Cocrystals of Hydrochlorothiazide: Solubility and Diffusion/Permeability Enhancements through Drug-Coformer Interactions

Hydrochlorothiazide (HCT) is a diuretic and a BCS class IV drug with low solubility and low permeability, exhibiting poor oral absorption. The present study attempts to improve the physicochemical properties of the drug using a crystal engineering approach with cocrystals. Such multicomponent crystals of HCT with nicotinic acid (NIC), nicotinamide (NCT), 4-aminobenzoic acid (PABA), succinamide (SAM), and resorcinol (RES) were prepared using liquid-assisted grinding, and their solubilities in pH 7.4 buffer were evaluated. Diffusion and membrane permeability were studied using a Franz diffusion cell. Except for the SAM and NIC cocrystals, all other binary systems exhibited improved solubility. All of the cocrystals showed improved diffusion/membrane permeability compared to that of HCT with the exception of the SAM cocrystal. When the solubility was high, as in the case of PABA, NCT, and RES cocrystals, the flux/permeability dropped slightly. This is in agreement with the expected interplay between solubility and permeability. Improved solubility/permeability is attributed to new drug-coformer interactions. Cocrystals of SAM, however, showed poor solubility and flux This cocrystal contains a primary sulfonamide dimer synthon similar to that of HCT polymorphs, which may be a reason for its unusual behavior. Hirshfeld surface analysis was carried out in all cases to determine whether a correlation exists between cocrystal permeability and drug-coformer interactions.

In-situ synthesized poly(vinyl butyral)/MMT-clay nanocomposites: The role of degree of acetalization and clay content on thermal, mechanical and permeability properties of PVB matrix

Poly(vinyl butyral) - MMT clay nanocomposites were synthesized in situ with three different degrees of acetalization and with varying clay content for each vinyl butyral polymer ratio. The clay nano-platelet galleries were expanded, as determined by X-ray diffraction and TEM analysis. The glass transition temperature of the polymer nanocomposites were found to be similar to 56 degrees C and similar to 52 degrees C for the neat polymer and the 4% clay loaded samples, respectively. The 4 wt% clay loaded film showed higher strength and low strain to failure. The dynamic mechanical analysis also confirmed the improved stability of the matrix. The matrix with 0.5 butyral to alcohol ratio for 4 wt% clay exhibited good water vapor transmission compared to all other compositions. The encapsulated devices with 2.5 and 4 wt% clay loaded films increases the device life time and the efficiencies of these films were 50% higher than their encapsulated pristine polymer films. (C) 2015 Elsevier Ltd. All rights reserved.

Permeability of Fractal Porous Media by Monte Carlo Simulations

The permeability of the fractal porous media is simulated by Monte Carlo technique in this work. Based oil the fractal character of pore size distribution in porous media, the probability models for pore diameter and for permeability are derived. Taking the bi-dispersed fractal porous media as examples, the permeability calculations are performed by the present Monte Carlo method. The results show that the present simulations present a good agreement compared with the existing fractal analytical solution in the general interested porosity range. The proposed simulation method may have the potential in prediction of other transport properties (such as thermal conductivity, dispersion conductivity and electrical conductivity) in fractal porous media, both saturated and unsaturated.

Transient Flows in Low Permeability Porous Media with Composite Start-Up Pressure Gradient

A new mathematical model for the transient flow in the composite low permeability is established. It is solved by FEM with different boundary conditions such as infinite, circular closed and constant pressure boundary conditions. The typical curves for transient wellbore pressure have been presented. It is shown that the pressure and pressure derivative curves with composite start-up pressure gradients have different slopes which are depended on the start-up pressure gradients and the mobility radios in different regions. The boundary effects are the same as the normal reservoirs without start-up pressure gradients. The study provides a new tool to analyze the transient pressure test data in the low permeability reservoir.