Praziquantel (PZQ) is an anthelmintic drug with low solubility, therefore cocrystallization and particle size reduction is desirable to improve bioavailability. In this study, a PZQ-malonic acid cocrystal was micronized by rapid expansion of supercritical solution (RESS). Due to low solubility in scCO2, 2 , four cosolvents were screened as RESS modifiers. While addition of acetone or THF yielded mixtures of PZQ and its cocrystal, MeOH and EtOH produced pure cocrystal. Impact of pressure (15-30 MPa), temperature (35-55 degrees C), and cosolvent loading (3-10 volumes) on phase-purity, yield, and particle size were investigated. Adding cosolvent to RESS facilitated dissolution of cocrystal formers in scCO2 2 and crystallization of the cocrystal with yields up to 68.5 wt% and particle size as low as 600 nm. Results show that for APIs with low solubility in scCO2, 2 , cosolvent-modified RESS is a suitable approach for simultaneous crystallization and micronization.

A cocrystal of niclosamide and urea was attempted for the first time using a crystallization in supercritical solvent (CSS). Experiments were conducted at 40 degrees C or 60 degrees C between 3.3 and 29.4 MPa in CO2. Cocrystal formation showed a dependence on the state of CO2 with no cocrystal formation below the critical point and consistently showed partial conversion above the critical point. The addition of 0.5 mL (2.7-3.5 mol%) cosolvent was found to have significant impact on cocrystal formation at 40 degrees C and 20 MPa. Addition of 2-propanol increased cocrystal formation by between 50 % and 60 % compared to neat scCO2, while cyclohexane reduced cocrystal formation by between 20 % and 35 %, and water completely hindered cocrystal formation. The impact of hold time, cosolvent, solubility in relation to ternary phase diagrams, and inter- and intra-molecular hydrogen bonding are discussed.

Supercritical carbon dioxide (CO2) has been used as a processing technique to control polymorphism of pharmaceuticals. However, there are fewer reports of novel polymorphs being discovered by supercritical CO2 processing. As supercritical crystallization methods gain attention for potential in pharmaceutical processing, they may become a critical screening tool for discovery of new polymorphs. In this work, a case study is presented for a novel crystalline form of the anthelmintic drug, Praziquantel, found through supercritical CO2 processing. The novel form of Praziquantel was characterized by chromatography, nuclear magnetic resonance and infrared spectroscopy, X-ray powder diffraction, thermal analysis, and scanning electron microscopy. Furthermore, the novel form exhibited 13-20% improved solubility compared to commercial Form A between pH 1.6 and 7.5 and was physically stable under stressed conditions (40 degrees C and 75% relative humidity) for 7.5 weeks. Overall, this work showed that supercritical CO2 processing is a valuable tool to screen for novel, and possibly viable polymorphs of pharmaceutical compounds with improved properties.

In this work, a ternary phase diagram was developed for a Niclosamide-urea co-crystal (NCS-UR) in isopropanol (IPA) using a combination of slurry and solvent addition methods. The ternary phase diagram showed that solubility of Niclosamide and urea differed by an order of magnitude in IPA, leading to an incongruently saturating system. Spray drying was explored as a method to generate NCS-UR. Co-crystals with small, uniform particle size were successfully prepared by spray drying from equimolar solutions with yield up to 73%. Co-crystals were phase pure by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) from all conditions explored. Somewhat similar particles were obtained at inlet temperature of 70 degrees C (mean size of 2.0 mm) compared to 85 degrees C (2.8-3.4 mm). Based on the TPD, isolating phase pure co-crystal through solution crystallization in IPA would require excess urea. However, spray drying did not require excess co-former. The in-vitro solubility of NCS-UR was compared to anhydrous NCS in biorelevant media. NCS-UR did not give improvement in solubility at 1 h or 24 h. Overall, this work showed that spray drying is a feasible process for preparing phase pure co-crystals for an incongruently saturating system and simultaneously generating micron size particles. (c) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Pharmaceuticals in Biopharmaceutics Classification System (BCS) Class II (low solubility, high permeability) are often modified to improve kinetic solubility. Co-crystallization and micronization are common methods for improving kinetic solubility. The basis of understanding co-crystallization processes is solubility and phase stability. In the majority of co-crystallizations, conventional solvents are utilized. Co-crystallization using supercritical carbon dioxide as a co-solvent and antisolvent can offer advantages over conventional co-crystallization including a greener solvent choice and the production of small, uniform particles without additional micronization. Gas antisolvent is the most widely reported supercritical fluid (SCF) co-crystallization process possibly due to its versatility in solvent selection and similarities to conventional antisolvent processes. This review focused on exploring critical co-crystallization parameters and feasibility of SCF techniques. In this review, it was identified that solvent choice proves to be one of the most critical parameters, impacting morphology, yield, phase purity, or polymorph to different extents. It was also identified that a systematic study of solubility to design co-crystallization processes is needed to optimize SCF co-crystallization yield and throughput. Furthermore, a focus on solubility and modeling of multicomponent systems and development of ternary phase diagrams can lead to robust, tailored co-crystallization processes in SCF systems, transitioning this technology to become more common in industry.

The present study describes a novel and scalable process for preparation of omega-3 and omega-6 fatty acids in solid form. The process involves multiple steps consisting of combining the oil with a metal base in alcohol to form a solution, followed by addition of reaction mixture to acetonitrile (anti-solvent) to form a slurry and further separating the solid through filtration. This process results in formation of a flowable solid with yield of 44-76% depending on the procedure employed. The fatty acid profile of the calcium and magnesium salts was stable after one year of storage in ambient conditions. The type of solvent and anti-solvent employed in such process has tremendous effect on the resulting solid texture, which could range from complete gum to a workable, filterable solid. It was also demonstrated that increasing the concentration of base in alcohol reduces the amount of residual acetonitrile in the solid.

SixSnyO1-x-y films with 0.45 < x < 0.80, 0.05 < y < 0.35, and 0.05 < ( 1-x-y) < 0.40 have been prepared using a magnetron sputtering method. All compositions had an amorphous structure and good capacity retention. Reversible volumetric capacities exceeding 2000 Ah/L were obtained in films with high Si or Sn content. The initial coulombic efficiency becomes reduced when the oxygen content is increased, as increasing the oxygen content in these films causes a reduction in reversible capacity. Surprisingly, however, the oxygen content does not substantially increase the irreversible capacity. Further work should focus on improving the initial coulombic efficiency of Si-Sn-O electrodes. (C) The Author(s) 2015. Published by ECS.

Fe-Si-Zn alloys prepared by ball milling were investigated as negative electrodes for Li-ion batteries. X-ray diffraction and room temperature Fe-57 Mossbauer measurements were used to characterize alloy structure. Electrochemistry of the alloys was determined at 30 degrees C. Formation of crystalline Li15Si4 was suppressed during cycling for compositions with greater than 10 at. % Fe. Unlike sputtered films of the same composition, the incorporation of Zn in these ball milled alloys did not suppress Li15Si4 formation. Instead, Zn behaved as if it were in a physical mixture with the other alloy components. This study shows that sputtered and ball milled alloys of the same composition can have very different electrochemical properties. (C) 2015 The Electrochemical Society.

Thin-film Fe–Zn libraries were investigated as negative electrode materials for Li-ion batteries using combinatorial and high-throughput techniques. X-ray diffraction, Mössbauer effect spectroscopy and electron microprobe were used to characterize the library structure. A new Fe–Zn phase with an unknown structure was observed in the ζ (FeZn13) region on the phase diagram. The electrochemistry of FexZn1−x (0.01<x<0.45) was studied at 30°C. The cycle life and coulombic efficiency improved as Fe concentration in electrodes increased to x=0.12. However, the capacity decreased as the iron content increased and the FexZn1−x alloys became completely inactive when the Fe content was above 12at.%. Ex-situ X-ray diffraction and Mössbauer measurements were used to explain the structural changes that occur during cycling. This is the first report of sputtered amorphous Fe–Zn alloys in the literature.

A thin film binary library of carbon-rich Fe1-xCx (0.47≤x≤0.97) alloys was prepared by combinatorial sputtering of carbon and iron. The sputtered library was characterized by X-ray diffraction and room temperature 57Fe Mössbauer effect spectroscopy to determine its microstructure. X-ray diffraction results show that the Fe1-xCx film is amorphous in the whole composition range of the library. For 0.52≤x≤0.59, a hyperfine field distribution and a quadrupole splitting distribution as obtained from Mössbauer spectra indicate the presence of a ferromagnetic phase and a paramagnetic phase in this regime. With increasing of carbon content, for 0.61≤x≤ 0.97, the sextet disappears and two paramagnetic doublets splitting appear suggesting two different Fe sites. The electrochemical performance of the Fe1-xCx film was investigated in lithium cells and the presence of Fe was found to increase the reversible capacity per mass of carbon over that of a pure carbon electrode.

Thin-film Fe-Si-Zn libraries were investigated as negative electrode materials for Li-ion batteries using combinatorial and high-throughput techniques. X-ray diffraction and electron microprobe measurements were used to characterize the library structure. A large amorphous region exists in Si-rich compositions of this system. The electrochemistry of numerous compositions of Fe-Si-Zn materials was determined near room temperature. Both Zn and Fe additions to Si were found to suppress the formation of Li15Si4 during cycling. (C) 2014 The Electrochemical Society. All rights reserved.

Bicellar dispersions of chain perdeuterated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC-d54) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) were prepared with the molar fraction of DHPC held fixed at 20% and varying amounts of DMPC replaced by the anionic lipid 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DMPG). (2)H NMR spectra were examined to assess the effect of added DMPG on mixture phase behavior and morphology. Quadrupole echo decay and quadrupole-Carr-Purcell-Mieboom-Gill echo train measurements provided information about slow motions contributing to echo decay in the high temperature phases. The spectra and quadrupole echo decay properties of DMPC-d54/DHPC (4:1) and DMPC-d54/DMPG/DHPC (3:1:1) were qualitatively similar. With increasing DMPG concentration, the transition between the magnetically orientable phase and the higher temperature phase became increasingly distinct, and the spectral shape and echo decay characteristics of the high temperature bicellar phase became increasingly similar to those of DMPC-d54 in the liquid crystalline phase. The observation that DMPG changes spectra in the orientable phase incrementally while increasing the distinction between the orientable and high temperature bicellar phases provides new insights into how DMPG influences bicellar mixture morphology.

The hydrophobic lung surfactant SP-B is essential for respiration. SP-B promotes spreading and adsorption of surfactant at the alveolar air-water interface and may facilitate connections between the surface layer and underlying lamellar reservoirs of surfactant material. SP-B63-78 is a cationic and amphipathic helical peptide containing the C-terminal helix of SP-B. (2)H NMR has been used to examine the effect of SP-B63-78 on the phase behavior and dynamics of bicellar lipid dispersions containing the longer chain phospholipids DMPC-d 54 and DMPG and the shorter chain lipid DHPC mixed with a 3∶1∶1 molar ratio. Below the gel-to-liquid crystal phase transition temperature of the longer chain components, bicellar mixtures form small, rapidly reorienting disk-like particles with shorter chain lipid components predominantly found around the highly curved particle edges. With increasing temperature, the particles coalesce into larger magnetically-oriented structures and then into more extended lamellar phases. The susceptibility of bicellar particles to coalescence and large scale reorganization makes them an interesting platform in which to study peptide-induced interactions between lipid assemblies. SP-B63-78 is found to lower the temperature at which the orientable phase transforms to the more extended lamellar phase. The peptide also changes the spectrum of motions contributing to quadrupole echo decay in the lamellar phase. The way in which the peptide alters interactions between bilayered micelle structures may provide some insight into some aspects of the role of full-length SP-B in maintaining a functional surfactant layer in lungs.