Solubility and dissolution enhancement strategies: current understanding and recent trends

Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade.     

Propellant Gas Phase Chemical Kinetics

An adiabatic constant pressure chemical kinetic study of the AP gas phase is conducted. The objective is to examine the importance of chemical kinetic studies for propellant deflagration modelling in general and for AP in particular. A reaction mechanism consisting of ninety five elementary reactions involving twenty one chemical species is developed to represent the AP gas phase. An important parameter that can be obtained from the kinetics is the time rate of change of temperature of the gas phase at the condensed phase-gas phase boundary (dT/dt at t = 0). This is directly related to the heat feedback from the gas phase to the condensed phase. Comparison with earlier work indicates that the use of a one-step overall reaction could lead to underestimates of heat feedback from the gas phase by a factor of about four. In addition it is found that the rate of decrease of dT/dt at t = 0, with pressure is much larger at lower pressures, suggesting a possible gas phase role in the low pressure deflagration limit. Further, the kinetic study does not support the conclusion of a constant fraction of AP reacting in the condensed phase in the pressure range 20–100 atmospheres. These results are at variance with what is obtained by use of a one-step overall reaction. Thus, the one-step overall reaction cannot represent even qualitatively several gas phase characteristics important for deflagration studies, and its use leads to erroneous results. It is concluded that a full reaction mechanism representation of gas phase chemical kinetics is essential to AP deflagration modelling. The same conclusion is probably valid for propellant deflagration modelling in general.     

Energetics of Propellants,Fuels and Explosives; a chemical valence approach

A simple approach involving the chemical valences of the fuel and the oxidizer elements present in a combustible mixture is described to evaluate the energetics related parameters of propellants, fuels and explosives. It simplifies the stoichiometric balancing of complex combustion equations, and provides an easy method of calculating the elemental stoichiometric coefficient. The method correctly predicts whether a mixture is fuel-lean, fuel-rich or stoichiometrically balanced. The calorimetric value of various stoichiometrically balanced combustible systems has been shown to be linearly dependent upon their total oxidizing (or reducing) valences. This relationship has been used successfully to evaluate the calorific value of fossil fuels. For fuel-rich explosives, a new valence dependent parameter has been derived which is found to be related with properties such as detonation velocity, heat of explosion and impact sensitivity.     

Analytic solution for planar indeterminate impact problems using an energy constraint

This work proposes an analytic method for resolving planar multi-point indeterminate impact problems for rigid-body systems. An event-based approach is used to detect impact events, and constraints consistent with the rigid-body assumption are used to resolve the indeterminacy associated with multi-point impact analysis. The work-energy relation is utilized to determine post-impact velocities based on an energetic coefficient of restitution to model energy dissipation, thereby yielding an energetically consistent set of post-impact velocities based on Stronge’s energetic coefficient of restitution for the treatment of rigid impacts. The effect of stick–slip transition is analyzed based on Coulomb friction. This paper also discusses the transition from impact to contact. This analysis is essential for considering the rocking block problem that is used as an example herein. The predictions of the model for the rocking block problem are compared to experimental results published in the literature. An example of a planar ball undergoing two-point impact is also presented.     

Thermal-aware task allocation and scheduling for periodic real-time applications in mesh-based heterogeneous NoCs

Real-Time Systems - With continuous technology scaling, the power density and hence the temperature of Network-on-Chip (NoC) may increase rapidly. This in-turn degrades the performance of the chip...     

Performance evaluation of breast lesion detection systems with expert delineations: a comparative investigation on mammographic images

Multimedia Tools and Applications - Performance of computerized diagnostic systems yearning to be approved by medical regulatory bodies must meet the expectations of human experts. Highly accurate...     

Steam drum level dynamics in a multiple loop natural circulation system of a pressure-tube type boiling water reactor

Advanced Heavy Water Reactor (AHWR) is a pressure tube type boiling water reactor employing natural circulation as the mode of heat removal under all the operating conditions. Main heat transport system (MHTS) of AHWR is essentially a multi-loop natural circulation system with all the loops connected to each other. Each loop of MHTS has a steam drum that provides for gravity based steam–water separation. Steam drum level is a very critical parameter especially in multi-loop natural circulation systems as large departures from the set point may lead to ineffective separation of steam–water or may affect the driving head. However, such a system is susceptible to steam drum level anomalies under postulated asymmetrical operating conditions among the different quadrants of the core like feedwater flow distribution anomaly among the steam drums or power anomaly among the core quadrants. Analyses were carried out to probe such scenarios and unravel the underlying dynamics of steam drum level using system code RELAP5/Mod3.2. In addition, a scheme to obviate such problem in a passive manner without dependence on level controller was examined. It was concluded that steam drums need to be connected in the liquid as well as steam space to make the system tolerant to asymmetrical operating conditions.