Instant Controlled Pressure Drop technology: From a new fundamental approach of instantaneous transitory thermodynamics to large industrial applications on high performance–high controlled quality unit operations

Solvent extraction processes have been largely used in various industries. They recently were improved through new physical concepts such as CO₂ Supercritical Fluid Extraction, Ultrasound assisted process, Microwave-assisted extraction, Instant Controlled Pressure Drop DIC-assisted extraction… Systematically, a pretreatment stage of grinding takes place in order to improve the exchange surface increasing the starting accessibility. Swelling of the material structure implies an increase of the porosity thus leading to higher solvent diffusivity within the solid matrix. A new concept of expanded granule powder has recently been defined using Instant Controlled Pressure Drop DIC technology. Whatever the type of solvent is (even CO₂-SFE), such a swelled structure dramatically intensifies the kinetics through a higher specific exchange surface thanks to the open pores, while improving the solution solvent–solute diffusivity within the solid. Coupled to ultrasound, the internal transfer of solute within the pore solvent can likewise be intensified by replacing molecular diffusion within the pores by an effective convection transfer. In this work, we carried out a first approach of modeling of solvent extraction kinetics of expanded granules involving higher exchange surface and greater internal diffusion process.     

One injection for one-week controlled release: In vitro and in vivo assessment of ultrasound-triggered drug release from injectable thermoresponsive biocompatible hydrogels

Episodic release of bioactive compounds is often necessary for appropriate biological effects under specific physiological conditions. Here, we aimed to develop an injectable, biocompatible, and thermosensitive hydrogel system for ultrasound (US)-triggered drug release. An mPEG-PLGA-BOX block copolymer hydrogel was synthesized. The viscosity of 15 wt% hydrogel is 0.03 Pa*s at 25 °C (liquid form) and 34.37 Pa*s at 37 °C (gel form). Baseline and US-responsive in vitro release profile of a small molecule (doxorubicin) and that of a large molecule (FITC-dextran), from the hydrogel, was tested. A constant baseline release was observed in vitro for 7 d. When triggered by US (1 MHz, continuous, 0.4 W/cm²), the release rate increased by approximately 70 times. Without US, the release rate returned to baseline. Baseline and US-responsive in vivo release profile of doxorubicin was tested by subcutaneous injection in the back of mice and rats. Following injection into the subcutaneous layer, in vivo results also suggested that the hydrogels remained in situ and provided a steady release for at least 7 d; in the presence of the US-trigger, in vivo release from the hydrogel increased by approximately 10 times. Therefore, the mPEG-PLGA-BOX block copolymer hydrogel may serve as an injectable, biocompatible, and thermosensitive hydrogel system that is applicable for US-triggered drug release.     

Hexa-Coordinated Silicon Complexes Derived from Regioisomeric Aminotriphenylethanols and Their use as Dopants for Liquid Crystals

Abstract

Tridentate imine ligands that are obtained from the chiral, regioisomeric amino alcohols 2-amino-1,1,2-triphenyethanol and 2-amino-1,2,2-triphenylethanol serve for the formation of bis-chelated silicon complexes. Whereas the complex based on the former amino alcohol is obtained as a diastereomeric mixture, the complex that is derived from 2-amino-1,2,2-triphenylethanol forms in a completely diastereoselective manner, and its configuration is determined as (A,R,R), according to a crystal structure analysis. The new silicon complexes are found to be efficient dopants for the conversion of nematic liquid crystals into cholesteric phases.

GRAPHICAL ABSTRACT     

Molecular Chirality Recognized by Achiral Compounds

Abstract

Three cases are described where chirality is recognized by achiral molecules, where chirality is induced into achiral compounds through interactions with chiral compounds, and lastly where induced chirality in the solid-state is utilized for an enantio-selective photoreaction. In the first instance, the thermodynamically and kinetically preferred diastereoisomer of an optically labile chromium complex depended on the nature of the achiral solvent. In the second case, for the first time 1,2-chloroethane was trapped and observed in a chiral near-eclipsed form and 1-chloropropane in the truly eclipsed form at room temperature in a 1:1 inclusion complex with an optically active host molecule. Finally, induced chirality in a prochiral compound in the solid-state was successfully employed in an enantio-selective photoreaction. In the two cases, solid-state CD provided valuable information.     

Synthesis and Metal Ion Recognition Properties of a Novel Chiral Calix[4](azoxa)crown-7

A novel chiral calix[4](azoxa)crown-7 (9) has been synthesized and its metal ion recognition properties investigated. The starting reagents, chiral diamine 5 and calix[4]arene diacid chloride derivative 8, were prepared according to literature methods. ¹H and ¹³C NMR data show that 9 exists in a cone conformation. In liquid–liquid extraction experiments, 9 exhibits selectivity for Li⁺ among the other alkali metals and a good extraction ability for transition metal cations, suggesting its potential use in different fields, such as a sensor for ions as well as for chiral molecules.     

Recent developments in polymer–block–polypeptide and protein–polymer bioconjugate hybrid materials

In the last few years, polymer bioconjugates have been shown to be useful in many emerging areas of materials science. Consequently, the synthesis of polymer bioconjugates has suddenly become a central topic in polymer chemistry. The versatility and robust nature of modern synthetic methods such as controlled radical polymerisation (CLRP),¹ ring-opening polymerisation (ROP), and ‘click’ chemistry make them excellent tools for the preparation of tailor-made polymer bioconjugates. CLRP in combination with other techniques has been shown to be a mature technology for building tailor-made block copolymers and protein–polymer conjugates with a wide range of applications, especially in biomedical domains. This review describes the recent advances and progress in the rapidly expanding field of bioconjugation, outlining the work performed up to 2012.     

(Δ)[Fe(II)(phen)3]2+ Filled in the Chiral Cavitiy Constituted by {(Δ)[Fe(III)(C2O4)3](NH42+)(DMF)(H2O)32−}n

A chiral coordination compound {(Δ)[Fe(II)(phen)₃][(Δ)Fe(III)(C₂O₄)₃](NH₄)(H₂O)₃(DMF)}_n (phen = 1,10‐phenanthroline), (DMF = N,N'‐Dimethylformamide), has been synthesized, and the structure has been revealed by infrared spectroscopy and X‐ray single‐crystal diffraction. The framework consists of two chiral subunits. One subunit (Δ)[(Fe(III)(C₂O₄)₃]^3? which as host anion forms a chiral porous three‐dimensional supermolecular network with lattice water, lattice DMF and lattice ammonium cation through hydrogen bonds. And then the other is Δ[Fe(II)(phen)₃]²⁺ which as guest cation fills in the chiral cavity located in the previously mentioned host porous network.     

Surfactant-Free Multiple Pickering Emulsions Stabilized by Combining Hydrophobic and Hydrophilic Nanoparticles

A series of W/O/W or O/W/O emulsion stabilized solely by two different types of solid nanoparticles were prepared by a two-step method. We explored the option of particular emulsifiers for the multiple Pickering emulsions, and a variety of nanoparticles (silica, iron oxide, and clay) only differing in their wettability was used. The primary W/O emulsion was obtained by the hydrophobic nanoparticles, and then the hydrophilic nanoparticles were used as emulsifier in the secondary emulsification to prepare the W/O/W emulsion. In a similar way, the primary O/W emulsion of the O/W/O emulsion was stabilized by the hydrophilic nanoparticles, while the secondary emulsification to prepare the O/W/O emulsion was effected with the hydrophobic nanoparticles. The resultant multiple Pickering emulsion was stable to coalescence for more than 3 months, except the W/O/W emulsions of which the secondary emulsion stabilized by clay nanoparticles became a simple O/W emulsion in a day after preparation. Moreover, the temperature and pH sensitive poly(N-isopropylacrylamide-co-methacrylic acid) (P(NIPAm-co-MAA)) microgels were introduced as an emulsifier for the secondary emulsification to obtain the stimulus-responsive multiple W/O/W emulsion. Such microgel-stabilized multiple emulsions could realize the efficient controlled release of water-soluble dye, Rhodamine B (RB) on demand in a multiple-emulsion delivery system.      

Formulation and In Vitro Evaluation of Sustained Release Microspheres of Diltiazem Hydrochloride Prepared by Emulsification-Internal Gelation Method

The present work describes the formulation of alginate microspheres containing diltiazem hydrochloride by the emulsification-internal gelation method with the use of barium carbonate as a cross-linking agent. The effect of various factors (the concentration of alginate and barium chloride) on the drug loading efficiency and in vitro release were investigated. Fourier transform infrared microscopy (FTIR) and differential scanninig calorimetry (DSC) analysis confirmed the absence of any drug polymer interaction. X-ray diffraction (XRD) pattern showed that there is a decrease crystallinity of the drug. The in vitro drug release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from microcapsules. The stability studies of drug-loaded microcapsules showed that the drug was stable at different storage conditions.     

Synthesis of Per- and Poly-Substituted Trehalose Derivatives: Studies of Properties Relevant to Their Use as Excipients for Controlled Drug Release

Per- and poly-substituted oligosaccharide derivatives, with trehalose cores, have been prepared and assessed for their potential for use as excipients in controlled-release formulations. The synthesized compounds, generally with acyl and amido substituents, included 6,6′-N,N′ -diamido-6,6′ -dideoxy-α,α -trehalose derivatives, 6,6′ -bis(1,2,3,4-tetra-O-acetyl-β -D-glucopyranuronyl)-α, α -trehalose derivatives, 2,2′,3,3′ -tetra-O-acetyl-6,6′ -bis-(1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronyl)-4,4′ -di-O-acyl-α,α-trehalose, 2, 2′, 3, 3′ -tetra-O-acetyl-6-(1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronyl)-4,4′,6′ -tri-O-acyl-α,α-trehalose, and 2,2′,3,3′,4,4′ -hexa-O-acetyl-6,6′ -bis-(1,2,3,4-tetra-O-acetyl-6-O-succinyl-β-D-glucopyranuronyl)-α,α-trehalose. Compounds were characterized by NMR, IR, MS and optical rotations; elemental analyses; or HRMS. The compounds formed amorphous materials either on fast quenching of melts or on spray drying. Properties, used in the initial assessment of the potential as controlled-release excipients, were log₁₀ P and glass transition, T_g, values.