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[PMID]:28697427
[Au] Autor:Hajirezaee S; Mirvaghefi A; Farahmand H; Agh N
[Ad] Dirección:Department of Fisheries, Faculty of Natural Resources, University of Tehran, Karaj, Iran.
[Ti] Título:NMR-based metabolomic study on the toxicological effects of pesticide, diazinon on adaptation to sea water by endangered Persian sturgeon, Acipenser persicus fingerlings.
[So] Fuente:Chemosphere;185:213-226, 2017 Oct.
[Is] ISSN:1879-1298
[Cp] País de publicación:England
[La] Idioma:eng
[Ab] Resumen:NMR-based metabolomics was applied to explore metabolic impacts of diazinon on sea water adaptation of Persian sturgeon fingerlings, Acipenser persicus. Fingerlings were exposed to sub-lethal concentrations of diazinon in freshwater (FW) for 96 h (short-term trial) and 12 days (long-term trial) and then exposed in brackish water (BW) (12 mg L salinity) for 24 h. After 96 h and 12 days exposure in FW, identified metabolites (amino acids, osmolytes, energy metabolites) showed different change-patterns compared to control group (P < 0.05) as follow: (A) short-term trial: higher plasma levels of glucose, lactate (in all diazinon-exposed fish), acetate and acetoacetate (in 0.9 mg L diazinon treatment); lower levels of creatine (in all diazinon-exposed fish), trimethylamine-N-oxide, choline, taurine, betaine, N,N-dimethylglycine and almost all amino acids in fish exposed to high concentrations of diazinon (0.54 and 0.9 mg L diazinon). (B) Long-term trial: higher plasma levels of lipid oxidation metabolites and almost all amino acids in fish exposed to 0.54 and 0.9 mg L diazinon; lower levels of creatine, trimethylamine-N-oxide, N,N-dimethylglycine, betaine, choline (in all diazinon-exposed fish), glucose (in 0.54 and 0.9 mg L diazinon treatments) and taurine (in 0.9 mg L diazinon treatment). When fish were exposed in BW for 24 h, the plasma levels of osmolytes decreased significantly in almost all experimental groups of short-term and long-term trial (P < 0.05). In short-term trial, the plasma levels of glucose in all groups and lactate in 0.18 and 0.54 mg L diazinon treatments increased after salinity challenge (P < 0.05). However, a significant decrease was observed in lactate levels in 0.9 mg L diazinon treatment (P < 0.05). Also, the plasma levels of amino acids decreased mostly in fish of control group than exposed fish (P < 0.05). The plasma glycerol concentration showed a significant decrease only in fish of 0.54 mg L diazinon treatment (P < 0.05). In long term trial, the energetic metabolites (acetate, acetoacetate, glycerol) showed significant increases mostly in fish exposed to high concentrations of diazinon (P < 0.05). Phosphocreatine was detected only in groups exposed to 0.54 and 0.9 mg L diazinon. Some amino acids decreased in control and diazinon-exposed groups while glycine (in control and 0.18 mg L diazinon treatment), glutamine and alanine (in 0.9 mg L diazinon treatment) elevated significantly after 24 h acclimation in BW (P < 0.05). Our results may help to understand the effects of pesticides on fish osmoregulation from a metabolic approach.
[Mh] Términos MeSH primario: Adaptación Fisiológica/efectos de drogas
Cinarizina/metabolismo
Diazinón/toxicidad
Especies en Peligro de Extinción
Metabolómica/métodos
[Mh] Términos MeSH secundario: Animales
Peces/metabolismo
Peces/fisiología
Espectroscopía de Resonancia Magnética/métodos
Osmorregulación/efectos de drogas
Plaguicidas/toxicidad
Salinidad
Agua de Mar
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Pesticides); 3DI2E1X18L (Cinnarizine); YUS1M1Q929 (Diazinon)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170711
[St] Status:MEDLINE


  2 / 728 MEDLINE  
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[PMID]:28472575
[Au] Autor:Tachere RO; Modirrousta M
[Ti] Título:Beyond anxiety and agitation: A clinical approach to akathisia.
[So] Fuente:Aust Fam Physician;46(5):296-298, 2017.
[Is] ISSN:0300-8495
[Cp] País de publicación:Australia
[La] Idioma:eng
[Ab] Resumen:BACKGROUND: When patients suddenly become restless and are unable to sit or stand still, especially in general medical settings, anxiety is often the topmost differential on every clinician's mind. However, the possibility of the very subjectively distressing condition called 'akathisia' should always be considered. OBJECTIVE: The aim of this article is to discuss a clinical approach to the management of akathisia, drawing on the presentation of a patient who was admitted to a general medical ward. DISCUSSION: Akathisia, a subjective and very distressing feeling of restlessness, has been found to be caused by a wide range of medications used in general medical settings, such as azithromycin, antiemetics and antipsychotics. Despite its high incidence and association with an increase in suicidal thoughts, it often goes unrecognised. This paper highlights the need for its early recognition, provides a diagnostic guide and an approach to its management.
[Mh] Términos MeSH primario: Ansiedad/etiología
Agitación Psicomotora/complicaciones
Agitación Psicomotora/diagnóstico
[Mh] Términos MeSH secundario: Adulto
Antidepresivos/efectos adversos
Antidepresivos/uso terapéutico
Antieméticos/efectos adversos
Antieméticos/uso terapéutico
Antipsicóticos/efectos adversos
Antipsicóticos/uso terapéutico
Ansiedad/diagnóstico
Buspirona/efectos adversos
Buspirona/uso terapéutico
Cinarizina/efectos adversos
Cinarizina/uso terapéutico
Diltiazem/efectos adversos
Diltiazem/uso terapéutico
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico
Femenino
Humanos
Metildopa/efectos adversos
Metildopa/uso terapéutico
Agitación Psicomotora/etiología
Reserpina/efectos adversos
Reserpina/uso terapéutico
Ideación Suicida
[Pt] Tipo de publicación:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Antidepressive Agents); 0 (Antiemetics); 0 (Antipsychotic Agents); 3DI2E1X18L (Cinnarizine); 56LH93261Y (Methyldopa); 8B1QWR724A (Reserpine); EE92BBP03H (Diltiazem); TK65WKS8HL (Buspirone)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171102
[Lr] Fecha última revisión:171102
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170504
[St] Status:MEDLINE


  3 / 728 MEDLINE  
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[PMID]:27986997
[Au] Autor:Lin HL; Lin HC; Tseng YF; Chen SC; Hsu CY
[Ad] Dirección:Department of Neurology, Sijhih Cathay General Hospital, No. 2, Ln. 59, Jiancheng Rd., Sijhih Dist, New Taipei City, 221, Taiwan.
[Ti] Título:Risk of parkinsonism induced by flunarizine or cinnarizine: a population-based study.
[So] Fuente:Eur J Clin Pharmacol;73(3):365-371, 2017 Mar.
[Is] ISSN:1432-1041
[Cp] País de publicación:Germany
[La] Idioma:eng
[Ab] Resumen:PURPOSE: This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls. METHODS: Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997-1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded. RESULTS: The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758-6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not. CONCLUSIONS: This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine.
[Mh] Términos MeSH primario: Cinarizina/efectos adversos
Flunarizina/efectos adversos
Trastornos Parkinsonianos/etiología
[Mh] Términos MeSH secundario: Adulto
Anciano
Anciano de 80 o más Años
Estudios de Casos y Controles
Femenino
Humanos
Masculino
Mediana Edad
Estudios Retrospectivos
Factores de Riesgo
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
3DI2E1X18L (Cinnarizine); R7PLA2DM0J (Flunarizine)
[Em] Mes de ingreso:1704
[Cu] Fecha actualización por clase:170920
[Lr] Fecha última revisión:170920
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:161217
[St] Status:MEDLINE
[do] DOI:10.1007/s00228-016-2181-3


  4 / 728 MEDLINE  
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[PMID]:27793717
[Au] Autor:Yasmin R; Rao S; Bremmell K; Prestidge C
[Ad] Dirección:School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
[Ti] Título:Synergistic role of solid lipid and porous silica in improving the oral delivery of weakly basic poorly water soluble drugs.
[So] Fuente:Eur J Pharm Sci;96:508-514, 2017 Jan 01.
[Is] ISSN:1879-0720
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:Oral absorption of weakly basic drugs (e.g. cinnarizine (CIN)) is limited by their pH dependent precipitation in intestinal conditions. To overcome this challenge, a novel drug delivery system composed of solid lipid and porous silica, namely silica encapsulated solid lipid (SESL) particles, was developed via hot homogenization of melted lipid dispersion, followed by ultra-sonication of the silica stabilized homogenized melted lipid dispersion. Scanning electron microscope (SEM) images of the SESL formulation revealed non-spherical and aggregated hybrid particles, with rough exterior and structured nanoparticles visible on the surface. A 1.5, 2.2 and 7-fold improvement in the dissolution of CIN was observed for the SESL particles, under simulated intestinal non-digesting conditions, in comparison to the drug loaded in solid lipid (CIN-SL) matrix, drug loaded in porous silica (CIN-PS) and pure drug powder. Under simulated intestinal digestive condition, significant improvement in the drug solubilization was reported for the SESL formulation in compared to the individual drug loaded systems i.e. CIN-PS and CIN-SL. Thereby, silica encapsulated solid lipid system provides a promising oral delivery approach for poorly water soluble weakly basic drugs.
[Mh] Términos MeSH primario: Cinarizina/química
Portadores de Fármacos/química
Sistemas de Liberación de Medicamentos/métodos
Lípidos/química
Dióxido de Silicio/química
[Mh] Términos MeSH secundario: Administración Oral
Cinarizina/administración & dosificación
Cinarizina/farmacocinética
Portadores de Fármacos/administración & dosificación
Portadores de Fármacos/farmacocinética
Sinergismo Farmacológico
Concentración de Iones de Hidrógeno
Lípidos/administración & dosificación
Lípidos/farmacocinética
Porosidad
Dióxido de Silicio/administración & dosificación
Dióxido de Silicio/farmacocinética
Solubilidad
Agua/metabolismo
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Drug Carriers); 0 (Lipids); 059QF0KO0R (Water); 3DI2E1X18L (Cinnarizine); 7631-86-9 (Silicon Dioxide)
[Em] Mes de ingreso:1704
[Cu] Fecha actualización por clase:170904
[Lr] Fecha última revisión:170904
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:161029
[St] Status:MEDLINE


  5 / 728 MEDLINE  
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[PMID]:27773836
[Au] Autor:Tanaka Y; Kawakami A; Nanimatsu A; Horio M; Matsuoka J; Wada T; Kasaoka S; Yoshikawa H
[Ad] Dirección:Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112, Japan. Electronic address: y-tanaka@ps.hirokoku-u.ac.jp.
[Ti] Título:In vivo evaluation of supersaturation/precipitation/re-dissolution behavior of cinnarizine, a lipophilic weak base, in the gastrointestinal tract: the key process of oral absorption.
[So] Fuente:Eur J Pharm Sci;96:464-471, 2017 Jan 01.
[Is] ISSN:1879-0720
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:The aim of this study is to evaluate how supersaturation, precipitation, and re-dissolution processes influence the intestinal absorption of cinnarizine (CNZ), a lipophilic weak base, by monitoring its plasma and luminal concentration-time profile, after oral administration as a HCl solution containing fluorescein isothiocyanate dextran (FD-4), a non-absorbable marker. In the in vitro pH shift experiment, the supersaturation stability was significantly lower when the higher-concentration solution of CNZ (pH1.5) was added to the simulated intestinal fluid. However, although the in vivo bioavailability after oral administration of high and low dose as HCl solutions was greatly improved compared to those as neutral suspensions, the difference in the supersaturation stability was not reflected in the improvement of the in vivo bioavailability. Analysis of CNZ and FD-4 concentrations in each segment of the gastrointestinal tract revealed that most of the CNZ precipitated in the duodenum after gastric emptying, and supersaturation was observed only in the duodenum. Thereafter, the precipitate was rapidly re-dissolved and absorbed in the upper and middle small intestine. The rapid re-dissolution may be caused by smaller particles of the precipitate. In this case, it is considered that the key process for the absorption of CNZ was re-dissolution, not supersaturation. Therefore, different supersaturation stabilities in different doses observed in in vitro precipitation experiment was not reflected to in vivo absorption. These findings may be useful to design efficient supersaturable formulations and to validate and improve current prediction methods.
[Mh] Términos MeSH primario: Precipitación Química
Cinarizina/administración & dosificación
Cinarizina/metabolismo
Tracto Gastrointestinal/metabolismo
Absorción Intestinal/fisiología
[Mh] Términos MeSH secundario: Administración Oral
Animales
Disponibilidad Biológica
Cinarizina/química
Evaluación Preclínica de Medicamentos/métodos
Tracto Gastrointestinal/efectos de drogas
Absorción Intestinal/efectos de drogas
Masculino
Ratas
Ratas Wistar
Solubilidad/efectos de drogas
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
3DI2E1X18L (Cinnarizine)
[Em] Mes de ingreso:1704
[Cu] Fecha actualización por clase:170904
[Lr] Fecha última revisión:170904
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:161024
[St] Status:MEDLINE


  6 / 728 MEDLINE  
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[PMID]:28189622
[Au] Autor:Dereymaker A; Cinghia G; Van den Mooter G
[Ad] Dirección:Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium.
[Ti] Título:Eudragit® RL as a stabilizer for supersaturation and a substrate for nanocrystal formation.
[So] Fuente:Eur J Pharm Biopharm;114:250-262, 2017 May.
[Is] ISSN:1873-3441
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:In order to optimize supersaturation levels and avoid early drug precipitation, Eudragit® RL was tested as a carrier in solid dispersions, either alone or in combination with a hydrophilic polymer (PVP K25). In vitro dissolution performance of the spray dried solid dispersions was tested. The phase behavior of the produced solid dispersions was analyzed as well as dissolution precipitates. In case of weak acid model compounds (indomethacin and naproxen), the incorporation of Eudragit® RL resulted in a prolongation of supersaturation. A combination of PVP and Eudragit® RL led to high and stable drug concentrations. Eudragit® RL was only suited as a carrier in combination with higher drug loadings. Phase behavior analysis of the produced solid dispersions showed that Eudragit® RL could form glass solutions, and precipitate analysis showed that these drug-polymer combinations remained amorphous after in vitro dissolution for 24h. Surprisingly, indomethacin and naproxen also formed nanocrystals in presence of Eudragit® RL. These nanocrystals were formed by a dynamic interplay of dissolution, sorption and desorption. A charge interaction between anionic drugs and a cationic polymer provided a high driving force for sorption, which was necessary for nanocrystal formation and supersaturation stabilization.
[Mh] Términos MeSH primario: Nanopartículas/química
Polímeros/química
[Mh] Términos MeSH secundario: Cinarizina/química
Desecación
Portadores de Fármacos
Composición de Medicamentos
Indometacina/administración & dosificación
Indometacina/química
Naproxeno/administración & dosificación
Naproxeno/química
Solubilidad
Difracción de Rayos X
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Drug Carriers); 0 (Polymers); 3DI2E1X18L (Cinnarizine); 51822-44-7 (Eudragit RL); 57Y76R9ATQ (Naproxen); XXE1CET956 (Indomethacin)
[Em] Mes de ingreso:1708
[Cu] Fecha actualización por clase:170815
[Lr] Fecha última revisión:170815
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170212
[St] Status:MEDLINE


  7 / 728 MEDLINE  
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[PMID]:27590126
[Au] Autor:Zhang P; Zardán Gómez de la Torre T; Welch K; Bergström C; Strømme M
[Ad] Dirección:Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-751 21, Sweden.
[Ti] Título:Supersaturation of poorly soluble drugs induced by mesoporous magnesium carbonate.
[So] Fuente:Eur J Pharm Sci;93:468-74, 2016 Oct 10.
[Is] ISSN:1879-0720
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:This work investigates whether the solubility of poorly soluble compounds can be improved by using mesoporous magnesium carbonate (MMC) as the drug delivery system. A solvent evaporation method was used to load structurally diverse model drugs (celecoxib, cinnarizine and griseofulvin) into the pores of MMC. The drug-loaded carrier system was then characterized in terms of porosity, crystallinity, and release profiles by a variety of experimental techniques, including X-ray diffraction, nitrogen adsorption analysis, differential scanning calorimetry, infrared spectroscopy, UV absorption spectroscopy, and thermogravimetric analysis. All three drugs were in a non-crystalline state after loading into the pores of MMC. The concentrations of the drugs in solution over time (a measure of the release rates from loaded MMC) were higher than the corresponding concentrations (dissolution rates) of equal amounts of the crystalline drugs. The release rates were five (celecoxib), three (cinnarizine) and two times (griseofulvin) higher than the dissolution rates of their crystalline counterparts. Supersaturation release profiles were also observed; the areas under the concentration-time curves (0-240min) were 25- (celecoxib), 5- (cinnarizine) and 2-fold (griseofulvin) greater than those of the crystalline drugs. Hence, MMC shows promise as a general drug delivery vehicle for increasing the bioavailability of compounds with dissolution rate- or solubility-limited absorption.
[Mh] Términos MeSH primario: Celecoxib/química
Cinarizina/química
Portadores de Fármacos/química
Griseofulvina/química
Magnesio/química
[Mh] Términos MeSH secundario: Algoritmos
Rastreo Diferencial de Calorimetría
Celecoxib/farmacocinética
Cinarizina/farmacocinética
Portadores de Fármacos/farmacocinética
Liberación de Fármacos
Griseofulvina/farmacocinética
Porosidad
Solubilidad
Difracción de Rayos X
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Drug Carriers); 0E53J927NA (magnesium carbonate); 32HRV3E3D5 (Griseofulvin); 3DI2E1X18L (Cinnarizine); I38ZP9992A (Magnesium); JCX84Q7J1L (Celecoxib)
[Em] Mes de ingreso:1704
[Cu] Fecha actualización por clase:170417
[Lr] Fecha última revisión:170417
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:160923
[St] Status:MEDLINE


  8 / 728 MEDLINE  
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[PMID]:27108783
[Au] Autor:Baghel S; Cathcart H; Redington W; O'Reilly NJ
[Ad] Dirección:Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC), Waterford Institute of Technology, Cork Road, Waterford, Ireland. Electronic address: 20065131@mail.wit.ie.
[Ti] Título:An investigation into the crystallization tendency/kinetics of amorphous active pharmaceutical ingredients: A case study with dipyridamole and cinnarizine.
[So] Fuente:Eur J Pharm Biopharm;104:59-71, 2016 Jul.
[Is] ISSN:1873-3441
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form drive them towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) have been selected as model compounds. Thermodynamic fragility (mT) was measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (mD) was evaluated using methods based on extrapolation of configurational entropy to zero [Formula: see text] , and heating rate dependence of Tg [Formula: see text] . The mean relaxation time of amorphous drugs was calculated from the Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of the model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant 'n' which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems were also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. The crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics are found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations.
[Mh] Términos MeSH primario: Cinarizina/química
Dipiridamol/química
Preparaciones Farmacéuticas
[Mh] Términos MeSH secundario: Cromatografía Líquida de Alta Presión
Cristalización
Cinética
Difracción de Polvo
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Pharmaceutical Preparations); 3DI2E1X18L (Cinnarizine); 64ALC7F90C (Dipyridamole)
[Em] Mes de ingreso:1703
[Cu] Fecha actualización por clase:170310
[Lr] Fecha última revisión:170310
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:160609
[St] Status:MEDLINE


  9 / 728 MEDLINE  
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[PMID]:27040196
[Au] Autor:Mishra B; Sahoo J; Dixit PK
[Ad] Dirección:Gayatri College of Pharmacy, Sambalpur, Odisha 768200, India. Electronic address: drbibaswanmishra@gmail.com.
[Ti] Título:Enhanced bioavailability of cinnarizine nanosuspensions by particle size engineering: Optimization and physicochemical investigations.
[So] Fuente:Mater Sci Eng C Mater Biol Appl;63:62-9, 2016 Jun.
[Is] ISSN:1873-0191
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:Cinnarizine (CIN), a poorly soluble drug with erratic bioavailability due to pH dependent solubility has limited advantage to formulate oral solid dosage forms in subject having low gastric acidity. In present study precipitation-ultrasonication was used to fabricate nanosuspensions of cinnarizine stabilized by Poly vinyl alcohol (PVA) to enhance the bioavailability. We investigated the effects of PVA concentration (X1) and solvent to antisolvent ratio (X2) on the quality attributes like mean particle size (Y1); % drug content (Y2); and time required to 90% drug release (Y3) via 3(2) factorial design. The morphology of nanosuspensions was found almost spherical by SEM observation. DSC and FT-IR studies revealed lack of significant interactions between CIN and PVA. Nanosuspensions of mean particle size 621.08 nm was achieved. The dissolution rate obtained from all formulations were markedly higher than pure CIN. Response surface methodology and optimized polynomial equations were used to select the optimal formulation i.e. 0.2% W/V of X1 and 1:42 of X2 to get the desired response Y1; 636.78 nm, Y2; 95.24% and Y3; 7.09 min that were in reasonable agreement with the observed value. The in-vivo study in rat demonstrated that Cmax and AUC0→12 values of nanosuspension were approximately 2.8-fold and 2.7-fold greater than that of reference preparation respectively.
[Mh] Términos MeSH primario: Cinarizina/química
Nanoestructuras/química
[Mh] Términos MeSH secundario: Administración Oral
Animales
Disponibilidad Biológica
Rastreo Diferencial de Calorimetría
Cromatografía Líquida de Alta Presión
Cinarizina/sangre
Cinarizina/farmacocinética
Composición de Medicamentos
Estabilidad de Medicamentos
Vida Media
Masculino
Microscopía Electrónica de Rastreo
Tamaño de la Partícula
Alcohol Polivinílico/química
Ratas
Ratas Wistar
Sonicación
Espectrometría de Fluorescencia
Espectroscopía Infrarroja Transformadora de Fourier
Suspensiones
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Suspensions); 3DI2E1X18L (Cinnarizine); 9002-89-5 (Polyvinyl Alcohol)
[Em] Mes de ingreso:1612
[Cu] Fecha actualización por clase:161230
[Lr] Fecha última revisión:161230
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:160404
[St] Status:MEDLINE


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[PMID]:26969263
[Au] Autor:Olesen NE; Westh P; Holm R
[Ad] Dirección:Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark; NSM, Research Unit for Functional Biomaterials, Roskilde University, Universitetsvej 1, DK-4000 Roskilde, Denmark.
[Ti] Título:A heuristic model to quantify the impact of excess cyclodextrin on oral drug absorption from aqueous solution.
[So] Fuente:Eur J Pharm Biopharm;102:142-51, 2016 May.
[Is] ISSN:1873-3441
[Cp] País de publicación:Netherlands
[La] Idioma:eng
[Ab] Resumen:The intestinal drug solubilising capacity (Dtot(SC)) of a drug formulated as an aqueous cyclodextrin solution is a recently proposed quantity to predict the cyclodextrin concentration needed to fully solubilise the drug in the intestinal lumen. According to this concept, the cyclodextrin concentration in the drug product must be higher than the amount needed to solubilise the compound, due to the displacement of the drug from the cyclodextrin cavity by bile salts in the intestinal lumen. On the other hand, dosing cyclodextrin at >Dtot(SC) is expected to result in decreased free intestinal drug concentrations and thus potentially a lower fraction absorbed. In this study, data from three previous in vivo studies in rats with fixed concentrations of three compounds (danazol, cinnarizine and benzo[A]pyrene) and various cyclodextrin concentrations >Dtot(SC) were analysed. The model was developed for danazol and applied to the two other compounds. Absorption, as quantified from the area under the plasma concentration-time profile, was predicted by the model to decrease at elevated concentrations of co-administered cyclodextrin in accordance with the in vivo data. In addition, at high cyclodextrin concentrations a delay in Tmax and a decrease in Cmax were predicted, again in accordance with the experimental observations. These observations were rationalised in terms of the free intestinal drug concentration by a chemical equilibrium model for Dtot(SC). This model depends on the quantity termed the dimensionless dose concentration, Dtot(∗)=Do/Pn, given as the fraction of the permeation number (Pn) and dose number (Do). The model provides the formulation scientist with a critical quality attribute for assessing the implication of having excess cyclodextrin in an oral solution.
[Mh] Términos MeSH primario: Ciclodextrinas/química
Soluciones/química
Agua/química
[Mh] Términos MeSH secundario: Administración Oral
Animales
Química Farmacéutica/métodos
Cinarizina/química
Danazol/química
Heurística
Absorción Intestinal
Ratas
Solubilidad
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Cyclodextrins); 0 (Solutions); 059QF0KO0R (Water); 3DI2E1X18L (Cinnarizine); N29QWW3BUO (Danazol)
[Em] Mes de ingreso:1612
[Cu] Fecha actualización por clase:161217
[Lr] Fecha última revisión:161217
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:160403
[St] Status:MEDLINE



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