Overview of milling techniques for improving the solubility of poorly water-soluble drugs

AbstractMilling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a “top–down” approach in the production of fine particles. Fine drug particulates are especially desired in formulations designed for parenteral, respiratory and transdermal use. Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents, often to enhance processability or solubility especially for drugs with limited aqueous solubility. The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size, specific surface area and shape of the drug particles as well as milling-induced amorphization and/or structural disordering of the drug crystal (mechanochemical activation). Technology advancements in milling now enable the production of drug micro- and nano-particles on a commercial scale with relative ease. This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs. Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement

A table-top femtosecond time-resolved soft x-ray transient absorption spectrometer

A laser-based, table-top instrument is constructed to perform femtosecond soft x-ray transient absorption spectroscopy. Ultrashort soft x-ray pulses produced via high-order harmonic generation of the amplified output of a femtosecond Ti:sapphire laser system are used to probe atomic core-level transient absorptions in atoms and molecules. The results provide chemically specific, time-resolved dynamics with sub-50-fs time resolution. In this setup, high-order harmonics generated in a Ne-filled capillary waveguide are refocused by a gold-coated toroidal mirror into the sample gas cell, where the soft x-ray light intersects with an optical pump pulse. The transmitted high-order harmonics are spectrally dispersed with a home-built soft x-ray spectrometer, which consists of a gold-coated toroidal mirror, a uniform-line spaced plane grating, and a soft x-ray CCD camera. The optical layout of the instrument, design of the soft x-ray spectrometer, and spatial and temporal characterization of the high-order harmonics are described. Examples of static and time-resolved photoabsorption spectra collected on this apparatus are presented

Femtosecond induced transparency and absorption in the extreme ultraviolet by coherent coupling of the He 2s2p (1P0) and 2p2 (1Se) double excitation states with 800 nm light

Femtosecond high-order harmonic transient absorption spectroscopy is used to observe electromagnetically induced transparency-like behavior as well as induced absorption in the extreme ultraviolet by laser dressing of the He 2s2p (1Po) and 2p2 (1Se) double excitation states with an intense 800 nm field. Probing in the vicinity of the 1s2 \to 2s2p transition at 60.15 eV reveals the formation of an Autler-Townes doublet due to coherent coupling of the double excitation states. Qualitative agreement with the experimental spectra is obtained only when optical field ionization of both double excitation states into the N = 2 continuum is included in the theoretical model. Because the Fano q-parameter of the unperturbed probe transition is finite, the laser-dressed He atom exhibits both enhanced transparency and absorption at negative and positive probe energy detunings, respectively.Comment: 18 pages, 5 figure

Towards the fabrication of phosphorus qubits for a silicon quantum computer

The quest to build a quantum computer has been inspired by the recognition of the formidable computational power such a device could offer. In particular silicon-based proposals, using the nuclear or electron spin of dopants as qubits, are attractive due to the long spin relaxation times involved, their scalability, and the ease of integration with existing silicon technology. Fabrication of such devices however requires atomic scale manipulation - an immense technological challenge. We demonstrate that it is possible to fabricate an atomically-precise linear array of single phosphorus bearing molecules on a silicon surface with the required dimensions for the fabrication of a silicon-based quantum computer. We also discuss strategies for the encapsulation of these phosphorus atoms by subsequent silicon crystal growth.Comment: To Appear in Phys. Rev. B Rapid Comm. 5 pages, 5 color figure

Capturing transient species in ionized liquid water and aqueous solutions

The ionization of liquid water serves as the principal trigger for a myriad of phenomena that are relevant to radiation chemistry and radiation biology. The earliest events that follow the ionization of water, however, remain relatively unknown. By employing few-cycle pulses in the visible to near-infrared (500 – 900 nm) and the short-wave infrared (0.9 – 1.7 μm), we have performed a comprehensive probe of the fate of the electron that is initially injected into the conduction band by ionization. The results suggest that the relaxation of the conduction band electron to the hydrated s electron proceeds via an intermediate state, whose lifetime is found to be 77 ± 6 fs (118 ± 7 fs) in H2O (D2O). In complementary experiments, femtosecond soft X-ray free-electron laser probing at the oxygen K edge is employed to track the primary proton transfer reaction of ionized liquid water [1]. The experimental results suggest that H2O+ first undergoes proton transfer to yield vibrationally excited OH on the timescale of 46 ± 10 fs. Subsequent vibrational relaxation of OH occurs with a time constant of 0.18 ± 0.02 ps. Our studies of ionized liquid water have also been extended to anion photodetachment in aqueous solution. For example, in the case of phenoxide, which serves as a model for the redox-active amino acid tyrosine, photodetachment launches vibrational wave packet motion along multiple vibrational modes of the phenoxyl radical product [2]. Analysis of the vibrational wave packet dynamics reveals the normal modes that drive structural reorganization upon photodetachment. Our results shed light on the elementary ultrafast dynamics that accompany the interaction of ionizing radiation with molecules of biological relevance.Published versio

Breakthroughs in photonics 2012 : attosecond electron dynamics

Advances in strong-field laser physics and ultrafast optics allow the study of ultrafast dynamics on electronic time scales. Here, recent developments from the past year in the field of attosecond electron dynamics are highlighted.Accepted versio

A table-top femtosecond time-resolved soft x-ray transient absorption spectrometer

A laser-based, table-top instrument is constructed to perform femtosecond soft x-ray transient absorption spectroscopy. Ultrashort soft x-ray pulses produced via high-order harmonic generation of the amplified output of a femtosecond Ti:sapphire laser system are used to probe atomic core-level transient absorptions in atoms and molecules. The results provide chemically specific, time-resolved dynamics with sub-50-fs time resolution. In this setup, high-order harmonics generated in a Ne-filled capillary waveguide are refocused by a gold-coated toroidal mirror into the sample gas cell, where the soft x-ray light intersects with an optical pump pulse. The transmitted high-order harmonics are spectrally dispersed with a home-built soft x-ray spectrometer, which consists of a gold-coated toroidal mirror, a uniform-line spaced plane grating, and a soft x-ray CCD camera. The optical layout of the instrument, design of the soft x-ray spectrometer, and spatial and temporal characterization of the high-order harmonics are described. Examples of static and time-resolved photoabsorption spectra collected on this apparatus are presented