Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System

The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multicomponent ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behavior of ternary spray-dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulfate and poloxamer 188, and the model polymers used were polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray-dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behavior was observed for different formulations. The maximum supersaturation level was observed with drug–polymer–polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug–polymer) and ternary (drug–polymer–polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. On the basis of these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms

Dispersion and Exfoliation of Nanotubes with Synthetic Oligonucleotides: Variation of Dispersion Efficiency and Oligo-Nanotube Interaction with Base Type

Single walled carbon nanotubes (SWNTs) were dispersed and exfoliated in four different homopolymer oligonucleotides (dA15, dG15, dC15, and dT15). The dispersed nanotube concentration and degree of exfoliation were measured for each nucleobase. The nanotubes were more highly exfoliated and more temporally stable in dC15 and dT15. While the degree of exfoliation was relatively time independent, absorption and photoluminescence spectra showed definite changes over time after the initial sample preparation. In particular, photoluminescence signals appeared at well-defined times, consistent with previous evidence of time-dependent DNA wrapping followed by oxide removal. Analysis of the nanotubes’ optical properties, including circular dichroism, suggests that all bases except adenine stack onto the nanotube surface. In contrast, dA15 is unstable on the nanotube surface and eventually returns to a self-stacked arrangement. The order of the dispersion efficiencies was found to be T > C > G ≫ A, where thymine produced the most intense NT optical signals and cytosine was seen to wrap SWNTs the fastest

Spontaneous Exfoliation of Single-Walled Carbon Nanotubes Dispersed Using a Designed Amphiphilic Peptide

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 −3 mg/mL. The fraction of individual nanotubes increases with decreasing concentration, saturating at ∼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

Spontaneous Debundling of Single-Walled Carbon Nanotubes in DNA-Based Dispersions

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

Ordered DNA Wrapping Switches on Luminescence in Single-Walled Nanotube Dispersions

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

Large Populations of Individual Nanotubes in Surfactant-Based Dispersions without the Need for Ultracentrifugation

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 Drms ≈ 2 nm for concentrations, CNT < 0.05 mg/mL. The total bundle number density increases with concentration, saturating at ∼6 bundles per μm3 for CNT > 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