Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this review is to weigh the current understanding of solid dispersion chemistry and to critically review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed.

An extensive study of the time dependence of DNA wrapping in single-walled nanotube (SWNT) dispersions has been carried out, revealing a number of unusual phenomena. SWNTs were dispersed in water with salmon testes DNA and monitored over a three-month period. Between 20 and 50 days after the sample was first prepared, the SWNT photoluminescence (PL) intensity was observed to increase by a factor of 50. This increase was accompanied by a considerable sharpening of the van Hove absorption peaks. High-resolution transmission electron microscopy (HRTEM) images showed the progressive formation of a coating of DNA on the walls of the nanotubes over the three-month period. HRTEM and circular dichroism spectroscopy studies showed that the improvement in both the NIR PL intensity and the van Hove absorption peaks coincided with the completion of a monolayer coating of DNA on the SWNT walls. HRTEM images clearly showed the DNA wrapping helically around the SWNTs in a surprisingly ordered fashion. We suggest that the initial quenching of NIR photoluminescence and broadening of absorption peaks is related to the presence of protonated surface oxides on the nanotubes. The presence of an ordered DNA coating on the nanotube walls mediates both deprotonation and removal of the surface oxides. An extensive DNA coating is required to substantially restore the photoluminescence, and thus, the luminescence switch-on and subsequent saturation indicate the completion of the DNA-wrapping process. The temperature dependence of the PL switch-on, and thus of the wrapping process, was investigated by measuring as functions of temperature both the time before PL switch-on and the time required for the PL intensity to saturate. This allowed the calculation of the activation energies for both the process preceding PL switch-on and the process limiting the rise of PL intensity, which were found to be 31 and 41 kJ mol (-1), respectively. The associated entropies of activation were -263 and -225 J mol (-1) K (-1), respectively. These negative activation entropies suggest that the rate-limiting step is characterized by a change in the system from a less-ordered to a more-ordered state, consistent with the formation of an ordered DNA coating.

Natural salmon testes DNA has been used to disperse single-walled carbon nanotubes (SWNTs) in water. It has been found that the primary factor controlling the nanotube bundle size distribution in the dispersion is the nanotube concentration. As measured by AFM, the mean bundle diameter tends to decrease with decreasing concentration. The number fraction of individual nanotubes increases with decreasing concentration. At low nanotube concentrations, number fractions of up to 83% individual SWNTs, equating to a mass fraction of 6.2%, have been obtained. Both the absolute number density and mass per volume of individual nanotubes initially increased with decreasing concentration, displaying a peak at ∼0.027 mg/mL. This concentration thus yields the largest quantities of individually dispersed SWNTs. The AFM data for populations of individual nanotubes was confirmed by infrared photoluminescence spectroscopy. The photoluminescence intensity increased with decreasing concentration, indicating extensive debundling. The concentration dependence of the luminescence intensity matched well to the AFM data on the number density of individual nanotubes. More importantly, it was found that, once initially dispersed, spontaneous debundling occurs upon dilution without the need for sonication. This implies that DNA-SWNT hybrids exist in water as a solution rather than a dispersion. The effects of dilution have been compared to the results obtained by ultracentrifuging the samples, showing dilution methods to be a viable and cost-effective alternative to ultracentrifugation. It was found that even after 4 h of ultracentrifugation at 122 000g, bundles with diameters of up to 4 nm remained in solution. The bundle diameter distribution after ultracentrifugation was very similar to the equilibrium distribution for the appropriate concentration after dilution, showing ultracentrifugation to be equivalent to dilution.

Stable dispersions of single-walled carbon nanotubes have been produced using the surfactant sodium dodecylbenzene sulfonate (SDBS). Atomic force microscopy analysis shows that, on dilution of these dispersions, the nanotubes exfoliate from bundles, resulting in a concentration-dependent bundle diameter distribution which saturates at D rms ≈ 2 nm for concentrations, C NT < 0.05 mg/mL. The total bundle number density increases with concentration, saturating at ∼6 bundles per μm3 for C NT > 0.05 mg/mL. As the concentration is reduced the number fraction of individual nanotubes grows, approaching 50% at low concentration. In addition, partial concentrations of individual SWNTs approaching 0.01 mg/mL can be realized. These values are far superior to those for solvent dispersions due to repulsion stabilization of the surfactant-coated nanotubes. These methods facilitate the preparation of high-quality nanotube dispersions without the need for ultracentrifugation, thus significantly increasing the yield of dispersed nanotubes.

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We have observed concentration dependent exfoliation of single-walled carbon nanotubes dispersed in solutions of the synthetic peptide nano-1. As the nanotube concentration is reduced, the bundle diameters tend to decrease before saturating at <2.0 nm for concentrations below 6 x 10(-3) mg/mL. The fraction of individual nanotubes increases with decreasing concentration, saturating at approximately 95% at low concentration. This concentration dependent exfoliation happens even if the dispersions are not sonicated on dilution, albeit over a longer time scale. The populations both of individual nanotubes and of bundles are much higher than expected at high concentrations, indicating the presence of repulsive internanotube interactions stabilizing the dispersions.

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