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Piera Di Martino - One of the best experts on this subject based on the ideXlab platform.
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changes in the solid state of Nicergoline a poorly soluble drug under different grinding and environmental conditions effect on polymorphism and dissolution
Journal of Pharmaceutical Sciences, 2019Co-Authors: Roberta Censi, Maria Rosa Gigliobianco, Cristina Casadidio, Piera Di MartinoAbstract:Abstract Nicergoline native crystals (Form I) were subjected to different grinding methods for 15, 30, 45, and 60 min: Method A, grinding at 20°C under air atmosphere; Method B, grinding in presence of liquid nitrogen under air atmosphere; Method C, grinding at 20°C under nitrogen atmosphere; and Method D, grinding in presence of liquid nitrogen under nitrogen atmosphere. Scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry, thermogravimetry, and infrared spectroscopy were used to follow changes in the particle size and in crystalline structures. Batches from Methods A and C underwent partial amorphization immediately after grinding; Form II was obtained by heating these partially amorphous forms or after spontaneous crystallization after 1 and 5 months storage. Method B promoted the hydration of Nicergoline to a monohydrate form. Batch D was stable under grinding and neither amorphization nor hydration were observed. The best intrinsic dissolution rate was that of metastable Form II, followed by Form I, while the worst was that of the Method B monohydrate form. The slowest particle dissolution was observed for hydrated particles, because of the lowest IDR, while the most rapid was exhibited by batch D, because of the very small particle size.
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effect of four different size reduction methods on the particle size solubility enhancement and physical stability of Nicergoline nanocrystals
Drug Development and Industrial Pharmacy, 2014Co-Authors: Valentina Martena, Piera Di Martino, Ranjita Shegokar, Rainer H MullerAbstract:AbstractNicergoline, a poorly soluble active pharmaceutical ingredient, possesses vaso-active properties which causes peripheral and central vasodilatation. In this study, nanocrystals of Nicergoline were prepared in an aqueous solution of polysorbate 80 (nanosuspension) by using four different laboratory scale size reduction techniques: high pressure homogenization (HPH), bead milling (BM) and combination techniques (high pressure homogenization followed by bead milling HPH + BM, and bead milling followed by high pressure homogenization BM + HPH). Nanocrystals were investigated regarding to their mean particles size, zeta potential and particle dissolution. A short term physical stability study on nanocrystals stored at three different temperatures (4, 20 and 40 °C) was performed to evaluate the tendency to change in particle size, aggregation and zeta potential. The size reduction technique and the process parameters like milling time, number of homogenization cycles and pressure greatly affected the si...
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Preformulation study of Nicergoline solid dispersions
2014Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD) in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for one year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer
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Preformulation study of Nicergoline solid dispersions
Journal of Thermal Analysis and Calorimetry, 2013Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by differential scanning calorimetry and X-ray powder diffraction in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for 1 year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer.
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a new nanospray drying method for the preparation of Nicergoline pure nanoparticles
Journal of Nanoparticle Research, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Three different batches of pure nanoparticles (NPs) of Nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Buchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.
Valentina Martena - One of the best experts on this subject based on the ideXlab platform.
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effect of four different size reduction methods on the particle size solubility enhancement and physical stability of Nicergoline nanocrystals
Drug Development and Industrial Pharmacy, 2014Co-Authors: Valentina Martena, Piera Di Martino, Ranjita Shegokar, Rainer H MullerAbstract:AbstractNicergoline, a poorly soluble active pharmaceutical ingredient, possesses vaso-active properties which causes peripheral and central vasodilatation. In this study, nanocrystals of Nicergoline were prepared in an aqueous solution of polysorbate 80 (nanosuspension) by using four different laboratory scale size reduction techniques: high pressure homogenization (HPH), bead milling (BM) and combination techniques (high pressure homogenization followed by bead milling HPH + BM, and bead milling followed by high pressure homogenization BM + HPH). Nanocrystals were investigated regarding to their mean particles size, zeta potential and particle dissolution. A short term physical stability study on nanocrystals stored at three different temperatures (4, 20 and 40 °C) was performed to evaluate the tendency to change in particle size, aggregation and zeta potential. The size reduction technique and the process parameters like milling time, number of homogenization cycles and pressure greatly affected the si...
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Preformulation study of Nicergoline solid dispersions
2014Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD) in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for one year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer
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Preformulation study of Nicergoline solid dispersions
Journal of Thermal Analysis and Calorimetry, 2013Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by differential scanning calorimetry and X-ray powder diffraction in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for 1 year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer.
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a new nanospray drying method for the preparation of Nicergoline pure nanoparticles
Journal of Nanoparticle Research, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Three different batches of pure nanoparticles (NPs) of Nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Buchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.
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Physicochemical characterization of Nicergoline and cabergoline in its amorphous state
Journal of Thermal Analysis and Calorimetry, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Formulation of poorly water-soluble crystalline drugs into their more soluble amorphous form is a common approach for improving their bioavailability. In this study, the amorphous forms of Nicergoline (NIC) and cabergoline (CAB) were obtained by different methods (melting and precipitation under solvent evaporation). The physicochemical characteristics of the samples were determined by HPLC, differential scanning calorimetry (DSC), thermogravimetry, and X-ray powder diffractometry. The physical stability of the amorphous forms was investigated by DSC by considering how the onset temperature and the enthalpy content at the glass transition vary with aging time and temperature. Using the Kohlrausch–Williams–Watts equation on the data obtained from the experiments, the “mean molecular relaxation time constant” ( τ ) was estimated. This parameter was used to understand the stability of NIC and CAB in their glassy state at different temperatures, and results showed that their stability is adequate to enable the formulation of these drugs into solid dosage forms.
Roberta Censi - One of the best experts on this subject based on the ideXlab platform.
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changes in the solid state of Nicergoline a poorly soluble drug under different grinding and environmental conditions effect on polymorphism and dissolution
Journal of Pharmaceutical Sciences, 2019Co-Authors: Roberta Censi, Maria Rosa Gigliobianco, Cristina Casadidio, Piera Di MartinoAbstract:Abstract Nicergoline native crystals (Form I) were subjected to different grinding methods for 15, 30, 45, and 60 min: Method A, grinding at 20°C under air atmosphere; Method B, grinding in presence of liquid nitrogen under air atmosphere; Method C, grinding at 20°C under nitrogen atmosphere; and Method D, grinding in presence of liquid nitrogen under nitrogen atmosphere. Scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry, thermogravimetry, and infrared spectroscopy were used to follow changes in the particle size and in crystalline structures. Batches from Methods A and C underwent partial amorphization immediately after grinding; Form II was obtained by heating these partially amorphous forms or after spontaneous crystallization after 1 and 5 months storage. Method B promoted the hydration of Nicergoline to a monohydrate form. Batch D was stable under grinding and neither amorphization nor hydration were observed. The best intrinsic dissolution rate was that of metastable Form II, followed by Form I, while the worst was that of the Method B monohydrate form. The slowest particle dissolution was observed for hydrated particles, because of the lowest IDR, while the most rapid was exhibited by batch D, because of the very small particle size.
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Preformulation study of Nicergoline solid dispersions
2014Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD) in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for one year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer
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Preformulation study of Nicergoline solid dispersions
Journal of Thermal Analysis and Calorimetry, 2013Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by differential scanning calorimetry and X-ray powder diffraction in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for 1 year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer.
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a new nanospray drying method for the preparation of Nicergoline pure nanoparticles
Journal of Nanoparticle Research, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Three different batches of pure nanoparticles (NPs) of Nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Buchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.
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Physicochemical characterization of Nicergoline and cabergoline in its amorphous state
Journal of Thermal Analysis and Calorimetry, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Formulation of poorly water-soluble crystalline drugs into their more soluble amorphous form is a common approach for improving their bioavailability. In this study, the amorphous forms of Nicergoline (NIC) and cabergoline (CAB) were obtained by different methods (melting and precipitation under solvent evaporation). The physicochemical characteristics of the samples were determined by HPLC, differential scanning calorimetry (DSC), thermogravimetry, and X-ray powder diffractometry. The physical stability of the amorphous forms was investigated by DSC by considering how the onset temperature and the enthalpy content at the glass transition vary with aging time and temperature. Using the Kohlrausch–Williams–Watts equation on the data obtained from the experiments, the “mean molecular relaxation time constant” ( τ ) was estimated. This parameter was used to understand the stability of NIC and CAB in their glassy state at different temperatures, and results showed that their stability is adequate to enable the formulation of these drugs into solid dosage forms.
Angelo Battaglia - One of the best experts on this subject based on the ideXlab platform.
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Nicergoline a drug used for age dependent cognitive impairment protects cultured neurons against β amyloid toxicity
Brain Research, 2005Co-Authors: Filippo Caraci, Angelo Battaglia, Mariangela Chisari, Giuseppina Frasca, Pier Luigi Canonico, Marco Calafiore, Giuseppe Battaglia, Paolo Bosco, Ferdinando Nicoletti, Agata CopaniAbstract:Nicergoline, a drug used for the treatment of Alzheimer's disease and other types of dementia, was tested for its ability to protect neurons against beta-amyloid toxicity. Pure cultures of rat cortical neurons were challenged with a toxic fragment of beta-amyloid peptide (betaAP(25-35)) and toxicity was assessed after 24 h. Micromolar concentrations of Nicergoline or its metabolite, MDL, attenuated betaAP(25-35)-induced neuronal death, whereas MMDL (another metabolite of Nicergoline), the alpha1-adrenergic receptor antagonist, prazosin, or the serotonin 5HT-2 receptor antagonist, methysergide, were inactive. Nicergoline increased the basal levels of Bcl-2 and reduced the increase in Bax levels induced by beta-amyloid, indicating that the drug inhibits the execution of an apoptotic program in cortical neurons. In mixed cultures of rat cortical cells containing both neurons and astrocytes, Nicergoline and MDL were more efficacious than in pure neuronal cultures in reducing beta-amyloid neurotoxicity. Experiments carried out in pure cultures of astrocytes showed that a component of neuroprotection was mediated by a mechanism of glial-neuronal interaction. The conditioned medium of cultured astrocytes treated with Nicergoline or MDL for 72-96 h (collected 24 h after drug withdrawal) was neuroprotective when transferred to pure neuronal cultures challenged with beta-amyloid. In cultured astrocytes, Nicergoline increased the intracellular levels of transforming-growth factor-beta and glial-derived neurotrophic factor, two trophic factors that are known to protect neurons against beta-amyloid toxicity. These results raise the possibility that Nicergoline reduces neurodegeneration in the Alzheimer's brain.
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Nicergoline reverts haloperidol induced loss of detoxifying enzyme activity
European Journal of Pharmacology, 2004Co-Authors: Mariapia Vairetti, Angelo Battaglia, Pier Luigi Canonico, F Berte, Andrea Ferrigno, P RichelmiAbstract:We evaluated the effects of Nicergoline on antioxidant defense enzymes (detoxifying enzymes), during chronic treatment with haloperidol in rats. Chronic use of haloperidol (10 weeks, 1.5 mg/kg/day) induces a significant decrease in glutathione reductase, glutathione peroxidase and superoxide dismutase activity, in selected areas of the brain. Co-administration of Nicergoline (20 days, 10 mg/kg/day) significantly restored the activity of these enzymes to levels comparable to those observed in control rats. These observations suggest beneficial effects of Nicergoline in the prevention and in the treatment of haloperidol-induced side effects.
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1 13c glucose entry in neuronal and astrocytic intermediary metabolism of aged rats a study of the effects of Nicergoline treatment by 13c nmr spectroscopy
Brain Research, 2003Co-Authors: Alfredo Miccheli, Angelo Battaglia, Caterina Puccetti, Giorgio Capuani, Maria Enrica Di Cocco, Luciana Giardino, Laura Calza, Leontino Battistin, Filippo ContiAbstract:Age-related changes in glucose utilization through the TCA cycle were studied using [1-13C]glucose and 13C, 1H NMR spectroscopy on rat brain extracts. Significant increases in lactate levels, as well as in creatine/phosphocreatine ratios (Cr/PCr), and a decrease in N-acetyl-aspartate (NAA) and aspartate levels were observed in aged rat brains as compared to adult animals following glucose administration. The total amount of 13C from [1-13C]glucose incorporated in glutamate, glutamine, aspartate and GABA was significantly decreased in control aged rat brains as compared to adult brains. The results showed a decrease in oxidative glucose utilization of control aged rat brains. The long-term Nicergoline treatment increased NAA and glutamate levels, and decreased the lactate levels as well as the Cr/PCr ratios in aged rat brains as compared to adult rats. The total amount of 13C incorporated in glutamate, glutamine, aspartate, NAA and GABA was increased by Nicergoline treatment, showing an improvement in oxidative glucose metabolism in aged brains. A significant increase in pyruvate carboxylase/pyruvate dehydrogenase activity (PC/PDH) in the synthesis of glutamate in Nicergoline-treated aged rats is consistent with an increase in the transport of glutamine from glia to neurons for conversion into glutamate. In adult rat brains, no effect of Nicergoline on glutamate PC/PDH activity was observed, although an increase in PC/PDH activity in glutamine was, suggesting that Nicergoline affects the glutamate/glutamine cycle between neurons and glia in different ways depending on the age of animals. These results provide new insights into the effects of Nicergoline on the CNS.
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Nicergoline in balance alterations in adult and elderly patients a double blind placebo controlled study
Clinical Drug Investigation, 2002Co-Authors: G Felisati, Angelo Battaglia, Bianca M Rossini, Maria Grazia Papini, O PignataroAbstract:To evaluate the efficacy and safety of Nicergoline in the treatment of balance disorders of central origin in adult and elderly patients. Prospective, double-blind, placebo-controlled, parallel-group, randomised trial of Nicergoline 30mg twice daily and placebo administered for 3 months. After baseline evaluation, patients were assessed monthly for efficacy and safety. The study was carried out in outpatients in five centres in Italy. Eighty-nine adult and elderly outpatients (mean age 67.1 years) with balance disorders of central origin. At baseline, a complete clinical and instrumental otoneurological examination was carried out and the Vertigo-Dizziness Differential Diagnosis Score was calculated. Efficacy was assessed by the Dizziness Assessment Rating Scale (DARS), Dizziness Handicap Inventory (DHI) and static posturography. The safety evaluation included monitoring of adverse events, vital signs, haematology and blood chemistry. The DARS total score was significantly reduced by both treatments; however, score change from baseline was significantly greater in the Nicergoline group compared with the placebo group from the first month of treatment (p = 0.002). The between-treatment difference further increased (p < 0.001) in the following 2 months of treatment up to the end of the study. The DHI score change from baseline was also significantly greater in the Nicergoline group compared with placebo (p < 0.001) at all timepoints, both for the total score and for all domains (functional, emotional and physical). A strong correlation was observed between DARS and DHI total score change from baseline. Static posturography measurements indicated an improvement for almost all considered variables in the Nicergoline group, although no statistically significant difference was observed compared with placebo; however, significant changes from baseline were observed only in the Nicergoline group. Adverse events were observed in 4.5% of the Nicergoline and 4.4% of the placebo patients. Nicergoline is an effective and well tolerated treatment for the clinical symptoms related to central vertigo and improves the quality of life of patients with dizziness.
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antioxidant properties of mdl and mmdl two Nicergoline metabolites during chronic administration of haloperidol
European Journal of Pharmacology, 2002Co-Authors: Mariapia Vairetti, Nicola Carfagna, Angelo Battaglia, Pier Luigi Canonico, F Berte, P RichelmiAbstract:We evaluated the effects of 10-alpha-methoxy-9,10-dihydrolysergol (MDL) and 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), two Nicergoline metabolites, during chronic treatment with haloperidol in rats. Haloperidol induced a significant decrease in the glutathione (GSH) content in selected areas of the brain and in the liver. Prolonged administration of MDL, MMDL or Nicergoline antagonized the haloperidol-induced GSH decrease. Lipid peroxidation in the cortex and striatum was suppressed by MDL, MMDL or Nicergoline administration. Our results show that MDL, MMDL and Nicergoline have antioxidant activity, preventing not only GSH depletion but also lipid peroxidation. These observations suggest beneficial properties of MDL and MMDL in the treatment of neuroleptic-induced side effects.
Ledjan Malaj - One of the best experts on this subject based on the ideXlab platform.
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Preformulation study of Nicergoline solid dispersions
2014Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD) in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for one year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer
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Preformulation study of Nicergoline solid dispersions
Journal of Thermal Analysis and Calorimetry, 2013Co-Authors: Roberta Censi, Valentina Martena, Ela Hoti, Ledjan Malaj, Piera Di MartinoAbstract:Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by differential scanning calorimetry and X-ray powder diffraction in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving Nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for 1 year. The dissolution studies revealed a very high dissolution rate of Nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of Nicergoline in the polymer that enhances the rate of drug release from the polymer.
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a new nanospray drying method for the preparation of Nicergoline pure nanoparticles
Journal of Nanoparticle Research, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Three different batches of pure nanoparticles (NPs) of Nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Buchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.
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Physicochemical characterization of Nicergoline and cabergoline in its amorphous state
Journal of Thermal Analysis and Calorimetry, 2012Co-Authors: Valentina Martena, Ela Hoti, Roberta Censi, Ledjan Malaj, Piera Di MartinoAbstract:Formulation of poorly water-soluble crystalline drugs into their more soluble amorphous form is a common approach for improving their bioavailability. In this study, the amorphous forms of Nicergoline (NIC) and cabergoline (CAB) were obtained by different methods (melting and precipitation under solvent evaporation). The physicochemical characteristics of the samples were determined by HPLC, differential scanning calorimetry (DSC), thermogravimetry, and X-ray powder diffractometry. The physical stability of the amorphous forms was investigated by DSC by considering how the onset temperature and the enthalpy content at the glass transition vary with aging time and temperature. Using the Kohlrausch–Williams–Watts equation on the data obtained from the experiments, the “mean molecular relaxation time constant” ( τ ) was estimated. This parameter was used to understand the stability of NIC and CAB in their glassy state at different temperatures, and results showed that their stability is adequate to enable the formulation of these drugs into solid dosage forms.
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Characterization of Nicergoline polymorphs crystallized in several organic solvents.
2011Co-Authors: Ledjan Malaj, Roberta Censi, D. Capsoni, L. Pellegrino, M. Bini, S. Ferrari, R. Gobetto, V. Massarotti, P. Di MartinoAbstract:Nicergoline (NIC), a poorly water-soluble semisynthetic ergot derivative, was crystallized from several organic solvents, obtaining two different polymorphic forms, the triclinic form I and the orthorhombic form II. NIC samples were then characterized by several techniques such as (13)C cross-polarization magic angle spinning solid-state spectroscopy, room-temperature and high-temperature X-ray powder diffraction, differential scanning calorimetry, and by analysis of weight loss, solvent content, powder density, morphology, and particle size. Solubility and intrinsic dissolution rates determined for the two polymorphic forms in water and hydrochloride solutions (HCl 0.1 N) were always higher for form II than for form I, which is actually the form used for the industrial preparation of NIC medicinal products. Preformulation studies might encourage industry for the evaluation of polymorph II, as it is more suitable for pharmaceutical applications. Results in drug delivery, as well as those obtained by the above-mentioned techniques, and the application of Burger-Ramberger's rules make it possible to conclude that there is a thermodynamic relation of monotropy between the two polymorphs. This last assumption may help formulators in predicting the relative stability of the two form