Search

In the current study, the influence of type of plasticizer used with Eudragit® RS 30D on the drug release was investigated in solid dosage form extrusion/spheronization, and film coating. The drug pellets were coated for controlling drug release with Eudragit® RS 30D containing dibutyl phthalate and compared with dibutyl sebacate as an alternative plasticizer. To study the influence of pH of the dissolution medium on the drug release profile, capsules are tested for drug release profile at pH 1.2, 4.4, and 6.3. Additionally, the aging effect on the curing of Eudragit® RS 30D is evaluated by exposing the capsules dosage form to room temperature (25 °C ± 2 °C/60% ± 5% RH) for time 0, 3, 6, and 9 months, accelerated temperature (40 °C ± 2 °C/75% ± 5% RH) for time 0, 3, and 6 months, and intermediate temperature (30 °C ± 2 °C/65% ± 5% RH) for time 0, 6, and 9 months. The replacement of dibutyl phthalate, with dibutyl sebacate for polymer coating system in similar concentration is comparable with respect to plasticization effect. The coalescence of the polymer particles is not changed and requires no additional processing parameter control or additional curing time. [ABSTRACT FROM AUTHOR]

The omega-3 fatty acid, alpha linolenic acid (ALA) found in plant-derived foods induces significant cardiovascular benefits when ingested. ALA may be cardioprotective during ischemia; however, the mechanism(s) responsible for this effect is unknown. Isolated adult rat cardiomyocytes were exposed to medium containing ALA for 24 h and then exposed to non-ischemic (control), simulated ischemia (ISCH), or simulated ischemia/reperfusion (IR) conditions. Cardiomyocyte phospholipids were extracted and analyzed by an HPLC/electrospray ionization tandem mass spectrometry system. Pre-treatment of cells with ALA resulted in a significant incorporation of ALA within cardiomyocyte phosphatidylcholine. Cell death, DNA fragmentation and caspase-3 activity increased during ischemia and ischemia/reperfusion. Two pro-apoptotic oxidized phosphatidylcholine (OxPC) species, 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) were significantly increased during both ischemia and ischemia/reperfusion. Pre-treatment of the cells with ALA resulted in a significant reduction in cell death during ischemia and ischemia/reperfusion challenge. Apoptosis was also inhibited during ischemia and ischemia/reperfusion as shown by reduced DNA fragmentation and decreased caspase activation. ALA pre-treatment significantly decreased the production of POVPC and PGPC during ischemia and ischemia/reperfusion. ALA pre-treatment also significantly increased in resting Ca during ischemia or ischemia/reperfusion but did not improve Ca transients. ALA protects the cardiomyocyte from apoptotic cell death during simulated ISCH and IR by inhibiting the production of specific pro-apoptotic OxPC species. OxPCs represent a viable interventional target to protect the heart during ischemic challenge. [ABSTRACT FROM AUTHOR]

Evaluation of hot-melt granulation of fenofibrate and croscarmellose sodium and its cooling time for the molten mass in a ratio of 55:45 was conducted to assess the manufacturing process capability to produce an acceptable granulation which flows well on Korsch PH300 tablet compression machine. The formation of the drug-polymer eutectic mixture was investigated by differential scanning calorimetry, scanning electron microscopy and X-ray powder diffraction. The physical properties of the hot-melt was determined by examining the milled blocks after solidification and milling after cooling periods of 10, 20 and 30 d. The milled material was assessed for the effect of hold time of the blend on the solid dose compression characteristics. The impact of cooling on the processing of the blocks was assessed after 10, 20 and 30 d of cooling. The study suggests that after the hot-melt formed the fenofibrate crystallized independently and a solid solution with croscarmellose sodium was not formed. The age of the blocks determined the hardness of the crystals, changing the processing nature of the granules with respect to compression and powder flow characteristics. The blocks processed after 20 d and beyond produced granules with a characteristic suitable for holding the blend for 14 d in the bin with no impact on flow properties and compressibility of the blend. There was no chipping, capping, sticking or picking observed and a higher compression speed was achieved. [ABSTRACT FROM AUTHOR]

The article presents a study that investigated the pharmacokinetics of cefoperazone after single intramuscular administration of 20 milligrams.kilograms-1 into the lateral neck region and its in vitro plasma protein binding in male cross bred calves. A standard microbiological assay technique using Escherichia coli was used to estimate the concentration of cefoperazone in plasma samples. The study found that the binding of cefoperazone to the plasma proteins of calves was weak and reversible.

The article presents information on a study which investigated the effect of paracetamol on the pharmacokinetics and dosage regimen of danofloxacin in buffalo calves. It details the materials and methodologies used in the study which include acclimatization of the animal sample, assaying of animal samples, and description of the plasma drug concentration plotted on semi logarithmic scale. It reveals the findings of the pharmacokinetics parameters of danofloxacin in healthy buffalo calves after its single and concomitant intramuscular administration with paracetamol.

In the current study, the influence of type of plasticizer used with Eudragit ® RS 30D on the drug release was investigated in solid dosage form extrusion/spheronization, and film coating. The drug pellets were coated for controlling drug release with Eudragit ® RS 30D containing dibutyl phthalate and compared with dibutyl sebacate as an alternative plasticizer. To study the influence of pH of the dissolution medium on the drug release profile, capsules are tested for drug release profile at pH 1.2, 4.4, and 6.3. Additionally, the aging effect on the curing of Eudragit ® RS 30D is evaluated by exposing the capsules dosage form to room temperature (25 °C ± 2 °C/60% ± 5% RH) for time 0, 3, 6, and 9 months, accelerated temperature (40 °C ± 2 °C/75% ± 5% RH) for time 0, 3, and 6 months, and intermediate temperature (30 °C ± 2 °C/65% ± 5% RH) for time 0, 6, and 9 months. The replacement of dibutyl phthalate, with dibutyl sebacate for polymer coating system in similar concentration is comparable with respect to plasticization effect. The coalescence of the polymer particles is not changed and requires no additional processing parameter control or additional curing time.

The recent introduction of novel anticancer therapies, including bevacizumab (BVZ) and sunitinib (SNT), is associated with an increased risk of cardiotoxicity. However, early identification of left ventricular (LV) systolic dysfunction may facilitate dose modification and avoid the development of advanced heart failure. Using a murine model of BVZ- and SNT-mediated cardiotoxicity, we investigated whether cardiac biomarkers and/or tissue velocity imaging (TVI) using echocardiography can detect early changes in cardiac function, before a decrease in LV ejection fraction is identified. A total of 75 wild-type C57Bl/6 male mice were treated with either 0.9% saline, BVZ, or SNT. Serial monitoring of blood pressure, high-sensitivity troponin I, and echocardiographic indexes were performed over a 14-day study period, after which the mice were euthanized for histological and biochemical analyses. Mice treated with either BVZ or SNT developed systemic hypertension as early as day 7, which increased by day 14. Cardiac biomarkers, specifically high-sensitivity troponin I, were not predictive of early LV systolic dysfunction. Although conventional LV ejection fraction values decreased at day 13 in mice treated with either BVZ or SNT, TVI confirmed early LV systolic dysfunction at day 8. Histological and biochemical analysis demonstrated loss of cellular integrity, increased oxidative stress, and increased cardiac apoptosis in mice treated with BVZ or SNT therapy at day 14. In a murine model of BVZ- or SNT-mediated cardiomyopathy, noninvasive assessment by TVI detected early LV systolic dysfunction before alterations in conventional echocardiographic indexes., (Copyright © 2015 the American Physiological Society.)