| 1. |
- Ahuja, Dipali, et al.
(författare)
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Solution and calorimetric thermodynamic study of a new 1:1 sulfamethazine-3-methylsalicylic acid co-crystal
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033. ; 22:20, s. 3463-3473
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Tidskriftsartikel (refereegranskat)abstract
- A new 1:1 co-crystal of sulfamethazine (API, SMT) and 3-methylsalicylic acid (coformer, 3mSA) has been synthesized and its crystal structure solved by single crystal X-ray diffraction (XRD). The co-crystal has been thoroughly characterized by powder XRD, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The pure co-crystal could be synthesized by solvent drop grinding, cooling crystallization and slurry conversion co-crystallization. Ternary phase diagrams have been constructed in methanol and acetonitrile at 30 degrees C. The co-crystal exhibits incongruent dissolution in both solvents. The thermodynamics of co-crystal formation have been estimated from solubility data and calorimetric data, respectively, showing that formation of the SMT-3mSA co-crystal from its solid components is spontaneous and entropy-driven. The co-crystal formation is associated with a 5% increase in molecular volume. A relationship between the size of the region where the co-crystal is the most stable solid phase and the relative solubility of the co-crystal components has been uncovered. The co-crystal region becomes smaller as the solubility ratio increases.
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| 2. |
- Alemrajabi, Mahmood, 1989-, et al.
(författare)
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Separation of Rare-Earth Elements Using Supported Liquid Membrane Extraction in Pilot Scale
- 2022
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Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045.
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Tidskriftsartikel (refereegranskat)abstract
- The use of supported liquid membrane extraction for recovery and separation of rare-earth elements (REEs) has been investigated. Experiments have been carried out using the different configurations: (1) standard hollow fiber supported liquid membrane operation (HFSLM), (2) renewal liquid membrane operation (HFRLM), and (3) emulsion pertraction technology (EPT). The experiments were performed in pilot scale using a hollow fiber module with a mass transfer surface area of 8 m2. Synthetic feed solution was used with compositions based on a process for recovery of REE from an apatite concentrate. The total concentration of REE in the feed was varied from 1 to 22 mM REE and the pH was varied in the range 1.5–3.2. Di(2-ethylhexyl) phosphoric acid (D2HEPA) diluted in kerosene, 10% (v/v), was used as the organic membrane solution, and 3 M HCl was used as stripping solution. In supported liquid membrane extraction, the extraction performance is governed by both the kinetics of REE transport through the membrane and by thermodynamics. The effect of feed composition on the selectivity and transport of REE through the liquid membrane have been investigated. The results show that the liquid membrane is more selective toward the heavy REE at lower pH values and higher REE concentration. HFRLM shows a higher transport rate than HFSLM, while the HFSLM configuration gives a higher selectivity toward individual REE. The membrane performance in HFSLM configuration rapidly decays with time, while in the HFRLM and EPT configurations, the performance is much more stable. Possible mechanisms for decaying membrane performance are discussed, and gel formation is identified as being of significant importance. Gel formation is observed at an organic loading above ∼46% for Nd, 38% for Y, 46% for Dy, and 65% for Er. The work performed in this study serves as an initial step to demonstrate that HFRLM and EPT can provide stable operation and be feasible options for processing of REE liquors. A process flow diagram for the recovery of the REE, present in the apatite concentrate, in three fractions is proposed based on the results from this study.
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| 3. |
- Bergillos-Ruiz, Marta, et al.
(författare)
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Impact of carrier particle surface properties on drug nanoparticle attachment
- 2024
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 651
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Tidskriftsartikel (refereegranskat)abstract
- Hypothesis: The stabilization and isolation to dryness of drug nanoparticles has always been a challenge for nano-medicine production. In the past, the use of montmorillonite (MMT) clay carrier particles to adsorb drug nanoparticles and maintain their high surface area to volume ratio after isolation to dryness has proven to be effective. We hypothesise that the distribution of hydrophilic and hydrophobic patches on the clay's surface as well as its porosity/roughness, hinder the agglomeration of the drug nanoparticles to the extent that they retain their high surface area to volume ratio and display fast dissolution profiles. Experiments: In this work, the distribution of hydrophobicity and hydrophilicity, and the porosity/roughness, of the surface of selected silica carrier particles were varied and the impact of these variations on drug nanoparticle attachment to the carrier particle and subsequent dissolution profiles was studied. Findings: The fastest dissolution profiles at the highest drug nanoparticle loadings were obtained with a periodic mesoporous organosilane carrier particle which had a homogeneous distribution of hydrophobic and hydrophilic surface properties. Carrier particles with rough/porous surfaces and a combination of hydrophobic and hydrophilic patches resulted in nanocomposite powders with faster dissolution behaviour than carrier particles with predominantly either a hydrophobic or hydrophilic surface, or with non-porous/smoother surfaces.
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| 4. |
- Cheuk, Dominic, et al.
(författare)
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Influence of solvent on crystal nucleation of benzocaine
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033. ; 22:48, s. 8330-8342
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the solvent in nucleation of a polymorphic organic molecule, benzocaine, has been explored by measuring nucleation induction times, probing solvent-solute interactions in solution with spectroscopy and modelling the strength of solvent-solute intermolecular interactions using density functional theory (DFT). Over 2640 induction time experiments were conducted to study the crystal nucleation of benzocaine FII in six different organic solvents. The nucleation driving force required to reach the same induction time is strongly solvent-dependent, increasing in the order: ethyl acetate < 1,4-dioxane < acetonitrile < methanol < n-butanol. Nucleation in toluene is reasonably easy but the exact position varies with the induction time. The order between the solvents overall corresponds to the order of increasing interfacial energy as determined within the classical nucleation theory. The shift of the FTIR carbonyl frequency reflecting the strength in the solvent-solute interaction decreases in the same order as the interfacial energy of benzocaine FII increases. This shift is corroborated by DFT calculated energies of binding one solvent molecule to the carboxyl group of benzocaine. An even better correlation of the influence of the solvent on the nucleation is provided by DFT calculated energy of binding the complete first solvation shell to the benzocaine molecule. The different methods reveal a consistent picture and suggest that the stronger the solvent binds to the benzocaine molecule in solution, the slower the nucleation becomes.
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| 5. |
- Cheuk, Dominic, et al.
(författare)
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Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents
- 2020
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 109:11, s. 3370-3377
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Tidskriftsartikel (refereegranskat)abstract
- The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K-303 K (29 degrees C-30 degrees C). The polymorphs FI and FII have been characterised by infrared spectroscopy (IR), Raman spectroscopy, transmission powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC). The isobaric solid state heat capacities have been measured by DSC. The quantitative thermodynamic stability relationship has been determined in a comprehensive thermodynamic analysis of the calorimetric data. The solubility of both polymorphs has been determined in eight pure organic solvents over the temperature range 278 K-323 K by a gravimetric method. The mole fraction solubility of benzocaine decreases in the order: 1,4-dioxane, acetone, ethyl acetate, chloroform, acetonitrile, methanol, n-butanol and toluene. Comparison with the determined activity of solid benzocaine forms shows that negative deviation from Raoult's law ideality is found in dioxane, acetone and ethyl acetate solutions, and positive deviation in solutions of the other investigated solvents.
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| 6. |
- Diniz, Mariana O., et al.
(författare)
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New Solid Forms of Griseofulvin : A Solvate and a Relict Polymorph Related to Reported Solvates
- 2023
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 23:12, s. 8953-8961
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Tidskriftsartikel (refereegranskat)abstract
- This work presents two new solid forms, a polymorph and a solvate, of the antifungal active pharmaceutical ingredient griseofulvin (GSF). The novel forms were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The new polymorphic form (GSF Form VI) was obtained upon drying at room temperature the GSF-acetonitrile solvate. GSF Form VI is a relict structure related to reported solvates of GSF. Thermal stability studies show that Form VI is metastable and monotropically related to the stable GSF Form I. The new GSF-n-butyl acetate solvate was obtained by crystallization from an n-butyl acetate solution. The stoichiometry of the n-butyl acetate solvate is 1:0.5. The solvate loses the solvent from the crystal lattice at a temperature between 363.15 and 374.15 K.
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| 7. |
- Ghosh, Peuli, et al.
(författare)
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Impact of Additives on Drug Particles during Liquid Antisolvent Crystallization and Subsequent Freeze-Drying
- 2023
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Ingår i: Organic Process Research & Development. - : American Chemical Society (ACS). - 1083-6160 .- 1520-586X. ; 27:11, s. 2020-2034
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Tidskriftsartikel (refereegranskat)abstract
- The impact of single or combinations of additives on the generation of nanosuspensions of two poorly water-soluble active pharmaceutical ingredients (APIs), fenofibrate (FF) and dalcetrapib (DCP), and their isolation to the dry state via antisolvent (AS) crystallization followed by freeze-drying was explored in this work. Combinations of polymeric and surfactant additives such as poly(vinyl alcohol) or hydroxypropyl methyl cellulose and sodium docusate were required to stabilize nanoparticles (∼200-300 nm) of both APIs in suspension before isolation to dryness. For both FF and DCP, multiple additives generated the narrowest, most-stable particle size distribution, with the smallest particles in suspension, compared with using a single additive. An industrially recognized freeze-drying process was used for the isolation of these nanoparticles to dryness. When processed by the liquid AS crystallization followed by freeze-drying in the presence of multiple additives, a purer monomorphic powder for FF resulted than when processed in the absence of any additive or in the presence of a single additive. It was noted that all nanoparticles freeze-dried in the presence of additives had a flat, flaky habit resulting in large surface areas. Agglomeration occurred during freeze-drying, resulting in micron-size particles. However, after freeze-drying, powders produced with single or multiple additives showed similar dissolution profiles, irrespective of aging time before drying, thus attenuating the advantage of multiple additives in terms of size observed before the freeze-drying process.
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| 8. |
- Heffernan, C., et al.
(författare)
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Effects of structurally - related impurities on the crystal growth of curcumin spherulites
- 2022
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033. ; 24:28, s. 5156-5169
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Tidskriftsartikel (refereegranskat)abstract
- The crystal growth of curcumin in pure propan-2-ol and in this solvent containing two structurally related impurities, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), has been investigated by seeded isothermal desupersaturation experiments at 283, 293 and 308 K. In situ attenuated total reflectance UV-visible spectroscopy and focused beam reflectance measurement were used as process analytical technologies to monitor the solution concentration over time and to track the particle counts. Both impurities are found to slow down the growth of curcumin spherulites. The product particles collected after growth in the presence of the impurities present a rougher and more porous surface appearance in comparison to curcumin crystalline material grown in pure solutions. A detailed analysis of the powder X-ray diffraction patterns along with compositional analysis by high performance liquid chromatography of grown crystals reveals that impurities are not incorporated into the solid phase except at the highest impurity concentrations explored. By molecular modelling it is shown that the influence of impurities on the diffractograms of the material grown at high impurity concentrations is consistent with the formation of a solid solution. By fitting the Birth and Spread theory to the experimental growth data it is found that the interfacial energy for growth in the presence of the impurities is higher than that for growth of curcumin in the absence of impurities. Two scenarios are envisaged explaining the results. The first is that 3-D nucleation occurs on the impurity encumbered CUR crystallite generating new crystalline material on which crystal growth may continue. The second scenario envisages that a molecular cluster from the solution attaches to the impurity-encumbered surface and condenses into a crystalline surface nucleus without perfect lattice matching.
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| 9. |
- Heffernan, Claire, et al.
(författare)
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Growth kinetics of curcumin form I
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033. ; 22:20, s. 3505-3518
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Tidskriftsartikel (refereegranskat)abstract
- The growth rate of pure curcumin particles (CUR) in supersaturated propan-2-ol solutions has been determined by seeded isothermal desupersaturation experiments at different temperatures (283-318 K). In situ ATR UV-vis and FBRM were used to monitor the solution concentration over time and to verify that no nucleation was occurring. Principal component analysis (PCA) was applied to the UV-vis spectra to determine the supersaturation decay over time. The growth rate is examined by fitting the power law empirical models and the Burton Cabrera Frank (BCF) and birth and spread (B + S) mechanistic models to the experimental desupersaturation data. The growth rate is low, and the growth order (1.75) and the activation energy (38 kJ mol(-1)) are high, all suggesting that growth is surface integration controlled. Fitting the B + S model, the solid-liquid interfacial energy is estimated to be 2.7 mJ m(-2). Approximate surface diffusion rates are extracted and the mean surface diffusion distance is estimated to be 2 nm. The growth rate is clearly lower than that found for other compounds of lower molecular weight This originates from a higher interfacial surface energy and a slower surface diffusion.
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| 10. |
- Kakkar, Shubhangi, et al.
(författare)
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Characterization and Crystal Nucleation Kinetics of a New Metastable Polymorph of Piracetam in Alcoholic Solvents
- 2022
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 22:5, s. 2964-2973
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Tidskriftsartikel (refereegranskat)abstract
- A new polymorph of the drug active pharmaceutical ingredient piracetam (Form VI) has been discovered and characterized by X-ray powder diffraction (PXRD), solid-state Raman, attenuated total reflectance infrared spectroscopy, and differential scanning calorimetry. The PXRD diffractogram of Form VI shows a distinct peak at 24.2° (2θ) that distinguishes it from the previously known polymorphs and solvates. Form VI is metastable with respect to the previously known polymorphs Form II and Form III; in ethanol solution at 288 K, Form VI transforms into Form II within 15 min, while in isopropanol solution Form VI is kinetically stable for at least 6 h. A total of 1200 crystal nucleation induction time experiments of piracetam in ethanol and isopropanol solutions have been conducted, in sets of 40–80 repeat experiments carried out at different temperatures and solute concentrations. Each solution nucleated as a single polymorph, and each set of repeat experiments resulted in different proportions of Form II, Form III, and Form VI, with Form VI dominating at low nucleation temperatures and Form II at higher nucleation temperatures. The induction time data for Form VI at 288 K have been evaluated within the framework of the classical nucleation theory. At equal driving force, nucleation of Form VI is less obstructed in ethanol than in isopropanol, as captured by a lower interfacial energy and higher pre-exponential factor in ethanol. The proportion of Form VI obtained at a comparable driving force increases in the order ethanol < isopropanol.
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