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Abstract  

We have established the phase diagram tolbutamide (TBM)-PEG 6000 and determined the eutectic composition 1/9 (w/w) in tolbutamide and melting temperature 56.2°C±0.3; no solid solution has been found. Negative mixing enthalpies of physical mixture (−2.5 J·g−1) and solid dispersions coprecipitate (−3.9 J·g−1) melt (−9.9 J·g−1) for eutectic composition involve the existence of interactions between drug and carrier. We have determined the dissolution kinetics: amount % dissolved (10 min) 65.87±0.55 (physical mixture), 78.02±0.02 (coprecipitate), 99.90±0.10 (melt). We have observed a good agreement between dissolution kinetics and mixing enthalpies data.

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Abstract  

The physical stability of amorphous drug in solid dispersion was estimated using differential scanning calorimetry (DSC). Tolbutamide (TB) and flurbiprofen (FBP) were selected as insoluble drugs in water. Polyvinylpyrrolidone (PVP) was selected as a polymer for solid dispersion. Solid dispersions of various ratios of TB or FBP and PVP-K25 were prepared by solvent evaporation method and the induction period of crystallization from amorphous drug in solid dispersion was measured by DSC. Compared with FBP, the induction period of crystallization from TB was delayed by an addition of PVP. The improvement of the physical stability by the addition of PVP-K25 was estimated from the activation energy of diffusion of drug molecules and the interfacial free energy between drug crystal and supercooled liquid of drug in solid dispersion. From thses results, the hindrance of the diffusivity of the drug molecule might be mainly affected the delay of the induction period of crystallization of TB and FBP.

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The chromatographic behavior of seven oral antidiabetic drugs — chlorpropamide, tolbutamide, glibenclamide, metformin, pioglitazone, rosiglitazone, and repaglinide — has been investigated. Normal-phase chromatography was performed on silica gel and alumina layers with mixtures of chloroform, diethyl ether, and ethyl acetate as mobile phases. For more effective resolution aqueous ammonia or acetic acid was added to the mobile phases. Silica gel enabled better separation than alumina. Reversed-phase chromatography was performed on octadecyl-bonded silica gel (RP-18) with mixtures of acetonitrile or 2-propanol with phosphate buffer as mobile phases. The effect of pH on the separation of the drugs was also examined. For separation of these drugs reversed-phase chromatography was more effective than use of normal-phase mode.

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of monogenic diabetes in children and adolescents. Pediatr. Diabetes, 2014, 15 (Suppl. 20), 47–64. 5 Fajans, S. S., Conn, J. W.: Tolbutamide-induced improvement in

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–548. [Hungarian] Jarrard, R. E., Wang, Y., Salyer, A. E., et al.: Potentiation of sulfonylurea action by an EPAC-selective cAMP analog in INS-1 cells: comparison of tolbutamide and gliclazide, and a potential role for EPAC

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tolbutamide and gliclazide, and a potential role for EPAC activation of a 2-APB sensitive Ca 2+ influx. Mol. Pharmacol., 2013, 83 (1), 191–205. Seino, S., Takahashi, H., Takahashi, T., et al.: Treating diabetes today: a

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tolbutamide [ 10 ] led by another undergraduate student, was presented by the undergraduate student at a national conference on thermal analysis in September 2005 as a podium presentation at the conference and manuscript on the conference disc. A third

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, Fernandes , CM , Carvalho , RA , Geraldes , FGC . Molecular modelling and 1H-NMR: ultimate tools for the investigation of tolbutamide: β-cyclodextrin and tolbutamide: hydroxypropyl-β-cyclodextrin complexes . Chem Pharm Bull . 2001 ; 49 : 10 1251

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Journal of Thermal Analysis and Calorimetry
Authors: Marcelo Kobelnik, Douglas Lopes Cassimiro, Clóvis. A. Ribeiro, Jorge M. V. Capela, Diogines S. Dias, and Marisa S. Crespi

amounts of metals on the polymorphism of tolbutamide . J Pharm Biomed Anal . 1996 ; 14 : 1069 – 1076 . 10.1016/S0731-7085(96)01784-0 .

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