216 nm. Using this method, the bioactive steroid in Withania somnifera was determined. Significant variations in the contents of Withanolide A and Withanolide B in Ashwagandha root growing in different locations were also observed. http://sedici.unlp.edu.ar:80/handle/10915/7934 Comunicacion Chemical composition and toxicity of essential oils of Piper spp. against larvae of Aedes aegypti L. (Diptera: Culicidae) Latin American Journal of Pharmacy; vol. 29, no. 3 Aedes aegypti L. é um dos vetores do dengue. No Brasil, tem ganhado muita atenção no setor da saúde pública, uma vez que esta doença tem se tornando mais agressiva na forma hemorrágica na popula- ção. Esse estudo teve como objetivo investigar o efeito de óleos essenciais de Piper aduncum, Piper marginatum e Piper nigrum contra larvas de Aedes aegypti. Em um esforço para encontrar uma maneira natural, eficaz e acessível para controlar esta doença endêmica, as atividades dos óleos essenciais, a partir das plantas, foram analisadas por comparação através da medida da CL₅₀ . Os óleos essenciais obtidos por hidrodestilação foram analisados por CG/EM. Os principais componentes identificados foram: β-pineno (32,7%) e E-cariofileno (17,1%) em P. aduncum; isoelemecina (21,7%) e apiol (20,1%) em P. marginatum e E-cariofileno (24,2%) e Óxido-cariofileno (20,1%) em P. nigrum. Os resultados mostram que Piper marginatum apresentou CL50 de 8,29 μg/mL e este trabalho é o primeiro relato de atividade larvicida de P. aduncum. Estes resultados sugerem que os óleos essenciais de espécies do gênero Piper são promissores como larvicidas contra larvas de A. aegypti.; Aedes aegypti L. is one of the vectors of dengue fever. In Brazil it has gain much attention in the Public Health sector since this disease has becoming more aggressive in the hemorrhagic form in the population. This study aimed to investigate the effect of Piper aduncum, Piper marginatum and Piper nigrum essential oils against Aedes aegypti larvae. In an effort to find a natural effective and affordable way to control this endemic disease, the larvicidal activities of essential oils from the plants were analyzed for activity comparison by measurement of their LC₅₀ . The essential oils isolated by hydrodistillation were analyzed by GC/MS. The main components identified were: β-pinene (32.7%) and E-caryophyllene (17.1%) in P. aduncum; isoelemecin (21.7%) and apiole (20.1%) in P. marginatum and E-caryophyllene (24.2%) and caryophyllene oxide (20.1%) in P. nigrum. The results show that Piper marginatum presented the LC50 of 8.29 μg/mL and these are the first report about the larvicidal activity of P. aduncum. These results suggest that the essential oil of Piper species are promising as larvicide against A. aegypti larvae. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7934 2010-01-01T00:00:00Z Aedes aegypti L. é um dos vetores do dengue. No Brasil, tem ganhado muita atenção no setor da saúde pública, uma vez que esta doença tem se tornando mais agressiva na forma hemorrágica na popula- ção. Esse estudo teve como objetivo investigar o efeito de óleos essenciais de Piper aduncum, Piper marginatum e Piper nigrum contra larvas de Aedes aegypti. Em um esforço para encontrar uma maneira natural, eficaz e acessível para controlar esta doença endêmica, as atividades dos óleos essenciais, a partir das plantas, foram analisadas por comparação através da medida da CL₅₀ . Os óleos essenciais obtidos por hidrodestilação foram analisados por CG/EM. Os principais componentes identificados foram: β-pineno (32,7%) e E-cariofileno (17,1%) em P. aduncum; isoelemecina (21,7%) e apiol (20,1%) em P. marginatum e E-cariofileno (24,2%) e Óxido-cariofileno (20,1%) em P. nigrum. Os resultados mostram que Piper marginatum apresentou CL50 de 8,29 μg/mL e este trabalho é o primeiro relato de atividade larvicida de P. aduncum. Estes resultados sugerem que os óleos essenciais de espécies do gênero Piper são promissores como larvicidas contra larvas de A. aegypti. Aedes aegypti L. is one of the vectors of dengue fever. In Brazil it has gain much attention in the Public Health sector since this disease has becoming more aggressive in the hemorrhagic form in the population. This study aimed to investigate the effect of Piper aduncum, Piper marginatum and Piper nigrum essential oils against Aedes aegypti larvae. In an effort to find a natural effective and affordable way to control this endemic disease, the larvicidal activities of essential oils from the plants were analyzed for activity comparison by measurement of their LC₅₀ . The essential oils isolated by hydrodistillation were analyzed by GC/MS. The main components identified were: β-pinene (32.7%) and E-caryophyllene (17.1%) in P. aduncum; isoelemecin (21.7%) and apiole (20.1%) in P. marginatum and E-caryophyllene (24.2%) and caryophyllene oxide (20.1%) in P. nigrum. The results show that Piper marginatum presented the LC50 of 8.29 μg/mL and these are the first report about the larvicidal activity of P. aduncum. These results suggest that the essential oil of Piper species are promising as larvicide against A. aegypti larvae. http://sedici.unlp.edu.ar:80/handle/10915/7933 Comunicacion Latin American Journal of Pharmacy; vol. 29, no. 3 D-002 is a mixture of 6 high molecular weight primary alcohols purified from beeswax with anti-inflammatory and antioxidant effects. This study investigated the in vitro genotoxic potential of D-002 to produce chromosomal aberrations (CA) in peripheral blood lymphocytes. Fresh suspensions of BWA were added (500; 750, 1000, 2500 and 5000 μg/mL) to cultures with (microsomal liver fraction S9 mix) or without metabolic activation. Concurrent negative (Tween/water vehicle) and positive controls (cyclophosphamide 15 μg/mL and mitomicyn C (0.3 μg/mL in the tests with and without metabolic activation, respectively) were included. Two hundred (200) metaphases by group were examined and the numbers and frequencies of cells with aberrations and the mitotic index were quantified. D-002 added up to 5 mg/mL of culture did not induce chromosomal aberrations in presence or not of S9 mix compared with negative controls and no trends with the doses were observed. Positive controls evidenced increases on the numbers and frequencies of CA. Mitotic indexes were unchanged with the treatment, which indicates that D-002 does not affect cell proliferation. In conclusion, BWA added in vitro (0.5-5 mg/mL) to peripheral blood lymphocyte cultures did not show evidences of cytotoxic or genotoxic potential in the CA test. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7933 2010-01-01T00:00:00Z D-002 is a mixture of 6 high molecular weight primary alcohols purified from beeswax with anti-inflammatory and antioxidant effects. This study investigated the in vitro genotoxic potential of D-002 to produce chromosomal aberrations (CA) in peripheral blood lymphocytes. Fresh suspensions of BWA were added (500; 750, 1000, 2500 and 5000 μg/mL) to cultures with (microsomal liver fraction S9 mix) or without metabolic activation. Concurrent negative (Tween/water vehicle) and positive controls (cyclophosphamide 15 μg/mL and mitomicyn C (0.3 μg/mL in the tests with and without metabolic activation, respectively) were included. Two hundred (200) metaphases by group were examined and the numbers and frequencies of cells with aberrations and the mitotic index were quantified. D-002 added up to 5 mg/mL of culture did not induce chromosomal aberrations in presence or not of S9 mix compared with negative controls and no trends with the doses were observed. Positive controls evidenced increases on the numbers and frequencies of CA. Mitotic indexes were unchanged with the treatment, which indicates that D-002 does not affect cell proliferation. In conclusion, BWA added in vitro (0.5-5 mg/mL) to peripheral blood lymphocyte cultures did not show evidences of cytotoxic or genotoxic potential in the CA test. http://sedici.unlp.edu.ar:80/handle/10915/7932 Comunicacion Latin American Journal of Pharmacy; vol. 29, no. 3 The methanolic extract of the whole plant of Oxalis corniculata was evaluated for antioxidant and membrane stabilizing activities. The total phenolics in the methanol extract was found 213.69 mg of gallic acid per g of extract when determined using the Folin-Ciocalteu reagent. Besides, antioxidant activity was also assessed by various methods, including free radical, hydrogen peroxide, and nitric oxide scavenging and phosphomolybdenum antioxidant assay and reducing power determination. In these cases, butylated hydroxytoluene (BHT) and ascorbic acid were used as a standard antioxidants. The membrane stabilizing activity was assessed by using erythrocyte in hypotonic solution, using indomethacin as the standard. It was revealed that the methanolic extract of O. corniculata demonstrated moderate antioxidant activity and significant membrane stabilizing property. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7932 2010-01-01T00:00:00Z The methanolic extract of the whole plant of Oxalis corniculata was evaluated for antioxidant and membrane stabilizing activities. The total phenolics in the methanol extract was found 213.69 mg of gallic acid per g of extract when determined using the Folin-Ciocalteu reagent. Besides, antioxidant activity was also assessed by various methods, including free radical, hydrogen peroxide, and nitric oxide scavenging and phosphomolybdenum antioxidant assay and reducing power determination. In these cases, butylated hydroxytoluene (BHT) and ascorbic acid were used as a standard antioxidants. The membrane stabilizing activity was assessed by using erythrocyte in hypotonic solution, using indomethacin as the standard. It was revealed that the methanolic extract of O. corniculata demonstrated moderate antioxidant activity and significant membrane stabilizing property. http://sedici.unlp.edu.ar:80/handle/10915/7931 Comunicacion Latin American Journal of Pharmacy; vol. 29, no. 3 Fracionamento cromatográfico da fração em diclorometano obtida do extrato etanólico das cascas do tronco de Scutia buxifolia Reissek (Rhamnaceae) conduziu ao isolamento de lupeol, β-sitosterol e estigmasterol. As estruturas foram identificadas através de técnicas espectroscópicas usuais, além da comparação com dados relatados na literatura. Os compostos isolados são relatados pela primeira vez para a espécie S. buxifolia.; Fractionation of the dichloromethane soluble fraction from the ethanol extract of the stem bark of Scutia buxifolia Reissek (Rhamnaceae) led to the isolation of lupeol, β-sitosterol and stigmasterol. The structures of the isolates were elucidated by spectroscopic analysis and comparison with literature data. The isolated compounds are reported for the first time to the species S. buxifolia. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7931 2010-01-01T00:00:00Z Fracionamento cromatográfico da fração em diclorometano obtida do extrato etanólico das cascas do tronco de Scutia buxifolia Reissek (Rhamnaceae) conduziu ao isolamento de lupeol, β-sitosterol e estigmasterol. As estruturas foram identificadas através de técnicas espectroscópicas usuais, além da comparação com dados relatados na literatura. Os compostos isolados são relatados pela primeira vez para a espécie S. buxifolia. Fractionation of the dichloromethane soluble fraction from the ethanol extract of the stem bark of Scutia buxifolia Reissek (Rhamnaceae) led to the isolation of lupeol, β-sitosterol and stigmasterol. The structures of the isolates were elucidated by spectroscopic analysis and comparison with literature data. The isolated compounds are reported for the first time to the species S. buxifolia. http://sedici.unlp.edu.ar:80/handle/10915/7930 Articulo The process of drug selection and standardization in small and medium size hospitals of the south region of Santa Catarina, Brazil Latin American Journal of Pharmacy; vol. 29, no. 3 Os procedimentos relacionados com o processo de Seleção e Padronização de Medicamentos foram analisados em 25 Farmácias Hospitalares dos Hospitais do sul do estado de Santa Catarina – Brasil. Os dados foram coletados através de questionário estruturado, aplicado in loco na forma de entrevista e posteriormente consolidados pela abordagem metodológica do Discurso do Sujeito Coletivo. Os resultados apontam que nenhum dos hospitais dispõe de Comissão de Farmácia e Terapêutica e em torno de 70% dos hospitais a escolha dos medicamentos é realizada exclusivamente pelos médicos. Em relação à prescrição de medicamentos não padronizados, em 80 % dos casos prevalece o parecer médico e em apenas dois hospitais há uma política pré-estabelecida e consensuada para medicamentos que não façam parte da lista de medicamentos padronizados.; The process of selection and standardization of drugs employed by inpatient in 25 small and medium size hospitals of the south region of Santa Catarina has been analyzed. The data were collected by means of a structured questionnaire, applied in loco as an interview with the responsible for the Hospital Pharmacy service. The thematic discourse analysis technique was employed for data analysis. The results pointed out that none of the hospitals has a committee of pharmaceutics and therapeutics and, in about 70% of the hospitals, the drug selection and standardization is carried out exclusively by the physicians. Concerning to the prescription of the non-standardized drugs, in 80 % of the studied cases, the doctor’s opinion prevailed and, in only 2 hospitals, there was a pre-defined and consensual policy for the inclusion of drugs that in the list of standardized ones. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7930 2010-01-01T00:00:00Z Os procedimentos relacionados com o processo de Seleção e Padronização de Medicamentos foram analisados em 25 Farmácias Hospitalares dos Hospitais do sul do estado de Santa Catarina – Brasil. Os dados foram coletados através de questionário estruturado, aplicado in loco na forma de entrevista e posteriormente consolidados pela abordagem metodológica do Discurso do Sujeito Coletivo. Os resultados apontam que nenhum dos hospitais dispõe de Comissão de Farmácia e Terapêutica e em torno de 70% dos hospitais a escolha dos medicamentos é realizada exclusivamente pelos médicos. Em relação à prescrição de medicamentos não padronizados, em 80 % dos casos prevalece o parecer médico e em apenas dois hospitais há uma política pré-estabelecida e consensuada para medicamentos que não façam parte da lista de medicamentos padronizados. The process of selection and standardization of drugs employed by inpatient in 25 small and medium size hospitals of the south region of Santa Catarina has been analyzed. The data were collected by means of a structured questionnaire, applied in loco as an interview with the responsible for the Hospital Pharmacy service. The thematic discourse analysis technique was employed for data analysis. The results pointed out that none of the hospitals has a committee of pharmaceutics and therapeutics and, in about 70% of the hospitals, the drug selection and standardization is carried out exclusively by the physicians. Concerning to the prescription of the non-standardized drugs, in 80 % of the studied cases, the doctor’s opinion prevailed and, in only 2 hospitals, there was a pre-defined and consensual policy for the inclusion of drugs that in the list of standardized ones. http://sedici.unlp.edu.ar:80/handle/10915/7929 Articulo Thermal Characterization of Gelatin-Chitosan Free Films Crosslinked with Genipin Latin American Journal of Pharmacy; vol. 29, no. 3 Hidrocolóides têm sido amplamente estudados no desenvolvimento de novos materiais voltados a aplicação em sistemas para liberação modificada de fármacos, especialmente em função das características de biodegradabilidade e ampla variedade de estruturas e propriedades. Todavia muitos desses materiais apresentam elevada hidrossolubilidade, podendo quando aplicados na condição de carreadores de fármaco, promover liberação prematura do conteúdo. Esta limitação encontra na reticulação química alternativa promissora tanto em nível terapêutico quanto industrial. Neste trabalho foram estudadas as propriedades térmicas de filmes isolados de gelatina, quitosana e suas associações, reticulados com genipina, através das técnicas de termogravimetria (TG) e calorimetria exploratória diferencial (DSC). Os resultados demonstraram que a reticulação com genipina em todas as composições avaliadas, promoveu maior resistência à perda de massa tanto por evaporação de água, quanto por degradação térmica. Filmes com maior concentração de quitosana apresentaram maior hidrofilicidade, cuja característica foi mantida após a reticulação dos filmes com genipina.; The use of hydrocolloids had been widely studied for development of new materials for modified drug delivery system, due to their characteristics, like biodegradability and availability in a variety of structure with varied properties, although due to their high water solubility can lead to early drug delivery and the chemical modification can be an alternative for this inconvenience. Gelatin-Chitosan free films crosslinked with genipin were studied in terms of thermal properties by thermogravimetry (TG) and differential scanning calorimetry (DSC). The results demonstrated that films crosslinked with genipin in all the evaluated compositions promoted higher resistance to the mass change due to the water evaporation and thermal degradation. Films with higher concentration of chitosan presented higher hydrophilicity and this characteristic was kept even after to promote the crosslink with genipin. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7929 2010-01-01T00:00:00Z Hidrocolóides têm sido amplamente estudados no desenvolvimento de novos materiais voltados a aplicação em sistemas para liberação modificada de fármacos, especialmente em função das características de biodegradabilidade e ampla variedade de estruturas e propriedades. Todavia muitos desses materiais apresentam elevada hidrossolubilidade, podendo quando aplicados na condição de carreadores de fármaco, promover liberação prematura do conteúdo. Esta limitação encontra na reticulação química alternativa promissora tanto em nível terapêutico quanto industrial. Neste trabalho foram estudadas as propriedades térmicas de filmes isolados de gelatina, quitosana e suas associações, reticulados com genipina, através das técnicas de termogravimetria (TG) e calorimetria exploratória diferencial (DSC). Os resultados demonstraram que a reticulação com genipina em todas as composições avaliadas, promoveu maior resistência à perda de massa tanto por evaporação de água, quanto por degradação térmica. Filmes com maior concentração de quitosana apresentaram maior hidrofilicidade, cuja característica foi mantida após a reticulação dos filmes com genipina. The use of hydrocolloids had been widely studied for development of new materials for modified drug delivery system, due to their characteristics, like biodegradability and availability in a variety of structure with varied properties, although due to their high water solubility can lead to early drug delivery and the chemical modification can be an alternative for this inconvenience. Gelatin-Chitosan free films crosslinked with genipin were studied in terms of thermal properties by thermogravimetry (TG) and differential scanning calorimetry (DSC). The results demonstrated that films crosslinked with genipin in all the evaluated compositions promoted higher resistance to the mass change due to the water evaporation and thermal degradation. Films with higher concentration of chitosan presented higher hydrophilicity and this characteristic was kept even after to promote the crosslink with genipin. http://sedici.unlp.edu.ar:80/handle/10915/7928 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases involved in chronic myelogenous leukemia and gastrointestinal stromal tumors. Mice were given imatinib PO (50 mg/kg) or IV (12.5 mg/kg) and plasma, liver, brain, spleen, kidney disposition profiles analyzed. Plasma t1/2 was 4.5 h. IV plasma AUC0→∞ was 11.59 μg·h/mL, MRT was 4.87 h, Cl was 1.08 l/h/kg and VSS was 5.23 l/kg. PO AUC0→∞ was 12.82 μg·h/mL, MRT 5.1 h, CMAX was 6.99 ± 2.84 μg/mL, absorption rate constant, Ka was 4.348 h–1, bioavailability was 27.7%, VSS was 5.51 l/kg. The hepatic extraction ratio was 0.384 and the minimum dose fraction absorbed was 0.450. IV AUC0→∞ tissue-to-plasma ratios were 2.59 (spleen, kidney) and 2.91 (liver) but increased after PO administration in spleen (3.68) and kidney (3.49) and decreased in liver (2.75). Liver and kidney correlations with plasma concentrations suggests perfusion-limited uptake. Spleen counter-clockwise profile suggests non-concentration dependent uptake. Brain penetration was minimal. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7928 2010-01-01T00:00:00Z Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases involved in chronic myelogenous leukemia and gastrointestinal stromal tumors. Mice were given imatinib PO (50 mg/kg) or IV (12.5 mg/kg) and plasma, liver, brain, spleen, kidney disposition profiles analyzed. Plasma t1/2 was 4.5 h. IV plasma AUC0→∞ was 11.59 μg·h/mL, MRT was 4.87 h, Cl was 1.08 l/h/kg and VSS was 5.23 l/kg. PO AUC0→∞ was 12.82 μg·h/mL, MRT 5.1 h, CMAX was 6.99 ± 2.84 μg/mL, absorption rate constant, Ka was 4.348 h–1, bioavailability was 27.7%, VSS was 5.51 l/kg. The hepatic extraction ratio was 0.384 and the minimum dose fraction absorbed was 0.450. IV AUC0→∞ tissue-to-plasma ratios were 2.59 (spleen, kidney) and 2.91 (liver) but increased after PO administration in spleen (3.68) and kidney (3.49) and decreased in liver (2.75). Liver and kidney correlations with plasma concentrations suggests perfusion-limited uptake. Spleen counter-clockwise profile suggests non-concentration dependent uptake. Brain penetration was minimal. http://sedici.unlp.edu.ar:80/handle/10915/7927 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 Morphoanathomical parameters, for macroscopic and microscopic analyses of the cladodes of Nopalea cochenillifera, plant recognized traditionally like medicinal, allow his authenticity. The phylloclades have wavyness and areoles with three straight and hyaline thorns. The uniseriate epidermis has parallelocytic stomata and mucilaginous cells, followed by an annular collenchyma and a palisade parenchyma on average with eight cell layers. The vascular region is constituted by isolated vascular bundles of the open collateral type. The central cylinder is composed by a parenchymatic medulla. The mucilage structures and the druses of calcium oxalate are present in cortical region in and central cylinder. They are in bigger number near to the vascular bundles. The druses also take place in the first layer of the collenchyma. These morphoanathomical characteristics, when taken together, are consistent in the botanical control of quality of this vegetable sort. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7927 2010-01-01T00:00:00Z Morphoanathomical parameters, for macroscopic and microscopic analyses of the cladodes of Nopalea cochenillifera, plant recognized traditionally like medicinal, allow his authenticity. The phylloclades have wavyness and areoles with three straight and hyaline thorns. The uniseriate epidermis has parallelocytic stomata and mucilaginous cells, followed by an annular collenchyma and a palisade parenchyma on average with eight cell layers. The vascular region is constituted by isolated vascular bundles of the open collateral type. The central cylinder is composed by a parenchymatic medulla. The mucilage structures and the druses of calcium oxalate are present in cortical region in and central cylinder. They are in bigger number near to the vascular bundles. The druses also take place in the first layer of the collenchyma. These morphoanathomical characteristics, when taken together, are consistent in the botanical control of quality of this vegetable sort. http://sedici.unlp.edu.ar:80/handle/10915/7926 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 No posee resumen. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7926 2010-01-01T00:00:00Z No posee resumen. http://sedici.unlp.edu.ar:80/handle/10915/7925 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 Diabetes mellitus (DM) is a serious health problem affecting millions of individuals worldwide. It is showed that some changes of many enzymes and transporters concerned with metabolism and disposal of drug have taken place in organism under pathologic state of DM. The pharmacokinetic of drug should be different between diabetic and normal animals. Rutin and quercetin can also be used to treatment of diabetic mellitus. So, this paper investigated the difference of pharmacokinetic profiles of rutin and quercetin in diabetic and normal rats in vivo by HPLC-DAD method. The pharmacokinetic parameters were analyzed by double-compartmental method (DAS2.0). The pharmacokinetic parameters of rutin in normal and diabetic rats were: (22.203 ± 2.6) and (36.174 ± 7.5) mg · h/L for AUC(0-4); (0.726 ± 0.13) and (1.069 ± 0.17) h for MRT(0-4), (5.413 ± 0.57) and (6.595 ± 0.38) h for t1/2; (0.424 ± 0.071) and (0.226 ± 0.072) L/h/kg for Cl, respectively. The pharmacokinetic parameters of quercetin in normal and diabetic rats were: (5.243 ± 0.82) and (2.376 ± 0.61) mg h/L for AUC(0-4); (2.556 ± 0.52) and (1.616 ± 0.35) h for MRT(0-4), (1.216 ± 0.17) and (0.992 ± 0.12) h for t1/2; (1.918 ± 0.32) and (4.342 ± 0.99) L/h/kg for Cl, respectively. Those results indicate that the pharmacokinetic profiles of rutin and quercetin were changed by DM. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7925 2010-01-01T00:00:00Z Diabetes mellitus (DM) is a serious health problem affecting millions of individuals worldwide. It is showed that some changes of many enzymes and transporters concerned with metabolism and disposal of drug have taken place in organism under pathologic state of DM. The pharmacokinetic of drug should be different between diabetic and normal animals. Rutin and quercetin can also be used to treatment of diabetic mellitus. So, this paper investigated the difference of pharmacokinetic profiles of rutin and quercetin in diabetic and normal rats in vivo by HPLC-DAD method. The pharmacokinetic parameters were analyzed by double-compartmental method (DAS2.0). The pharmacokinetic parameters of rutin in normal and diabetic rats were: (22.203 ± 2.6) and (36.174 ± 7.5) mg · h/L for AUC(0-4); (0.726 ± 0.13) and (1.069 ± 0.17) h for MRT(0-4), (5.413 ± 0.57) and (6.595 ± 0.38) h for t1/2; (0.424 ± 0.071) and (0.226 ± 0.072) L/h/kg for Cl, respectively. The pharmacokinetic parameters of quercetin in normal and diabetic rats were: (5.243 ± 0.82) and (2.376 ± 0.61) mg h/L for AUC(0-4); (2.556 ± 0.52) and (1.616 ± 0.35) h for MRT(0-4), (1.216 ± 0.17) and (0.992 ± 0.12) h for t1/2; (1.918 ± 0.32) and (4.342 ± 0.99) L/h/kg for Cl, respectively. Those results indicate that the pharmacokinetic profiles of rutin and quercetin were changed by DM. http://sedici.unlp.edu.ar:80/handle/10915/7924 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 Twelve compounds were isolated from the rhizoma of Paris polyphylla Smith var. pubescens Handel-Mazzetti. Based on spectral data, the isolated compounds were identified as stigmasterol (1), β- Ecdysterone (2), Diosgenin (3), Ophiopogonin C’ (4), Diosgenin-3-O-α-L-arabinofuranosyl(1→4)-β-D-glucoside (5), Dioscin (6), Paris saponin I (7), Paris saponin II (8), Pennogenin-3-O-α-L- arabinofuranosyl (1→4)- β- D-glucoside (9), Paris saponin VI (10), Pennogennin- 3-O-α-L-arabinofuranosyl(1→4)-[α-Lrhamnopyranosyl(1→2)]-β-D-glucoside (11) and Paris saponin VII (12). Their cytotoxicity and anti-migration on mouse B16 melanoma cells were evaluated. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7924 2010-01-01T00:00:00Z Twelve compounds were isolated from the rhizoma of Paris polyphylla Smith var. pubescens Handel-Mazzetti. Based on spectral data, the isolated compounds were identified as stigmasterol (1), β- Ecdysterone (2), Diosgenin (3), Ophiopogonin C’ (4), Diosgenin-3-O-α-L-arabinofuranosyl(1→4)-β-D-glucoside (5), Dioscin (6), Paris saponin I (7), Paris saponin II (8), Pennogenin-3-O-α-L- arabinofuranosyl (1→4)- β- D-glucoside (9), Paris saponin VI (10), Pennogennin- 3-O-α-L-arabinofuranosyl(1→4)-[α-Lrhamnopyranosyl(1→2)]-β-D-glucoside (11) and Paris saponin VII (12). Their cytotoxicity and anti-migration on mouse B16 melanoma cells were evaluated. http://sedici.unlp.edu.ar:80/handle/10915/7923 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 The aim of the present investigation is to improve the dissolution of poorly water soluble drug valsartan by preparing solid dispersions and also to evaluate the effect of different inert carriers on flow properties of solid dispersion. Valsartan is a poorly soluble drug useful in the treatment of hypertension. Absorption window of valsartan is stomach and upper part of small intestine. One possible way to improve dissolution rate is solid dispersions of the drug. The solid dispersions were prepared by solvent evaporation method using HPMC E5 LV as water soluble carrier, as use of HPMC low viscosity polymers for solid dispersion preparations were reported in literature. But film formation took place during solid dispersion formulation and was creating difficulty in releasing the drug from formulation; and those solid dispersions, were not free flowing. Thus such preparations are not useful from the formulation development point of view. So to improve the flow properties some inert material were tried like microcrystalline cellulose (MCC) and lactose. The solid dispersions were evaluated for drug content, solubility and dissolution studies. In vitro drug release of solid dispersions was studied by USP type II paddle dissolution apparatus. For the solid dispersion the solubility and dissolution of the drug increased with the increase in the carrier concentration. Probable mechanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (Powder XRD) and Scanning Electron Microscopy (SEM) of drug, physical mixture and solid dispersions. This study revealed that solid dispersions technique is promising and useful for valsartan to improve its solubility and dissolution and incorporation of inert carriers improved the flow property of solid dispersion. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7923 2010-01-01T00:00:00Z The aim of the present investigation is to improve the dissolution of poorly water soluble drug valsartan by preparing solid dispersions and also to evaluate the effect of different inert carriers on flow properties of solid dispersion. Valsartan is a poorly soluble drug useful in the treatment of hypertension. Absorption window of valsartan is stomach and upper part of small intestine. One possible way to improve dissolution rate is solid dispersions of the drug. The solid dispersions were prepared by solvent evaporation method using HPMC E5 LV as water soluble carrier, as use of HPMC low viscosity polymers for solid dispersion preparations were reported in literature. But film formation took place during solid dispersion formulation and was creating difficulty in releasing the drug from formulation; and those solid dispersions, were not free flowing. Thus such preparations are not useful from the formulation development point of view. So to improve the flow properties some inert material were tried like microcrystalline cellulose (MCC) and lactose. The solid dispersions were evaluated for drug content, solubility and dissolution studies. In vitro drug release of solid dispersions was studied by USP type II paddle dissolution apparatus. For the solid dispersion the solubility and dissolution of the drug increased with the increase in the carrier concentration. Probable mechanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (Powder XRD) and Scanning Electron Microscopy (SEM) of drug, physical mixture and solid dispersions. This study revealed that solid dispersions technique is promising and useful for valsartan to improve its solubility and dissolution and incorporation of inert carriers improved the flow property of solid dispersion. http://sedici.unlp.edu.ar:80/handle/10915/7922 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 The production of biopharmaceuticals by transgenic plants is a promising choice to achieve the multi-kilogram amount of products needed to treat many human diseases. However, this scientific field is still lacking of approved specific guidelines regarding points to consider for manufacturing and application of these products. In such sense, the implementation of new manufacturing processes and quality systems using the quality risks management is recognized as something of prime importance in the current pharmaceutical industry. In this work, we summarize the application of the FMEA method to design the manufacturing process of a plantibody, employed in the hepatitis B vaccine production to ensure the vaccine high quality. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7922 2010-01-01T00:00:00Z The production of biopharmaceuticals by transgenic plants is a promising choice to achieve the multi-kilogram amount of products needed to treat many human diseases. However, this scientific field is still lacking of approved specific guidelines regarding points to consider for manufacturing and application of these products. In such sense, the implementation of new manufacturing processes and quality systems using the quality risks management is recognized as something of prime importance in the current pharmaceutical industry. In this work, we summarize the application of the FMEA method to design the manufacturing process of a plantibody, employed in the hepatitis B vaccine production to ensure the vaccine high quality. http://sedici.unlp.edu.ar:80/handle/10915/7921 Articulo Antioxidant activity of three species of Eugenia (Myrtaceae) Latin American Journal of Pharmacy; vol. 29, no. 3 A atividade antioxidante dos extratos vegetais de Eugenia brasiliensis, E. beaurepaireana e E. umbelliflora foi avaliada usando diferentes métodos: Determinação da ação sequestrante de radicais livres usando DPPH, determinação do potencial redutor e determinação do potencial inibidor da peroxidação lipídica. Foi correlacionado também a o conteúdo de fenólicos totais e de flavonóides contidos nestes extratos e frações com a atividade antioxidante. As espécies E. brasiliensis e E. beaurepaireana mostraram maior capacidade antioxidante em relação a todos os métodos utilizados. Estas espécies exibiram também maior teor de compostos fenólicos. Uma significante relação entre a atividade antioxidante e o conteúdo de fenólicos foi observado, indicando que estes compostos são os principais contribuintes para as propriedades antioxidantes nestas plantas.; Extracts of Eugenia brasiliensis, E. beaurepaireana and E. umbelliflora were investigated for their antioxidant activity using DPPH, reducing potential and B-carotene-linoleate system. Total phenolics and flavonoids contents were also determined. E. brasiliensis and E. beaurepaireana showed the highest antioxidant capacities in all methods used. These species exhibited too the highest phenolic contents. A significant relationship between antioxidant capacity and total phenolic content was found, indicating that phenolic compounds are the major contributors to the antioxidant properties of these plants. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7921 2010-01-01T00:00:00Z A atividade antioxidante dos extratos vegetais de Eugenia brasiliensis, E. beaurepaireana e E. umbelliflora foi avaliada usando diferentes métodos: Determinação da ação sequestrante de radicais livres usando DPPH, determinação do potencial redutor e determinação do potencial inibidor da peroxidação lipídica. Foi correlacionado também a o conteúdo de fenólicos totais e de flavonóides contidos nestes extratos e frações com a atividade antioxidante. As espécies E. brasiliensis e E. beaurepaireana mostraram maior capacidade antioxidante em relação a todos os métodos utilizados. Estas espécies exibiram também maior teor de compostos fenólicos. Uma significante relação entre a atividade antioxidante e o conteúdo de fenólicos foi observado, indicando que estes compostos são os principais contribuintes para as propriedades antioxidantes nestas plantas. Extracts of Eugenia brasiliensis, E. beaurepaireana and E. umbelliflora were investigated for their antioxidant activity using DPPH, reducing potential and B-carotene-linoleate system. Total phenolics and flavonoids contents were also determined. E. brasiliensis and E. beaurepaireana showed the highest antioxidant capacities in all methods used. These species exhibited too the highest phenolic contents. A significant relationship between antioxidant capacity and total phenolic content was found, indicating that phenolic compounds are the major contributors to the antioxidant properties of these plants. http://sedici.unlp.edu.ar:80/handle/10915/7920 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 Paeonol is a micromolecular phenolic compound and it is the main component of Chinese herbal medicine that has been isolated from the root bark of Paeonia moutan. Paeonol is identified to have various physiological activities. In this study the antitumor activity and the possible mechanisms of paeonol were investigated in mice bearing EMT6 breast cancer model. The results showed that paeonol (150 mg/kg and 300 mg/kg) effectively reduced the weight of EMT6 breast tumor. Compared with the control group, paeonol significantly increased the number of tumor cells in G0/G1 phase, increased the number of cells in apoptosis and decreased the number of cells in S phase and G2/M, inhibited the expression of mutant p53, Bcl-2 and C-erbB-2 protein. The mechanisms of paeonol of antitumor effects might be associated with inhibition of tumor cells in G0/G1 phase, inducing cell apoptosis and inhibiting the expression of mutant p53, Bcl-2 and C-erbB-2 protein. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7920 2010-01-01T00:00:00Z Paeonol is a micromolecular phenolic compound and it is the main component of Chinese herbal medicine that has been isolated from the root bark of Paeonia moutan. Paeonol is identified to have various physiological activities. In this study the antitumor activity and the possible mechanisms of paeonol were investigated in mice bearing EMT6 breast cancer model. The results showed that paeonol (150 mg/kg and 300 mg/kg) effectively reduced the weight of EMT6 breast tumor. Compared with the control group, paeonol significantly increased the number of tumor cells in G0/G1 phase, increased the number of cells in apoptosis and decreased the number of cells in S phase and G2/M, inhibited the expression of mutant p53, Bcl-2 and C-erbB-2 protein. The mechanisms of paeonol of antitumor effects might be associated with inhibition of tumor cells in G0/G1 phase, inducing cell apoptosis and inhibiting the expression of mutant p53, Bcl-2 and C-erbB-2 protein. http://sedici.unlp.edu.ar:80/handle/10915/7919 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 Fungi play a predominant role in microbial infections with serious health risk to immunocompromised individuals, including AIDS, cancer, diabetics, newborns and elderly patients. Fungi specific riboflavin metabolism involves lumazine synthase catalyzed synthesis of 6,7-dimethyl-8-D-ribityl lumazine which is converted to riboflavin by a riboflavin synthase. Therefore lumazine synthase has been targeted for design of newer antifungal agents. 32 novel N-substituted aryl amine derivatives have been designed, synthesized, characterized and screened as antifungals. Molecular modelling and docking studies with fungal lumazine synthase using the 32 inhibitors have elucidated unique binding areas within the active site of the enzyme. Amongst the selected 2-D QSAR descriptors, chiV3Cluster and Most +ve Potential show positive correlation with antifungal activity while XX Polarizability, XY Polarizability, Heat of Formation and Quadruple 3 show negative correlation with antifungal activity. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7919 2010-01-01T00:00:00Z Fungi play a predominant role in microbial infections with serious health risk to immunocompromised individuals, including AIDS, cancer, diabetics, newborns and elderly patients. Fungi specific riboflavin metabolism involves lumazine synthase catalyzed synthesis of 6,7-dimethyl-8-D-ribityl lumazine which is converted to riboflavin by a riboflavin synthase. Therefore lumazine synthase has been targeted for design of newer antifungal agents. 32 novel N-substituted aryl amine derivatives have been designed, synthesized, characterized and screened as antifungals. Molecular modelling and docking studies with fungal lumazine synthase using the 32 inhibitors have elucidated unique binding areas within the active site of the enzyme. Amongst the selected 2-D QSAR descriptors, chiV3Cluster and Most +ve Potential show positive correlation with antifungal activity while XX Polarizability, XY Polarizability, Heat of Formation and Quadruple 3 show negative correlation with antifungal activity. http://sedici.unlp.edu.ar:80/handle/10915/7918 Articulo Latin American Journal of Pharmacy; vol. 29, no. 3 The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal drug delivery. The objective of the present investigation was to develop a mucoadhesive in situ gel with reduced nasal mucocilliary clearance in order to improve the bioavailability of the antiemetic drug, metoclopramide hydrochloride. The in situ gelation upon contact with nasal mucosa was conferred via the use of the thermogelling Pluronic flake 127 (18%). Mucoadhesion was modulated via the use of hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (Na CMC) and sodium alginate (Na-alginate) whereas drug release was modified by varying concentrations of polyethylene glycol 6000 (PEG 6000). The results revealed that the different mucoadhesives increased the gel viscosity but reduced its sol gel transition temperatures. The increase in viscosity was highest in formulations with Na-alginate and lowest in formulations with HPMC. PEG 6000 significantly decreased mucoadhesive strength of formula containing 0.3% HPMC (776.6 ± 19.55 to 713.6 ± 5.03), 0.2% Na CMC (656 ± 11.13 to 575 ± 9.07) and 0.2% Na-alginate (659 ± 11.13 to 618.3 ± 9.45) whereas the gelation temperature increased by 3 to 4 °C. 100% of drug diffusion was found at four hours for formulation F5, F9, and F12. Formulation F5 showed maximum permeability (0.00949 ± 0.00021 mg.cm/min) than other formulation containing PEG6000. This study concluded the potential use of mucoadhesive in situ nasal gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved nasal bioavailability. Fri, 01 Jan 2010 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7918 2010-01-01T00:00:00Z The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal drug delivery. The objective of the present investigation was to develop a mucoadhesive in situ gel with reduced nasal mucocilliary clearance in order to improve the bioavailability of the antiemetic drug, metoclopramide hydrochloride. The in situ gelation upon contact with nasal mucosa was conferred via the use of the thermogelling Pluronic flake 127 (18%). Mucoadhesion was modulated via the use of hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (Na CMC) and sodium alginate (Na-alginate) whereas drug release was modified by varying concentrations of polyethylene glycol 6000 (PEG 6000). The results revealed that the different mucoadhesives increased the gel viscosity but reduced its sol gel transition temperatures. The increase in viscosity was highest in formulations with Na-alginate and lowest in formulations with HPMC. PEG 6000 significantly decreased mucoadhesive strength of formula containing 0.3% HPMC (776.6 ± 19.55 to 713.6 ± 5.03), 0.2% Na CMC (656 ± 11.13 to 575 ± 9.07) and 0.2% Na-alginate (659 ± 11.13 to 618.3 ± 9.45) whereas the gelation temperature increased by 3 to 4 °C. 100% of drug diffusion was found at four hours for formulation F5, F9, and F12. Formulation F5 showed maximum permeability (0.00949 ± 0.00021 mg.cm/min) than other formulation containing PEG6000. This study concluded the potential use of mucoadhesive in situ nasal gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved nasal bioavailability.