A high molecular weight silk fibroin scaffold that resists degradation and promotes cell proliferation.

The regulation of the biodegradation rate of 3D-regenerated silk fibroin scaffolds and the avoidance of premature collapse are important concerns for their effective applications in tissue engineering. In this study, bromelain, which is specific to sericin, was used to remove sericin from silk, and high molecular weight silk fibroin was obtained after the fibroin fibers were dissolved. Afterwards, a 3D scaffold was prepared via freeze-drying. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis results showed that the average molecular weight of the regenerated silk fibroin prepared by using the bromelain-degumming method was approximately 142.2 kDa, which was significantly higher than that of the control groups prepared by using the urea- and Na2 CO3 -degumming methods. The results of enzyme degradation in vitro showed that the biodegradation rate and internal three-dimensional structure collapse of the bromelain-degumming fibroin scaffolds were significantly slower than those of the two control scaffolds. The proliferation activity of human umbilical vein vascular endothelial cells inoculated in bromelain-degumming fibroin scaffolds was significantly higher than that of the control scaffolds. This study provides a novel preparation method for 3D-regenerated silk fibroin scaffolds that can effectively resist biodegradation, continuously guide cell growth, have good biocompatibility, and have the potential to be used for the regeneration of various connective tissues.

Magnetic properties of a soft magnetic elastomer based on antioxidant magnetic composite particles and a water-soluble polymer matrix.

A soft magnetic elastomer, called a magnetorheological elastomer (MRE), based on a polyacrylamide (PAM) modified carbonyl iron particle (P-CIP) composite and a water-soluble PAM matrix was designed and prepared by the chemical polymerization and crosslinking method. P-CIPs were synthesized by the polymerization of an acrylamide monomer on the CIP surface to improve the oxidation resistance of CIPs and the interaction between the particles and polymer matrix in the MRE. The results obtained from infrared spectroscopy, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) (in a nitrogen atmosphere) show that the coating effect of the polymer on the particle surface is very good. TGA (in an air atmosphere) curves indicate that the P-CIPs show strong oxidation resistance. Meanwhile, the test results obtained for the magnetic properties show that the MRE with P-CIPs has a saturation magnetization (94.7 emu g-1), a relative magnetorheological effect (687.5%), and a Payne effect factor (92%) under the action of a strong magnetic field (1 T). It was also clearly found that these properties are enhanced with increasing magnetic field intensity. Furthermore, the chain effect of magnetic particles under a magnetic field, the strong particle-matrix interaction and its breakdown process with increasing shear strain were discussed in this work.

Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition.

OBJECTIVES: Polymeric excipients play an important role in a cocrystal formulation to act as precipitation inhibitors to maximize the potential. Otherwise, a stable form of the parent drug will be recrystallized on the dissolving cocrystal surface and/or in the bulk solution during the cocrystal dissolution process, negating the solubility advantage. The objectives of this work were to investigate the potential of using combined polymers to maximise the dissolution performance of surface precipitation pharmaceutical cocrystals. METHODS: The dissolution performance of a highly soluble flufenamic acid and nicotinamide (FFA-NIC) cocrystal has been systematically studied with predissolved or powder mixed with a single polymer, including a surface precipitation inhibitor [i.e., copolymer of vinylpyrrolidone (60%) /vinyl acetate (40%) (PVP-VA)] and two bulk precipitation inhibitors [i.e., polyethylene glycol (PEG) and Soluplus (SLP)], or binary polymers combinations. RESULTS: A single polymer of PVP-VA prevented the FFA surface precipitation for an enhanced dissolution performance of FFA-NIC cocrystal. Unfortunately, it cannot sustain the supersaturated FFA concentration in the bulk solution. A combination of two polymers of PVP-VA and SLP has shown a synergistic inhibition effect to enhance the dissolution advantage of FFA-NIC cocrystal. CONCLUSIONS: The dissolution of a cocrystal with surface precipitation of the parent drug can be described as: i) the cocrystal surface contacting the dissolution medium; ii) the cocrystal surface dissolving; iii) the parent drug precipitation on the dissolving surface; and iv) the parent drug particles redissolving. A combination of two types of polymers can be used to maximise the cocrystal performance in solution.

Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.

OBJECTIVES: Miltefosine is the first and only oral medication to be successfully utilized as an antileishmanial agent. However, the drug is associated with differences in exposure patterns and cure rates among different population groups e.g. ethnicity and age (i.e., children v adults) in clinical trials. In this work, mechanistic population physiologically-based pharmacokinetic (PBPK) models have been developed to study the dose-exposure-response relationship of miltefosine in in silico clinical trials and evaluate the differences in population groups, particularly children and adults. METHODS: The Simcyp population pharmacokinetics platform was employed to predict miltefosine exposure in plasma and peripheral blood mononuclear cells (PBMCs) in a virtual population under different dosing regimens. The cure rate of a simulation was based on the percentage of number of the individual virtual subjects with AUCd0-28 > 535 µg⋅day/mL in the virtual population. RESULTS: It is shown that both adult and paediatric PBPK models of miltefosine can be developed to predict the PK data of the clinical trials accurately. There was no significant difference in the predicted dose-exposure-response of the miltefosine treatment for different simulated ethnicities under the same dose regime and the dose-selection strategies determined the clinical outcome of the miltefosine treatment. A lower cure rate of the miltefosine treatment in paediatrics was predicted because a lower exposure of miltefosine was simulated in virtual paediatric in comparison with adult virtual populations when they received the same dose of the treatment. CONCLUSIONS: The mechanistic PBPK model suggested that the higher fraction of unbound miltefosine in plasma was responsible for a higher probability of failure in paediatrics because of the difference in the distribution of plasma proteins between adults and paediatrics. The developed PBPK models could be used to determine an optimal miltefosine dose regime in future clinical trials.

Direct Probing of the Oxygen Evolution Reaction at Single NiFe2O4 Nanocrystal Superparticles with Tunable Structures.

Due to the precisely controllable size, shape, and composition, self-assembled nanocrystal superlattices exhibit unique collective properties and find wide applications in catalysis and energy conversion. Identifying their intrinsic electrocatalytic activity is challenging, as their averaged properties on ensembles can hardly be dissected from binders or additives. We here report the direct measurement of the oxygen evolution reaction at single superparticles self-assembled from ∼8 nm NiFe2O4 and/or ∼4 nm Au nanocrystals using scanning electrochemical cell microscopy. Combined with coordinated scanning electron microscopy, it is found that the turnover frequency (TOF) estimated from single NiFe2O4 superparticles at 1.92 V vs RHE ranges from 0.2 to 11 s-1 and is sensitive to size only when it is smaller than ∼800 nm in diameter. After the incorporation of Au nanocrystals, the TOF increases by ∼6-fold and levels off with further increasing Au content. Our study demonstrates the first direct single entity electrochemical study on individual nanocrystal superlattices with tunable structures and unravels the intrinsic structure-activity relationship that is not accessible by other methods.

All-Graphitic Multilaminate Mesoporous Membranes by Interlayer-Confined Molecular Assembly.

Layered mesostructured graphene, which combines the intrinsic advantages of planar graphene and mesoporous materials, has become interestingly important for energy storage and conversion applications. Here, an interlayer-confined molecular assembly method is presented for constructing all-graphitic multilaminate membranes (MMG⊂rGO), which are composed of monolayer mesoporous graphene (MMG) sandwiched between reduced graphene oxide (rGO) sheets. Hybrid assembly of iron-oleate complexes and organically modified GO sheets enables the preferential assembly of iron-oleate precursors at the interlayer space of densely stacked GO, driven by the like-pair molecular van der Waals interactions. Confined pyrolysis of iron-oleate complexes at GO interlayers leads to close-packed, carbon-coated Fe3 O4 nanocrystal arrays, which serve as intermediates to template the subsequent formation of MMG⊂rGO membranes. To demonstrate their application potentials, MMG⊂rGO membranes are exploited as dual-functional interlayers to boost the performance of Li-S batteries by concurrently suppressing the shuttle of polysulfides and the growth of Li dendrites. This work showcases the capability of molecular-based hybrid assembly for synthesizing multilayer mesostructured graphene with high packing density and its use in electrochemical energy applications.

Artemisinin Cocrystals for Bioavailability Enhancement. Part 1: Formulation Design and Role of the Polymeric Excipient.

Artemisinin (ART) is a most promising antimalarial agent, which is both effective and well tolerated in patients, though it has therapeutic limitations due to its low solubility, bioavailability, and short half-life. The objective of this work was to explore the possibility of formulating ART cocrystals, i.e., artemisinin-orcinol (ART-ORC) and artemisinin-resorcinol (ART2-RES), as oral dosage forms to deliver ART molecules for bioavailability enhancement. This is the first part of the study, aiming to develop a simple and effective formulation, which can then be tested on an appropriate animal model (i.e., mouse selected for in vivo study) to evaluate their preclinical pharmacokinetics for further development. In the current work, the physicochemical properties (i.e., solubility and dissolution rate) of ART cocrystals were measured to collect information necessary for the formulation development strategy. It was found that the ART solubility can be increased significantly by its cocrystals, i.e., 26-fold by ART-ORC and 21-fold by ART2-RES, respectively. Screening a set of polymers widely used in pharmaceutical products, including poly(vinylpyrrolidone), hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose acetate succinate, based on the powder dissolution performance parameter analysis, revealed that poly(vinylpyrrolidone)/vinyl acetate (PVP-VA) was the most effective crystallization inhibitor. The optimal concentration of PVP-VA at 0.05 mg/mL for the formulation was then determined by a dissolution/permeability method, which represented a simplified permeation model to simultaneously evaluate the effects of a crystallization inhibitor on the dissolution and permeation performance of ART cocrystals. Furthermore, experiments, including surface dissolution of single ART cocrystals monitored by Raman spectroscopy, scanning electron microscopy and diffusion properties of ART in solution measured by 1H and diffusion-ordered spectroscopy nuclear magnetic resonance spectroscopy, provided insights into how the excipient affects the ART cocrystal dissolution performance and bioavailability.

Artemisinin Cocrystals for Bioavailability Enhancement. Part 2: In Vivo Bioavailability and Physiologically Based Pharmacokinetic Modeling.

We report the evaluation and prediction of the pharmacokinetic (PK) performance of artemisinin (ART) cocrystal formulations, that is, 1:1 artemisinin/orcinol (ART-ORC) and 2:1 artemisinin/resorcinol (ART2-RES), using in vivo murine animal and physiologically based pharmacokinetic (PBPK) models. The efficacy of the ART cocrystal formulations along with the parent drug ART was tested in mice infected with Plasmodium berghei. When given at the same dose, the ART cocrystal formulation showed a significant reduction in parasitaemia at day 4 after infection compared to ART alone. PK parameters including Cmax (maximum plasma concentration), Tmax (time to Cmax), and AUC (area under the curve) were obtained by determining drug concentrations in the plasma using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), showing enhanced ART levels after dosage with the cocrystal formulations. The dose-response tests revealed that a significantly lower dose of the ART cocrystals in the formulation was required to achieve a similar therapeutic effect as ART alone. A PBPK model was developed using a PBPK mouse simulator to accurately predict the in vivo behavior of the cocrystal formulations by combining in vitro dissolution profiles with the properties of the parent drug ART. The study illustrated that information from classical in vitro and in vivo experimental investigations of the parent drug of ART formulations can be coupled with PBPK modeling to predict the PK parameters of an ART cocrystal formulation in an efficient manner. Therefore, the proposed modeling strategy could be used to establish in vitro and in vivo correlations for different cocrystals intended to improve dissolution properties and to support clinical candidate selection, contributing to the assessment of cocrystal developability and formulation development.

High-power cylindrical vector beams generated from an all-fiber linearly polarized laser by metasurface extracavity conversion.

Five-hundred-watt cylindrical vector beams (CVBs) at 1030 nm with the 3 dB linewidth being less than 0.25 nm have been generated from a narrow linewidth all-fiber linearly polarized laser by metasurface extracavity conversion. At maximum output power, the transmission efficiency and polarization extinction ratio of radially polarized cylindrical vector beams (RP-CVBs) are beyond 98% and 95%, respectively. The average power is approximately an order higher than previously reported high-power narrow-linewidth CVBs generated from fiber lasers. The temperature rise of the metasurface is less than 10°C at 500 W output power, which means that the system can be further power-scaled in the near future. The high-power, high-purity, and high-efficiency RP-CVBs generated by the metasurface demonstrate potential application of a metasurface in high-power CVBs lasers.

Understanding the Effects of a Polymer on the Surface Dissolution of Pharmaceutical Cocrystals Using Combined Experimental and Molecular Dynamics Simulation Approaches.

The molecular interactions between the surfaces of cocrystals [i.e., flufenamic acid and theophylline (FFA-TP), flufenamic acid and nicotinamide (FFA-NIC), and carbamazepine and nicotinamide (CBZ-NIC)] and the polymers [i.e., polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinylpyrrolidone (60%)/vinyl acetate (40%) (PVP-VA)] were investigated through combined experimental and molecular dynamics simulation approaches to resolve the mechanisms of cocrystal dissolution and precipitation. It was found that adsorption of the polymers on the surfaces of cocrystals might prevent the precipitation of the parent drug and alter the dissolution rate. The effect of polymers on precipitation could be determined by the cocrystal dissolution rate, the interactions of polymers with the surfaces of cocrystals, the characters of the noncovalent bonds formed between the polymers and the cocrystal surfaces, and the mobility and conformation of the polymers. The etching experiments of single cocrystals revealed that FFA-NIC and CBZ-NIC appeared as surface precipitation cocrystals while FFA-TP could lead to bulk precipitation. Both PVP and PVP-VA were good precipitation inhibitors for FFA-NIC, and they could completely inhibit the recrystallization of FFA III on the surfaces of dissolving cocrystals. In addition, as the adsorption of the polymer was slower than dissolution rate of the cocrystals, PVP and PVP-VA could only partially inhibit the recrystallization of CBZ dihydrate on the surface of CBZ-NIC. While PEG had no inhibitory effect on the surface crystallization of FFA-NIC and CBZ-NIC, due to its weak interactions with the surfaces of the cocrystals, it enhanced the dissolution performance of FFA-TP. In contrast, PVP and PVP-VA reduced the dissolution rate of FFA-TP and subsequently undermined the performance of cocrystals. Taken together, the approach of combining experimental and molecular dynamics simulation provided insights into the mechanisms of cocrystal dissolution as well as the polymers acting as inhibitory excipients for precipitation/recrystallization, making contribution to the development of novel formulations.

Effects of Solid Precipitation and Surface Corrosion on the Adhesion Strengths of Sintered Hydrate Deposits on Pipe Walls.

A hydrate directly growing and sintering on a pipe wall is an important hydrate deposition case that has been relatively unexplored. In the present study, the adhesion strengths of a sintered cyclopentane (CyC5) hydrate deposit under different solid precipitation and surface corrosion conditions were measured and discussed. It was found that the hydrate adhesion strengths increased by 1.2-1.5× when the soaking time of the carbon steel substrate in a 5 wt % NaCl solution increased from 24 to 72 h, which reduced the water wetting angle from 112 ± 3.5° to 94 ± 3.3°. The wax coating reduced the strength of CyC5 hydrate adhesion by up to nearly 20-fold by reversing the substrate wettability and affecting the hydrate morphology. The measurements performed on scales indicate that calcium carbonate scales strengthen the adhesion strength because of the decrease in the water wetting angle. In addition, honeycomb holes on the surface reduce amplification. Furthermore, settling quartz sand on the wall reduced the adhesion strengths by decreasing the effective sintering area of the hydrate on the underlying base. Finer sand and higher concentrations led to lower strengths. On the basis of the verified linear correlation between the hydrate adhesion strength and the adhesion work of droplets on different substrates and the influence of water conversion during deposition, both an equation and a key constant parameter were obtained to predict the sintered hydrate deposit adhesion strengths on substrates.

Molecular Ligand-Mediated Assembly of Multicomponent Nanosheet Superlattices for Compact Capacitive Energy Storage.

Inspired by the self-assembly of nanoparticle superlattices, we report a general method that exploits long-chain molecular ligands to induce ordered assembly of colloidal nanosheets (NSs), resulting in 2D laminate superlattices with high packing density. Co-assembly of two types of NSs further enables 2D/2D heterostructured superlattices. As a proof of concept, co-assembly of Ti3 C2 Tx and graphene oxide (GO) NSs followed by thermal annealing leads to MXene-rGO superlattices with tunable microstructures, which exhibit significantly higher capacitance than their filtrated counterparts, delivering an ultrahigh volumetric capacitance of 1443 F cm-3 at 2 mV s-1 . Moreover, the as-fabricated binder-free symmetric supercapacitors show a high volumetric energy density of 42.1 Wh L-1 , which is among the best reported for MXene-based materials in aqueous electrolytes. This work paves the way toward rational design of 2D material-based superstructures for energy applications.

Investigating Permeation Behavior of Flufenamic Acid Cocrystals Using a Dissolution and Permeation System.

The dissolution and permeation of the cocrystals, flufenamic acid-nicotinamide (FFA-NIC) and flufenamic acid-theophylline (FFA-TP), have been investigated in the presence of two polymers, polyvinylpyrrolidone (PVP) and copolymer of vinylpyrrolidone/vinyl acetate (PVP-VA), using a dissolution/permeation (D/P) system. It showed that the types and concentrations of the polymers and their interactions with the coformers had significant effects on the dissolution and permeation of the FFA cocrystals. The role of PVP as a stabilizing agent was not altered in spite of its interaction with the coformer of NIC or TP, which was supported by the proportional flux rate of FFA to the dissolution performance parameter (DPP). With an appropriate PVP concentration, the maximal flux rate of FFA could be obtained for a given FFA cocrystal. The situation was complicated in the presence of PVP-VA. The role of PVP-VA could change because of its association with the coformers, i.e., from a stabilizing agent to a solubilization agent. In addition, PVP-VA reduced the flux rate of FFA, in contrast to its DPP for FFA cocrystals. Finally, 1H NMR provided evidence regarding the molecular interactions between FFA, coformers, and polymers at the atomic level and gave insight into the mechanism underlying the supersaturated solution and subsequent permeation behavior of the cocrystals.

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution.

Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinylpyrrolidone/vinyl acetate (PVP-VA), on the dissolution behavior of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analyzed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and nonsink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by predissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility, and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

Temporal pulse precisely sculpted millijoule-level fiber laser injection system for high-power laser driver.

A fiber laser injection system used as a seeder for a high-power laser facility of inertial confinement fusion was designed to meet stringent requirements. Herein, we demonstrate the fiber laser injection system, whose output single-pulse energy reaches the millijoule class. With two-stage amplitude modulators, the system produces a pulse with a higher pulse shaping capability. In addition, amplifying the pulse with large-mode-area fiber and single polarization, large-mode-area photonic crystal fiber (PCF) ensures a good beam quality output. In this proof-of-principle experiment, the long-term stability of FM-to-AM modulation and pulse energy is demonstrated. The successful demonstration of this laser injection system holds great significance for future high-power laser drivers.

Investigating the Influence of Polymers on Supersaturated Flufenamic Acid Cocrystal Solutions.

The development of enabling formulations is a key stage when demonstrating the effectiveness of pharmaceutical cocrystals to maximize the oral bioavailability for poorly water soluble drugs. Inhibition of drug crystallization from a supersaturated cocrystal solution through a fundamental understanding of the nucleation and crystal growth is important. In this study, the influence of the three polymers of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2-pyrrodidone (60%) and vinyl acetate (40%) (PVP-VA) on the flufenamic acid (FFA) crystallization from three different supersaturated solutions of the pure FFA and two cocrystals of FFA-NIC CO and FFA-TP CO has been investigated by measuring nucleation induction times and desupersaturation rates in the presence and absence of seed crystals. It was found that the competition of intermolecular hydrogen bonding among drug/coformer, drug/polymer, and coformer/polymer was a key factor responsible for maintaining supersaturation through nucleation inhibition and crystal growth modification in a cocrystal solution. The supersaturated cocrystal solutions with predissolved PEG demonstrated more effective stabilization in comparison to the pure FFA in the presence of the same polymer. In contrast, neither of the two cocrystal solutions, in the presence of PVP or PVP-VA, exhibited a better performance than the pure FFA with the same predissolved polymer. The study suggests that the selection of a polymeric excipient in a cocrystal formulation should not be solely dependent on the interplay of the parent drug and polymer without considering the coformer effects.

Counteranion-Stabilized Titanium(IV) Isopolyoxocationic Clusters Isolated from Water.

A novel titanium(IV) oxo cluster comprised solely of Ti, O, and H atoms, [Ti6(Oµ)8(OtH2)20](8+) (Ti6) was synthesized in high yield via controlled hydrolysis and condensation of TiX4 (X = Cl, Br) in the presence of TBAX (TBA = tetrabutylammonium; X = Cl, Br) from water, while reactions of TiI4 and TBAI yielded [Ti8O12(OH2)24](8+) (Ti8). The structures and compositions of the clusters were determined by single-crystal X-ray crystallography, powder X-ray diffraction, inductively coupled plasma atomic emission spectrometry, and energy-dispersive spectrometry. Ti6 is comprised of six-coordinated titanium(IV) atoms bridged with µ2-O atoms, structurally similar to a typical Lindqvist polyoxometalate. On the basis of a structural comparison of Ti6 and Ti8, density functional theory calculations, and spectroscopic analysis, it is evident that both clusters are stabilized by halide counteranions via the formation of hydrogen bonds. This study not only presents the second example of a titanium(IV) isopolyoxocationic cluster isolated from water but also suggests that counteranions are generally important for synthesizing molecular fragments of titanium oxides.

Direct measurements of the interactions between clathrate hydrate particles and water droplets.

Clathrate hydrate particle agglomeration is often considered to be one of the key limiting factors in plug formation. The hydrate particle-water interaction can play a critical role in describing hydrate agglomeration, yet is severely underexplored. Therefore, this work investigates the interactions between water droplets and cyclopentane hydrate particles using a micromechanical force (MMF) apparatus. Specifically, the effect of contact time, temperature/subcooling, contact area, and the addition of Sorbitane monooleate (Span 80) surfactant on the water droplet-hydrate particle interaction behavior are studied. The measurements indicate that hydrate formation during the measurement would increase the water-hydrate interaction force significantly. The results also indicate that the contact time, subcooling and concentration of cyclopentane, which determine the hydrate formation rate and hydrate amount, will affect the hydrate-water interaction force. In addition, the interaction forces also increase with the water-hydrate contact area. The addition of Span 80 surfactant induces a change in the hydrate morphology and renders the interfaces stable versus unstable (leading to coalescence), and the contact force can affect the hydrate-water interaction behavior significantly. Compared with the hydrate-hydrate cohesion force (measured in cyclopentane), the hydrate-water adhesion force is an order of magnitude larger. These new measurements can help to provide new and critical insights into the hydrate agglomeration process and potential strategies to control this process.

Investigation of the effect of hydroxypropyl methylcellulose on the phase transformation and release profiles of carbamazepine-nicotinamide cocrystal.

PURPOSE: The aim of this work was to investigate the influence of hydroxypropyl methylcellulose (HPMC) on the phase transformation and release profile of carbamazepine-nicotinamide (CBZ-NIC) cocrystal in solution and in sustained release matrix tablets. METHODS: The polymorphic transitions of the CBZ-NIC cocrystal and its crystalline properties were examined by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman spectroscopy, and scanning electron microscopy (SEM). RESULTS: The apparent CBZ solubility and dissolution rate of CBZ-NIC cocrystal were constant in different concentrations of HPMC solutions. In a lower percentage of HPMC in the matrix tablets, the CBZ release profile of the CBZ-NIC cocrystal was nonlinear and declined over time. With an increased HPMC content in the tablets, the CBZ-NIC cocrystal formulation showed a significantly higher CBZ release rate in comparison with the other two formulations of CBZ III and the physical mixture. CONCLUSIONS: Because of a significantly improved dissolution rate of the CBZ-NIC cocrystal, the rate of CBZ entering into solution is significantly faster than the rate of formation of the CBZ-HPMC soluble complex in solution, leading to a higher supersaturation level of CBZ and subsequently precipitation of CBZ dihydrate.

Prediction of the wall factor of arbitrary particle settling through various fluid media in a cylindrical tube using artificial intelligence.

Considering the influence of particle shape and the rheological properties of fluid, two artificial intelligence methods (Artificial Neural Network and Support Vector Machine) were used to predict the wall factor which is widely introduced to deduce the net hydrodynamic drag force of confining boundaries on settling particles. 513 data points were culled from the experimental data of previous studies, which were divided into training set and test set. Particles with various shapes were divided into three kinds: sphere, cylinder, and rectangular prism; feature parameters of each kind of particle were extracted; prediction models of sphere and cylinder using artificial neural network were established. Due to the little number of rectangular prism sample, support vector machine was used to predict the wall factor, which is more suitable for addressing the problem of small samples. The characteristic dimension was presented to describe the shape and size of the diverse particles and a comprehensive prediction model of particles with arbitrary shapes was established to cover all types of conditions. Comparisons were conducted between the predicted values and the experimental results.