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Hormesis
Published in T. D. Luckey, Radiation Hormesis, 2020
Hormology is the study of excitation. It includes physical, and chemical, as well as biologic vectors. One example is the melting point of a mixture of two metals. Addition of one to the other lowers the melting point until the eutectic point is reached; then adding more of the same metal to the mixture increases the melting point (Figure 2.3). This example shows clearly that small and large doses of a single agent evoke opposite effects.
Structures and Properties of Self-Assembled Phospholipids in Excess Water
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
When two phosopholipids are partially miscible in the gel phase and completely miscible in the fluid phase, the binary phase diagram may look like Figure 9B, which is for C( 18):C( 10)PC/C( 14):C( 14)PC mixtures.70 Such phase diagrams, constructed based on the onset and completion temperatures of phase transition curves obtained at various molar ratios of the mixtures, have a shape which is the hallmark of a eutectic system. In this system, there are three one-phase regions (G1, G2 and F), three two-phase regions (F + Gl5 F + G2 and Gi + G2), and one degenerated three-phase region, the eutectic point at a fixed temperature and composition. Of course, the three phases co-existing in equilibrium at the eutectic point are the maximum number of phases allowed to co-exist for the binary lipid mixtures, in excess water, at constant pressure according to the phase rule.66 In the case of C(18):C(10)PC/C(14):C(14)PC, the eutectic point is at 13.4°C and 40% of C(14):C(14)PC.
Ternary solid dispersions: classification and formulation considerations
Published in Drug Development and Industrial Pharmacy, 2021
Shambhavi Borde, Sagar Kumar Paul, Harsh Chauhan
The melting method, which is also known as the fusion method, is a simple and commonly used method for the production of solid dispersions. This process simply comprises the heating of materials followed by cooling. The components are melted together at a temperature above the eutectic point. The molecular mobility of this eutectic mixture is high enough to allow the drug particle to successfully occupy in the matrix, which results in decreased drug particle size and better wettability. In this process, the cooling rate is also crucial as it can affect the type of incorporation of the drug in the matrix [111]. This melted homogenous mixture is then solidified by different techniques, such as using a freezer, using an ice bath, spreading a thin layer on stainless steel cooled by air draft, spreading it on plates placed over dry ice, immersing in liquid nitrogen, or grinding the material in liquid nitrogen (cryo-grinding), pouring it into petri dishes placed at room temperature inside a desiccator [96]. For example, Pacult et al. prepared a D–D–P TSD by melting the physical mixture of materials on a hot plate and then vitrifying it by previously chilled copper plate [88]. After this, several other processes like crushing, pulverizing, and sieving are conducted to get the final solid dispersion powder.
Pharmaceutical cocrystal: a game changing approach for the administration of old drugs in new crystalline form
Published in Drug Development and Industrial Pharmacy, 2020
Prabhakar S. Panzade, Giridhar R. Shendarkar
Fernandes et al. reported the cocrystals of carvedilol with nicotinamide (1:2 ratio) via HME approach. The extrusion was performed using co-rotating twin-screw hot melt extruder (Do/Di) of 1.71. The four heating zones (B1, B2, B3, and B4) were created in the barrel and set at different temperatures (30, 85, 92, and 90 °C) at a screw speed of 175 rpm. The DSC study revealed that maintaining temperature above eutectic point is necessary for cocrystal synthesis. The product obtained was sticky and hard at screw speed of 100 rpm but at 75 rpm uniform size crystals were observed. The gravimetric screw feeder was employed to feed starting materials at a rate of 20 rpm. The selected processing variables like temperature and screw speed affected the cocrystallization hence were optimized. The obtained cocrystals exhibited distinct morphology, greater solubility, and dissolution than pure drug. Moreover, cocrystal yield was 86.26% with drug content of 99.09% showing the potential of the process to scale up [49].
Synthesis and characterization of meloxicam eutectics with mandelic acid and saccharin for enhanced solubility
Published in Drug Development and Industrial Pharmacy, 2020
Richard Perosa Fernandes, Ana Carina Sobral de Carvalho, Bruno Ekawa, Andre Luiz Soares Carneiro do Nascimento, Andressa Maria Pironi, Marlus Chorilli, Flávio Junior Caires
MLX, MND, SAC, and mixtures prepared by LAG method in molar ratio of 0.20, 0.25, 0.30, 0.34, 0.45, 0.5, 0.66, 0.75, and 0.80 of MLX were analyzed by DSC technique and the curves are shown in Figure 3. The enthalpy and melting temperature data obtained from DSC curves were used to plot binary phase diagrams and Tamman’s triangle, according to previous report of MLX [12]. Phase diagrams were plotted to screen the correct molar ratio of each eutectic mixture by comparing the melting point of each sample. A V-shaped pattern appears in eutectic phase diagram as a result of the low melting transition of the eutectic and its congruent melting compared to physical mixtures. The two lines demonstrate the solid and liquid points, the lines delimitate the regions at which the mixture is entirely solid (below solid line), a mixture of solid + liquid (between lines) or totally liquid (above liquid line) [9]. Enthalpy values were used to plot Tamman’s triangle to confirm the predicted eutectic point in each mole fraction. There is an increase in enthalpy until the eutectic mixture, that exhibit a maximum enthalpy value compared to others fractions, followed by a decrease [12].