We report results from a molecular simulation study of the structure and dynamics of water near single carbohydrate molecules (glucose, trehalose, and sucrose) at 0 and 30 degrees C. The presence of a carbohydrate molecule has a number of significant effects on the microscopic water structure and dynamics. All three carbohydrates disrupt the tetrahedral arrangement of proximal water molecules and restrict their translational and rotational mobility. These destructuring effects and slow dynamics are the result of steric constraints imposed by the carbohydrate molecule and of the ability of a carbohydrate to form stable H bonds with water, respectively. The carbohydrates induce a pronounced decoupling between translational and rotational motions of proximal water molecules.

Abstract. Quality by design is an essential part of the modern approach to pharmaceutical quality. There is much confusion among pharmaceutical scientists in generic drug industry about the appropriate element and terminology of quality by design. This paper discusses quality by design for generic drugs and presents a summary of the key terminology. The elements of quality by design are examined and a consistent nomenclature for quality by design, critical quality attribute, critical process parameter, critical material attribute, and control strategy is proposed. Agreement on these key concepts will allow discussion of the application of these concepts to abbreviated new drug applications to progress.KEY WORDS: control strategy; critical material attributes; critical process parameters; design space; quality by design.

Abstract. Modeling and simulation of oral drug absorption have been widely used in drug discovery, development, and regulation. Predictive absorption models are used to determine the rate and extent of oral drug absorption, facilitate lead drug candidate selection, establish formulation development strategy, and support the development of regulatory policies. This review highlights the development of recent drug absorption models including dispersion and compartmental models. The compartmental models include the compartmental absorption and transit model; Grass model; gastrointestinal transit absorption model; advanced compartmental absorption and transit model; and advanced dissolution, absorption, and metabolism model. Compared to the early absorption models, the above models developed or extended since the mid-1990s have demonstrated greatly improved predictive performance by accounting for multiple factors such as drug degradation, gastric emptying, intestinal transit, first-pass metabolism, and intestinal transport. For future model development, more heterogeneous features of the gastrointestinal tract (villous blood flow, metabolizing enzymes, and transporters), food effects, and drug-drug interactions should be fully characterized and taken into consideration. Moreover, predicting population inter-and intravariability in oral drug absorption can be useful and important for the evaluation of clinical safety and efficacy of drugs. Establishing databases and libraries that contain accurate pharmaceutical and pharmacokinetic information for commercialized and uncommercialized drugs may also be helpful for model development and validation.KEY WORDS: advanced compartmental absorption and transit (ACAT) model; advanced dissolution, absorption, and metabolism (ADAM) model; compartmental model; dispersion model; oral drug absorption.

Differential scanning calorimetry (DSC) and infrared spectroscopy (IR) were used to study the thermal behavior of DNA as a function of water content up to 12 wpn (water molecules per nucleotide). The DSC and IR results show cooperativity of thermal DNA denaturation at 12 wpn. In the 3.3 to 7.2 wpn range, an early structural change involving slight disruption of base stacking arises, followed at higher temperature by a denaturation process where the major changes in backbone conformation occur. DNA thermal denaturation in the 3.3 to 12 wpn range is irreversible. However, structural disruptions caused by dehydration are fully reversible. The loss of the DNA ordered conformation upon dehydration leads to a decrease in the endothermic maximum that characterizes the thermal denaturation of DNA. At 3.3 wpn, the DNA loses most of its ordered conformation and undergoes a glasslike transition similar to the transition that denatured DNA experiences during reheating. The calorimetric manifestation of the glass transition is established for denatured DNA at low hydration through the study of water plasticizing effects on T g and enthalpy relaxation. At 1.0 wpn (the lowest water content achieved in this study), the DSC and IR data do not show any thermal or structural transitions, indicating the fully amorphous character of DNA at such low hydration.