An exact model for predicting tablet and blend content uniformity based on the theory of fluctuations in mixtures.

Content uniformity (CU) of tablets is a critical property that needs to be well controlled in pharmaceutical products. Methods that predict the CU accurately can greatly help in reducing the development efforts. This article presents a statistical mechanical framework for predicting CU based on first principles at the molecular level.

Molecular dynamics simulations of functional group effects on solvation thermodynamics of model solutes in decane and tricaprylin.

Triglycerides and related fatty acid esters constitute a large percentage of the lipid excipients employed in the development of lipid-based drug formulations. Computer simulations can provide useful information on the structural, dynamic, and thermodynamic properties of these systems and may ultimately be valuable in predicting relative drug solubilities in lipid vehicles. This study utilized all-atom molecular dynamics simulations to explore the solvation of several model solutes in lipid vehicles.

Quantitative solubility relationships and the effect of water uptake in triglyceride/monoglyceride microemulsions.

Purpose: This paper aims to elucidate quantitative relationships between small molecule solubility/water-uptake in triglyceride/monoglyceride lipid formulations, the chemical structure of the solute, and the solvent composition.

Methods: Solubility and water uptake in tricaprylin/1-monocaprylin and tricaprylin/1-monocaprin mixtures in the "microemulsion" region at 37 degrees C were determined with HPLC and KF coulometry, respectively. Twelve model solutes varying in hydrogen bond acidity, basicity, polarity, and molecular volume were chosen.

What determines drug solubility in lipid vehicles: is it predictable?

Lipid-based drug delivery systems are of increasing interest to the pharmaceutical scientist because of their potential to solubilize drug molecules that may be otherwise difficult to develop. The ability to predict lipid solubility is an important step in being able to identify the right excipients to solubilize and formulate drugs in lipid formulations. However, predicting lipid solubility is complicated by the fact that interfacial effects may play a dominant role in these mixtures and the solubility may be affected by the microstructure (microemulsions, emulsions, oily solutions, etc.

Interior segment regrowth configurational-bias algorithm for the efficient sampling and fast relaxation of coarse-grained polyethylene and polyoxyethylene melts on a high coordination lattice.

We demonstrate the application of a modified form of the configurational-bias algorithm for the simulation of chain molecules on the second-nearest-neighbor-diamond lattice. Using polyethylene and poly(ethylene-oxide) as model systems we show that the present configurational-bias algorithm can increase the speed of the equilibration by at least a factor of 2-3 or more as compared to the previous method of using a combination of single-bead and pivot moves along with the Metropolis sampling scheme [N. Metropolis, A.

Calculation of pressure using the virtual-volume-variation method and the virial method from chain conformations obtained by Monte Carlo simulations on the second nearest neighbor diamond lattice.

For a model system of polyethylene of chain lengths 40 and 100 carbon atoms, we calculated the pressure at different densities and compared them with the experimental values. The simulation was conducted on the second nearest neighbor diamond lattice, and the pressure was calculated using the virtual-volume-variation method after the system was reverse mapped to its fully atomistic form in continuous space and energy minimized. In addition, the pressure was also calculated from the virial route by conducting a short molecular dynamics simulation starting from the energy minimized structure.

Modification of statistical threading in two-component pseudorotaxane melts using the amphiphilic approach and variations in the confinement geometry.

Recently we described a coarse-grained model of poly(ethylene oxide) and then employed that model to study the amount of spontaneous threading of cyclic molecules by linear chains in the melt [C. A. Helfer, G.

Significance of the free volume for metastability, spinodals, and the glassy state: an exact calculation in polymers.

A lattice model of semiflexible linear chains (with equilibrium polydispersity) containing free volume is solved exactly on a Husimi cactus. A metastable liquid (ML) is discovered to exist only at low temperatures and is distinct (and may be disjoint) from the supercooled liquid (SCL) that exists only at high temperatures. The free volume plays a significant role in that the spinodals of the ML and SCL merge and then disappear as the free volume is reduced.