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1.
Water Res ; 246: 120716, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37837900

RESUMO

Ammoniacal nitrogen (NH4N) is a ubiquitous nitrogen pollutant found in wastewater, which could cause eutrophication and severe environmental stress. It is therefore necessary to manage NH4N by enrichment and recovery for potential reuse, as well as to regulate the amount of environmental discharge. Hybridization of membrane-based processes is an attractive option for further enhancing water and nutrient reclamation from waste streams; thus, in this present work, a hybrid osmotically assisted reverse osmosis (OARO) and reverse osmosis (RO) process was demonstrated for subsequent ammoniacal nitrogen enrichment and wastewater discharge management. Using a commercially-available cellulose triacetate membrane module, model and real wastewater containing approximately 4,000ppm NH4N were effectively dewatered and enriched to a final NH4N content of 40,300ppm. This corresponds to enrichment of around 10 times and approximately 90% pure water recovery. The effective combination of both processes resulted in high efficiency, as well as economical and energy-saving benefits, as shown by the process performance and our preliminary techno-economic analysis. The specific energy consumption of the hybrid process projected to operate at a capacity of 2,000 m3h-1 was determined to be 8.8kWh m-3, or 0.56kWh kg-1 NH4Cl removed/recovered for an initial feed solution containing around 15,300ppm NH4Cl. Hybrid OARO and RO operation was able to achieve satisfactory enrichment by the OARO process and obtaining clean water by the RO process. The hybrid OARO-RO process has shown great potential as a suitable end-stage membrane-based process for wastewater dewatering and NH4N enrichment and recovery toward a circular economy and environmental management, as well as clean water recovery.


Assuntos
Águas Residuárias , Purificação da Água , Nitrogênio , Purificação da Água/métodos , Osmose , Membranas Artificiais , Água , Eliminação de Resíduos Líquidos/métodos
2.
Water Sci Technol ; 81(11): 2381-2390, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32784281

RESUMO

Anaerobic membrane bioreactors (AnMBRs) have many advantages, such as producing methane gas for energy generation and little excess sludge. However, membrane fouling is a serious problem because the foulant, which causes the membrane to foul, may get rejected by the membrane and accumulate in the reactor, resulting in an acceleration of membrane fouling. However, there is no information related to a change in the foulant concentration in an AnMBR. Therefore, we examined the changes in the foulant concentration in the reactor, related to membrane fouling in an AnMBR. For the influent, reactor solution, and effluent, the concentration of each component of the foulant was analyzed by using a liquid chromatography-organic carbon detector (LC-OCD). It was found that fouling in the AnMBR was closely related to the components in the reactor, and the main foulant of the ultrafiltration (UF) membrane was biopolymers (BPs). BP accumulated in the reactor because of a high rejection by the UF membrane. However, once the BP accumulated in the reactor was biodegraded, the concentration of BP decreased with time even under a high organic loading rate of 1.9kg TOC/m3/day.


Assuntos
Reatores Biológicos , Eliminação de Resíduos Líquidos , Anaerobiose , Membranas Artificiais , Metano , Esgotos , Águas Residuárias
3.
Int J Pharm ; 532(1): 118-123, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-28842308

RESUMO

As powder agglomeration during storage causes a decrease in the performance of dry powder inhalers (DPIs), it is important to understand the properties of powder agglomeration in developing DPIs. Generally, powder agglomeration is caused by capillary force and crystalline transformation in conditions of higher humidity. It is, however, difficult to correlate crystalline transformation and powder agglomeration, especially when the crystalline transformation is limited. In this study, we focused on the application of inverse gas chromatography (iGC) to detect powder agglomeration directly. There was a slight change between the powder state and lactose agglomerates using powder X-ray diffraction, and dynamic vapor sorption. On the other hand, a change in pressure drop was found during measurement of lactose using iGC. After measurement by iGC, powdered lactose agglomerated. This finding suggests that a pressure drop is related to powder agglomeration and can be employed to detect the onset of powder agglomeration. Based on these findings, we propose a novel index-the Void Forming Index (VFI)-which is related to the pressure drop with iGC. The VFI is a useful index in the evaluation of powder agglomeration, and will be especially useful during DPI development.


Assuntos
Pós/química , Adesividade , Química Farmacêutica , Cromatografia Gasosa , Inaladores de Pó Seco , Lactose/química , Difração de Pó , Pressão , Difração de Raios X
4.
Nihon Shokakibyo Gakkai Zasshi ; 114(2): 238-247, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28163289

RESUMO

A 77-year-old man underwent endoscopic submucosal dissection (ESD) of a type 0-IIc tumor located in the cardiac part of the stomach. The pathological diagnosis of the tumor was poorly differentiated tubular adenocarcinoma with submucosal invasion depth;therefore, radical gastrectomy was also performed. After 1 year and 10 months, liver metastasis was detected because of which partial liver resection was performed. The pathological diagnosis of the tumor was neuroendocrine carcinoma (NEC). The pathology of the ESD specimen was re-examined, and a diagnosis of gastric NEC was made;furthermore, the liver tumor was regarded as metachronous metastasis. Despite the radical excision of the stage IA tumor, metastasis occurred. Chemotherapy with S-1 alone was successfully performed after the liver resection while considering the advanced age of the patient. Follow-up revealed no signs of recurrence at 1 year and 4 months after the treatment, indicating that the S-1 therapy may be considered for treating NEC in elderly and medically compromised patients owing to its mild side effects.


Assuntos
Adenocarcinoma/secundário , Carcinoma Neuroendócrino/secundário , Neoplasias Hepáticas/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/cirurgia , Quimioterapia Adjuvante , Combinação de Medicamentos , Ressecção Endoscópica de Mucosa , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Masculino , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Fatores de Tempo
5.
Int J Pharm ; 422(1-2): 170-8, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22079715

RESUMO

The objective of this study was to investigate the effect of preparation methods on the surface/bulk molecular mobility and glass fragility of solid dispersions. Solid dispersions containing indomethacin and PVP K30 were chosen as the model system. An inverse gas chromatography method was used to determine the surface structural relaxation of the solid dispersions and these data were compared to those for bulk relaxation obtained by DSC. The values of τ(ß) for the surface relaxation were 4.6, 7.1 and 1.8h for melt quenched, ball milled and spray dried solid dispersions respectively, compared to 15.6, 7.9 and 9.8h of the bulk. In all systems, the surface had higher molecular mobility than the bulk. The glass fragility of the solid dispersions was also influenced by the preparation methods with the most fragile system showing the best stability. The zero mobility temperature (T(0)) was used to correlate with the physical stability of the solid dispersions. Despite having similar T(g) (65°C), the T(0) of the melt quenched, ball milled and spray dried samples were 21.6, -4.2 and 16.7°C respectively which correlated well with their physical stability results. Therefore, T(0) appears to be a better indicator than T(g) for predicting stability of amorphous materials.


Assuntos
Anti-Inflamatórios não Esteroides/química , Indometacina/química , Povidona/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cromatografia Gasosa , Composição de Medicamentos , Estabilidade de Medicamentos , Modelos Químicos , Estrutura Molecular , Propriedades de Superfície , Tecnologia Farmacêutica/métodos , Temperatura , Fatores de Tempo
6.
Chem Pharm Bull (Tokyo) ; 59(12): 1452-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22130365

RESUMO

The surface of amorphous compounds crystallizes faster compared to the bulk. This suggests that molecules at the surface have high molecular mobility. Crystallization behavior is affected by various factors including molecular weight and glass transition temperature (T(g)). In this study, we focus on troglitazone which is composed of diastereomers, RR/SS and RS/SR, as model compound, because each diastereomer has the same molecular weight and similar chemical structure. Troglitazone is isolated into each diastereomer, and both amorphous prepared from RR/SS and RS/SR showed similar T(g) (around 60°C). The surface relaxation of each amorphous troglitazone prepared from two diastereomers, RR/SS and RS/SR, was determined to compare surface molecular mobility, using inverse gas chromatography under dry conditions. As a result, amorphous prepared from RS/SR, showed the shorter surface relaxation time at 40°C (temperature below T(g)), which means it has higher molecular mobility than that from RR/SS at the surface although both have the same molecular weight and similar T(g). Microscopy analysis was conducted to observe the crstallization behavior at the surface of amorphous troglitazone in conditions of high temperature and humidity. Micrographs showed that crystallization area at the surface of amorphous prepared from RS/SR, which showed the shorter surface relaxation time, increased faster than that of the amorphous prepared from RR/SS. Although the reason for the difference in the surface relaxation time of each amorphous troglitazone could not be determined, factors such as the difference of configuration might affect the difference.


Assuntos
Antineoplásicos/química , Cromanos/química , Tiazolidinedionas/química , Cromatografia Gasosa , Cristalização , Estereoisomerismo , Propriedades de Superfície , Temperatura de Transição , Troglitazona
7.
Hepatol Res ; 40(4): 337-45, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20070402

RESUMO

AIM: Hepatic stellate cell (HSC) proliferation plays a pivotal role in liver fibrogenesis, and agents that suppress HSC activation, including platelet-derived growth factor (PDGF)-induced HSC proliferation, are good candidates for antifibrogenic therapies. In this report, we use the LI90 HSC line to elucidate the antifibrogenic effects of proanthocyanidin derived from the leaves of Vaccinium virgatum. METHODS: Proanthocyanidin (PAC) was extracted from the leaves of blueberry V. virgatum (BB-PAC), grape seeds (GS-PAC) and Croton lechleri (CL-PAC). These extracts were examined for their effects on PDGF-BB-induced LI90 cell proliferation and DNA synthesis. Extracellular signal-regulated kinase (ERK) and Akt phosphorylation and PDGF receptor-beta (PDGFR-beta) expression were evaluated by western blot analysis. RESULTS: BB-PAC potently suppressed PDGF-BB-induced proliferation and DNA synthesis of LI90 cells. BB-PAC also suppressed PDGF-BB-induced DNA synthesis in primary cultured rat HSC. Moreover, GS-PAC and CL-PAC suppressed PDGF-BB-induced DNA synthesis in LI90 cells. In contrast, the monomeric PAC catechin and epicatechin and dimeric PAC procyanidin B2 only slightly suppressed PDGF-BB-induced DNA synthesis. Western blot analysis showed that BB-PAC completely or partially inhibited PDGF-BB-induced ERK and Akt phosphorylation, respectively. In addition, BB-PAC partially inhibited the PDGF-BB-induced degradation of PDGFR-beta. CONCLUSION: Our results suggest that BB-PAC suppresses activated HSC by inhibiting the PDGF signaling pathway. In addition, these results provide novel findings that may facilitate the development of antifibrogenic agents.

8.
Oncol Lett ; 1(5): 905-911, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22966404

RESUMO

The present study aimed to retrospectively compare the survival rates between patients treated with transcatheter arterial chemoembolization and hepatic resection for solitary hepatocellular carcinoma (HCC). According to our database, derived from three affiliated hospitals, the inclusion criteria for this study were: solitary HCC [Child-Pugh class A and International Union Against Cancer (UICC) stage T1-3N0M0] treated between July 1990 and October 2001. Subsequently, hepatic resection (149 patients) as well as chemoembolization (102 patients) groups were selected. Following stratification according to tumor stage [UICC, Cancer of the Liver Italian Program (CLIP) and Milan criteria], survival rates were compared between the treatment groups. Survival rates were calculated using the Kaplan-Meier method. Age, gender and size of the HCC did not differ significantly between the groups. Moreover, no significant difference in the survival rates (average hepatic resection, 58.9 months; average chemoembolization, 45 months; P=0.1697) was observed between the groups. In the subgroup analysis, according to tumor stage, the survival rate was significantly higher for the hepatic resection group than for the chemoembolization group in the UICC T3N0M0 (P=0.017) subgroup. However, no significant differences in survival rates were observed between the hepatic resection and chemoembolization groups for UICC T1 (P=0.7329), T2N0M0 (P=0.5741), CLIP0 (P=0.3593), CLIP1-2 (P=0.3287) and within (>5 cm; P=0.4429) and beyond Milan criteria (≤5 cm; P=0.4003) subgroups. Chemoembolization is as effective as hepatic resection in treating solitary HCC in subpopulations with UICC T1-2N0M0 or CLIP 0-2 HCC or Milan criteria and adequate liver function. In the subgroup with UICC T3N0M0 HCC, hepatic resection is superior to chemoembolization.

9.
Hepatology ; 50(2): 393-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19585614

RESUMO

UNLABELLED: The overall mortality of patients infected with hepatitis C virus (HCV) has not been fully elucidated. This study analyzed mortality in subjects positive for antibody to HCV (anti-HCV) in a community-based, prospective cohort study conducted in an HCV hyperendemic area of Japan. During a 10-year period beginning in 1995, 1125 anti-HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005. Cause of death was assessed by death certificates. Subjects with detectable HCV core antigen (HCVcAg) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers; subjects who were negative for both HCVcAg and HCV RNA (i.e., viremia-negative) were considered as having had a prior HCV infection and were classified as HCV noncarriers. Among the anti-HCV-positive subjects included in the analysis, 758 (67.4%) were HCV carriers, and 367 were noncarriers. A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years: 176 deaths in the HCV carrier group and 55 in the noncarrier group. The overall mortality rate was higher in HCV carriers than in noncarriers, adjusted for age and sex (hazard ratio, 1.53; 95% confidence interval, 1.13-2.07). Although liver-related deaths occurred more frequently among the HCV carriers (hazard ratio, 5.94; 95% confidence interval, 2.58-13.7), the rates of other causes of death did not differ between HCV carriers and noncarriers. Among HCV carriers, a higher level of HCVcAg (>or=100 pg/mL) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality. CONCLUSION: The presence of viremia increases the rate of mortality, primarily due to liver-related death, among anti-HCV-seropositive persons in Japan.


Assuntos
Hepatite C Crônica/mortalidade , Viremia/mortalidade , Idoso , Portador Sadio/epidemiologia , Feminino , Seguimentos , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
J Hepatobiliary Pancreat Surg ; 16(3): 359-66, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19300896

RESUMO

BACKGROUND/PURPOSE: It has been reported that hepatic resection may be preferable to other modalities for the treatment of small hepatocellular carcinomas (HCCs), by contributing to improved overall and disease-free survival. Ablation techniques such as radiofrequency ablation (RFA) have also been used as therapy for small HCCs; however, few studies have compared the two treatments based on long-term outcomes. The effectiveness of hepatic resection and RFA for small nodular HCCs within the Milan criteria were compared. METHODS: A retrospective cohort study was performed with 278 consecutive patients who underwent curative hepatic resection (n = 123) or initial RFA percutaneously (n = 110) or surgically (thoracoscopic-, laparoscopic-, and open-approaches; n = 45) for HCC. The selection criteria for treatment were based on uniform criteria. Mortality related to therapy and 3- and 5-year overall and disease-free survivals were analyzed. RESULTS: The model for endstage liver disease (MELD) scores for all patients in the series were less than 13. There were no therapy-related mortalities in either the hepatic resection or RFA groups. The incidence of death within 1 year after therapy (1.6 and 1.9%, respectively) was similar in the hepatic resection and RFA groups. The group that underwent hepatic resection showed a trend towards better survival (P = 0.06) and showed significantly better disease-free survival (P = 0.02) compared with the RFA group, although differences in liver functional reserve existed. The advantage of hepatic resection was more evident for patients with single tumors and patients with grade A liver damage. In contrast, patients with multinodular tumors survived longer when treated with RFA, regardless of the grade of liver damage. Further analysis showed that surgical RFA could potentially have survival benefits similar to those of hepatic resection for single tumors, and that surgical RFA had the highest efficacy for treating multinodular tumors. CONCLUSIONS: In patients with small HCCs within the Milan criteria, hepatic resection should still be employed for those patients with a single tumor and well-preserved liver function. RFA should be chosen for patients with an unresectable single tumor or those with multinodular tumors, regardless of the grade of liver damage. In order to increase long-term oncological control, surgical RFA seems preferable to percutaneous RFA, if the patient's condition allows them to tolerate surgery.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Ablação por Cateter/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Laparotomia/métodos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Seleção de Pacientes , Guias de Prática Clínica como Assunto/normas , Probabilidade , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento
11.
J Pharm Sci ; 98(6): 2133-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18837010

RESUMO

Amorphous dispersions provide an excellent way of increasing dissolution rates of poorly soluble drugs, but there may be concerns about stability. One way of assessing the stability of amorphous is the study of relaxation. In this study the relaxation at the surface of amorphous solid dispersions (SDs) was evaluated using inverse gas chromatography (IGC). A SD containing 70% indometacin and 30% PVP K30 was prepared by melt-quenching. The SD was put into the IGC and heated to 17 degrees C below T(g) for aging, during which time decane was injected repeatedly. The retention volume of decane decreased with aging time, indicating that the sample relaxed at the surface. During this storage no crystallization was observed by PXRD and DSC. Therefore, it is obvious that the change in this retention volume is due to the structural relaxation of the amorphous SD. The data of retention volume showed a good fit on a Kohlraush-Williams-Watts (KWW) equation and the indicator of the relaxation, tau(beta), was estimated. It was much lower than that of bulk relaxation estimated by DSC. Therefore, it can be concluded that the structural relaxation at the surface happens faster than that of the bulk. The potential significance of these findings is discussed.


Assuntos
Cromatografia Gasosa/métodos , Indometacina/química , Polivinil/química , Pirrolidinas/química , Alcanos/química , Varredura Diferencial de Calorimetria , Cristalização , Composição de Medicamentos , Estabilidade de Medicamentos , Cinética , Estrutura Molecular , Solubilidade , Propriedades de Superfície , Temperatura , Difração de Raios X
12.
Int J Pharm ; 361(1-2): 12-8, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18584979

RESUMO

Troglitazone containing two asymmetric carbons has four isomers. Crystalline troglitazone consists of two crystalline diastereomer-pairs, RR/SS and RS/SR, which have different melting points. Using a closed melting method, troglitazone-polyvinylpyrrolidone solid dispersions with various crystallinities were prepared. Raman spectroscopy and its mapping technique were applied to discriminate between the crystalline RR/SS, crystalline RS/SR and amorphous form of troglitazone in solid dispersions. The results of the Raman mapping of solid dispersions showed the co-existence of crystal and amorphous forms, and which diastereomer-pairs remained as crystals, in addition to the distribution of the drug. Moreover, the distribution of PVP could be illustrated from the Raman mapping data. Thus, Raman spectroscopy and its mapping technique are useful tools to evaluate crystal and amorphous states, including discrimination of crystalline diastereomer-pairs in solid dispersions. In addition, by describing the distribution of the drug and the carrier, it could be guessed how drug crystals become amorphous during preparation from the point of view of the distribution of the amorphous form of the drug substance and the carrier.


Assuntos
Cromanos/análise , Análise Espectral Raman/métodos , Tiazolidinedionas/análise , Química Farmacêutica , Cromanos/química , Cristalização , Formas de Dosagem , Portadores de Fármacos/química , Estereoisomerismo , Tiazolidinedionas/química , Temperatura de Transição , Troglitazona
13.
J Gastroenterol ; 42(8): 673-80, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17701131

RESUMO

BACKGROUND: The clinical features of hepatitis C virus (HCV) carriers with persistently normal alanine aminotransferase (PNALT) levels (ALT < or = 34 IU/l) have not been fully elucidated. We investigated clinical factors associated with ALT flare-up in PNALT individuals in a HCV hyperendemic area of Japan. METHODS: We analyzed 101 HCV carriers who had PNALT between 1993 and 2000. The first occurrence of ALT flare-up (ALT > or = 35 IU/l) between 2001 and 2005 was evaluated by the Kaplan-Meier method. Multivariate analysis of factors predicting ALT flare-up were conducted using Cox proportional hazards models. RESULTS: The mean follow-up period was 2.8 years, and the 5-year cumulative incidence of ALT flare-up was estimated to be 31.8%. In multivariate analysis, an ALT level of 20-34 IU/l and a high serum ferritin level (> or =90 ng/ml) in the most recently available data up to the year 2000, as well as H63D heterozygosity in the HFE gene, were independently and strongly associated with the incidence of ALT flare-up (Hazard ratios = 5.6, 3.1, and 4.8, respectively). In addition, HFE H63D heterozygosity was significantly associated with higher serum ferritin levels in subjects with PNALT (153.8 + or - 73.3 ng/ml in subjects with the 63HD genotype vs. 89.4 + or - 51.3 ng/ml in subjects with the 63HH genotype, P = 0.043). CONCLUSIONS: HCV carriers with PNALT in this population were at risk for ALT flare-up. Basal ALT levels, serum ferritin levels, and HFE polymorphism are potentially important predictors of ALT flare-up.


Assuntos
Alanina Transaminase/sangue , Doenças Endêmicas/estatística & dados numéricos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/enzimologia , Hepatite C Crônica/epidemiologia , Idoso , Biomarcadores/sangue , DNA/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Proteína da Hemocromatose , Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/imunologia , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Incidência , Japão/epidemiologia , Masculino , Proteínas de Membrana/genética , Mutação , Prognóstico , Estudos Prospectivos , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Int J Pharm ; 338(1-2): 79-86, 2007 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-17321085

RESUMO

The effects of the process parameters of high shear wet granulation on the granule properties and dissolution properties of mefenamic acid from tablets have been studied, and the importance of evaluating the consolidation of granules has been considered. The process parameters selected for investigation were the amount of water added, the impeller rotation speed and the kneading time. Increases in the amount of water and the kneading time led to increases in the particle diameter of the granules and to decreases in the mean pore diameter. The mean pore diameter decreased with increases in the impeller rotation speed, while the particle diameters were independent of the impeller rotation speed. The process parameters affected the surface morphology and the internal morphology of the granules. The mean particle diameter and the mean pore diameter of the granules basically correlated with the dissolution properties of the tablets. The contribution of the mean pore diameter to this correlation was higher than that of mean particle diameter. Therefore, it was concluded that evaluation of the granule consolidated state, such as the mean pore diameter, was important in order to assure the dissolution properties of drug products.


Assuntos
Comprimidos , Tecnologia Farmacêutica , Ácido Mefenâmico/química , Tamanho da Partícula , Pós , Solubilidade
15.
Int J Pharm ; 336(1): 82-9, 2007 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-17178201

RESUMO

This study examined the effect of physical properties of troglitazone drug substance on the molecular interaction with polyvinylpyrrolidone K30 (PVP) during preparation by a closed melting method. Milling was conducted using impact and jet mills to change the physical properties of troglitazone, such as particle size, specific surface area, surface free energy and acidic-basic parameters. Solid dispersions (SDs) prepared from milled troglitazone, irrespective of milling method, showed almost 100% dissolution when not less than 7.5% of water was added during heating. SDs prepared from unmilled troglitazone showed almost 100% dissolution when not less than 12.8% of water was added during heating. Physical mixture (PM) containing unmilled troglitazone must be heated above at least 50 degrees C higher than the glass transition temperature (T(g)) of PVP to obtain an SD showing 100% dissolution, while PMs containing milled troglitazone could be heated above only 20 degrees C higher than the T(g) of PVP to obtain an SD showing 100% dissolution. The melting points of troglitazone in PMs containing milled troglitazone, irrespective of milling method, were lower than those in PMs containing unmilled troglitazone. These results indicated that specific interaction could occur more easily during heating between milled troglitazone and PVP during preparation by a closed melting method. In addition, Fourier transform infrared study indicated that hydrogen bonding could occur between the N-H of troglitazone and the C=O of PVP.


Assuntos
Cromanos/química , Excipientes/química , Temperatura Alta , Povidona/química , Tiazolidinedionas/química , Varredura Diferencial de Calorimetria , Cromanos/farmacocinética , Cromatografia Gasosa , Cristalografia , Ligação de Hidrogênio , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Transição de Fase , Inibidores da Agregação Plaquetária/farmacocinética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Termodinâmica , Tiazolidinedionas/farmacocinética , Aderências Teciduais , Temperatura de Transição , Troglitazona , Água/química , Difração de Raios X
16.
Int J Pharm ; 302(1-2): 103-12, 2005 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-16102926

RESUMO

Troglitazone, which possesses two asymmetric carbons, is obtained as a mixture of four isomers present in equal amounts. Troglitazone (Lot T003) has two melting points, about 120 and 175 degrees C. To increase the bioavailability of insoluble troglitazone, troglitazone-polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) were prepared with water by a unique closed melting method. In this study, the effects of the water content in the physical mixture (PM) and the heating temperature on the apparent crystallinity of troglitazone in SDs prepared by this method were investigated. When the water content in the PM was controlled at 3%, although the apparent crystallinity of troglitazone in the SD prepared by heating at 105 degrees C did not decrease (99%), that of the SDs prepared by heating at 130 and 150 degrees C were reduced to 54 and 11%, respectively. This result indicated that the meltage of troglitazone varies depending on the heating temperature. The apparent crystallinity of troglitazone in the SDs decreased with increase in water content in the PM. In particular, SDs prepared by heating at 130 and 150 degrees C showed 0% apparent crystallinity when the water content in the PM were more than 13 and 8%, respectively. When the heating temperature used was higher than the glass transition temperature of PVP plasticized with water, troglitazone crystals were dissolved in the rubbery PVP. Therefore, even if the heating temperature is lower than the melting point of troglitazone during preparation, controlling the water content in the PM at a high level can produce a troglitazone SD with 0% apparent crystallinity.


Assuntos
Cromanos/farmacocinética , Povidona/química , Tiazolidinedionas/farmacocinética , Temperatura de Transição , Água/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Cromanos/química , Cristalização , Concentração de Íons de Hidrogênio , Transição de Fase , Solubilidade , Tiazolidinedionas/química , Troglitazona , Difração de Raios X/métodos
17.
Int J Pharm ; 280(1-2): 39-46, 2004 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-15265545

RESUMO

Solid dispersions of troglitazone with PVP K30 in a weight ratio of 1:2 were prepared by the closed melting method. Solid dispersions that exhibit different degrees of crystallinity (0 and 36%) were prepared by changing the charged amount of water, which functions as a plasticizer for PVP K30. Electron probe microanalysis (EPMA) and microthermal analysis (micro TA) of the solid dispersions were performed to investigate the uniformity and physical state of troglitazone in the solid dispersions. The EPMA study confirmed that troglitazone was dispersed homogeneously in the sample whose apparent crystallinity was 0%. However, the sample with a 36% crystallinity was heterogeneous. The micro TA study showed that the sample with a 36% crystallinity was present in two states, crystal and amorphous. EPMA and micro TA would be useful tools to confirm the uniformity and physical states, respectively, of solid dispersions.


Assuntos
Cromanos/análise , Cromanos/química , Microanálise por Sonda Eletrônica/métodos , Tiazolidinedionas/análise , Tiazolidinedionas/química , Química Farmacêutica , Análise Diferencial Térmica/métodos , Troglitazona
18.
Anticancer Res ; 23(5b): 4191-6, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14666624

RESUMO

To clarify the cumulative recurrence-free interval and survival rate with hepatitis C virus (HCV)-related single, small hepatocellular carcinoma (HCC), we studied 32 patients with surgical resection, 61 with ablation therapy and 28 with transcatheter chemoembolization (TACE). A log-rank test revealed that there were no significant differences in the recurrence-free interval (p = 0.08) and survival (p = 0.279) between the resection and the ablation groups. Univariate analysis using the Cox proportional hazards regression model showed initial treatment (p = 0.0051) was associated with recurrence-free interval. Platelet count (p = 0.009), indocianine green retention rate at 15 minutes (p = 0.003), Child-Pugh classification (p = 0.001), serum albumin level (p = 0.0012) and serum total bililubin (p = 0.015) were associated with survival. Hence patients with HCV-related single, small HCC should be treated according to their hepatic reserve.


Assuntos
Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Hepacivirus , Hepatite C/complicações , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Quimioembolização Terapêutica , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Hepatol Res ; 25(3): 306-311, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12697252

RESUMO

Gallium-67 (67Ga) has been used as tumor or inflammation-imaging agent in nuclear medicine for decades. Although many hypotheses concerning the mechanism of uptake of 67Ga into tumors and inflammation have been proposed, consensus has not been reached. If the mechanism of 67Ga uptake is clarified, we can improve the sensitivity of diagnostic imaging with 67Ga. We attempted to clarify the mechanism of 67Ga uptake by the liver of carbon tetrachloride (CCl(4))-treated rats. First, we investigated whether or not transferrin (Tf) is involved in 67Ga uptake by the liver tissue of CCl(4)-treated rats. It is well known that Fe(3+) can inhibit the binding of 67Ga to Tf. The administration of FeCl(3) 5 min before the injection of 67Ga slightly enhanced the uptake of 67Ga by the liver tissue of CCl(4)-treated rats. The entering of 67Ga into hepatocytes of CCl(4)-treated rats was similar to the uptake by the liver tissue. In addition, the administration of FeCl(3) slightly increased the entering of 67Ga to hepatocytes. These results suggest that free 67Ga enters into hepatocytes from the liver of CCl(4)-treated rats.

20.
Int J Pharm ; 250(1): 283-6, 2003 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-12480293

RESUMO

States of interaction between indomethacin (IM) and polyvinylpyrrolidone (PVP) in an amorphous solid dispersion prepared by co-grinding were compared with those between IM and silica nanoparticles. Changes in the carbon chemical states of the solid dispersions were evaluated based on the chemical shift in the 13C-CP/MAS-NMR. Hydrogen bonds between the amide carbonyl of PVP particles and the carboxyl groups of IM molecules were formed by co-grinding. Despite the wide difference in carrier properties, the apparent equilibrium solubility (AES) of IM in the ground IM-PVP mixture was predicted by solid state NMR on the basis of the relationship previously established for IM with SiO(2). This indicates that AES is affected solely by the state of IM, irrespective of the carrier species, and despite carrier-dependent chemical interactions.


Assuntos
Indometacina/administração & dosagem , Povidona/administração & dosagem , Dióxido de Silício/administração & dosagem , Portadores de Fármacos , Indometacina/química , Espectroscopia de Ressonância Magnética
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