Differential Scanning Calorimetry Peak Research Articles

The baicalein amorphous solid dispersion to enhance the dissolution and bioavailability and effects on growth performance, meat quality, antioxidant capacity and intestinal flora in Taihang chickens

Baicalein (BAI) is a natural flavonoid with antioxidant, antitumor and antibacterial properties. However, the bioavailability of BAI was limited due to low solubility. This study aims to improve the solubility of BAI through the amorphous solid dispersion (ASD) and evaluate changes in its pharmacokinetics and pharmacodynamics in Taihang chickens. Polyethylene caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus) was chosen as the carrier, and ASD was prepared by rotary evaporation and was characterized by powder X-ray diffractions (PXRD), differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FT-IR). In vitro dissolution assays were used to screen the optimal ratio of drug to carrier, in vivo pharmacokinetic assays were conducted to investigate the promoting effect on the absorption. In addition, the effects of ASD on the growth performance, meat quality, antioxidant capacity and intestinal flora were investigated. ASD (1:9 and 2:8) did not exhibit crystal diffraction peaks of BAI in PXRD or endothermic peaks in DSC, indicating the successful preparation of ASD. The results of in vitro dissolution assay showed that the cumulative dissolution rate of ASD (2:8) within 600 min was 52.67%, which was 7.84-fold higher than BAI. The pharmacokinetic results showed that the peak concentration (Cmax) and the area under the drug-time curve (AUC0∼24) of ASD (2:8) was (5.20 ± 0.82) μg/mL and (17.03 ± 0.67) μg·h/mL, which was 1.91 and 2.64-fold higher than BAI, respectively. Dietary supplementation of BAI and ASD could increase average daily gain (ADG), while decrease feed conversion ratio (FCR), but there was no significant difference (P > 0.05). The drip loss of BAIASD group was lower than BAI group (P < 0.05). In addition, the antioxidant capacity of Taihang chickens were enhanced, the diversity and the abundance of beneficial bacteria was improved. Results of BAI upon the dietary supplementation tested in Taihang chickens, after preparation of ASD, indicating a superior enhancement effect in growth performance, meat quality, antioxidant capacity and intestinal flora due to an improved solubility and optimized bioavailability.

Quantification of crystallinity during indomethacin crystalline transformation from α- to γ-polymorphic forms and of the thermodynamic contribution to dissolution in aqueous buffer and solutions of solubilizer.

The thermodynamic properties and dissolution of indomethacin (INM) were analyzed as models for poorly water-soluble drugs. Physical mixtures of the most stable γ-form and metastable α-form of INM at various proportions were prepared, and their individual signal intensities proportional to their mole fractions were observed using X-ray powder diffraction and Fourier transform infrared spectrometry at standard temperature. The endothermic signals of the α-form, with a melting point of 426 K, and that of the γ-form, with a melting point of 433 K, were obtained by differential scanning calorimetry (DSC). Furthermore, an exothermic DSC peak of the α/γ-phase transition at approximately 428 K was obtained. As we computed the melting entropy of the α-form and that of its transformation, the frequency of the transition was quantitatively determined, which indicated the maximum of the α/γ-phase transition at an α-form proportion of 68%. Subsequently, the thermodynamic contributions of the α- and γ-forms were analyzed using a Van't Hoff plot for solubility in aqueous solutions at pH 6.8. The dissolution enthalpies for α- and γ-forms were 28.2 and 31.2 kJ mol-1, respectively, which are in agreement with the quantitative contribution predicted by the product of the temperature and melting entropy. The contribution of melting entropy was conserved in different dissolution processes with aqueous solvents containing lidocaine, diltiazem, l-carnosine, and aspartame as solubilizers; their γ-form Setschenow coefficients were -39.6, +82.9, -17.3, and +23.2, whereas those of the α-form were -39.7, +80.4, -16.7, and +22.7, respectively. We conclude that the dissolution ability of the solid state and solubilizers indicate their additivity independently.

Deconvolution of DSC peaks of high-temperature phases in an illite/smectite–CaCO3 mixture

Heat flow curves measured in differential scanning calorimetry (DSC) may contain overlapping peaks corresponding to multiple-step processes. To analyze the individual steps in such a process, a deconvolution of the overlapping peaks into the individual peaks is necessary. Using the Frazer-Suzuki function to describe asymmetric peaks, we apply a nonlinear least squares analysis to perform the decomposition of heat flow curves measured for a mixture of an illite/smectite clay with 19.6 wt.% of CaCO3. The curves contain two overlapping peaks associated with the crystallizations of gehlenite and anorthite in the temperature interval from 900 °C to 1050 °C. Several versions of the decomposition analysis may be used, depending on the number of optimized parameters. These may range from four to all eight parameters (four for either peak). We applied the versions with seven and eight fitting parameters, yielding results that are in very good agreement with the experimental data.

Amorphous solid dispersion preparation via coprecipitation improves the dissolution, oral bioavailability, and intestinal health enhancement properties of magnolol

Magnolol (MAG) is a multifunctional plant polyphenol with anti-inflammatory, antibacterial, antioxidant and antitumor properties. In poultry, it has been shown to improve growth performance, antioxidant, immune functions and intestinal health. However, its applications are limited by poor solubility and low oral bioavailability. This study aimed at improving the water solubility of MAG through solid dispersion and investigating its effects in Arbor Acre (AA) broilers. Hydroxypropyl methylcellulose succinic acid (HPMCAS) was used as a carrier to prepare magnolol solid dispersions (MAG-HPMCAS SD) via antisolvent coprecipitation, which were characterized thereafter. Optimal formulation proportions for SD were screened by in vitro dissolution assays, while its effects on improving absorption were investigated via in vivo pharmacokinetic assays. In addition, we evaluated the effects of MAG-HPMCAS SD on growth performance, antioxidant status, and gut microbiota in AA broilers. The powder samples prepared via antisolvent coprecipitation did not exhibit a crystal diffraction peak of MAG in powder X-ray diffractions or melting point peak in differential scanning calorimetry, proving the successful preparation of an amorphous solid dispersion system. The in vitro dissolution assay showed that the cumulative dissolution rate of MAG-HPMCAS(LF) SD (2:8, w/w) was 100%. Pharmacokinetic analyses revealed that the peak concentration (Cmax) of MAG-HPMCAS SD was 5.07 ± 0.73 μg/mL, which was 1.76 times greater than that of MAG. In addition, AUC0-48 and t1/2 of MAG-HPMCAS SD were 40.49 ± 6.29 g·h/mL and 9.15 ± 3.23 h, respectively, which were 2.17 and 2.56 times higher than those of MAG. Supplementation of MAG-HPMCAS SD in AA broilers significantly increased ADG (7-14 d and 15-21 d) and reduced feed conversion ratio (15-21 d) (P < 0.05). Bacterial diversity in the MAG-HPMCAS SD-supplemented group was greater than in the Control and MAG-supplemented group. Supplementation of MAG-HPMCAS SD stimulated the proliferation of beneficial bacteria, such as Lactobacillaceae and Bifidobacteriaceae. In conclusion, the MAG-HPMCAS SD prepared by coprecipitation improved the dissolution rate, the bioavailability of MAG, growth promotion, antioxidant effects and gut health in broilers.

Thermal Stability of NASICON-Type Na3V2(PO4)3 and Na4VMn(PO4)3 as Cathode Materials for Sodium-ion Batteries

The thermal stability of NASICON-type cathode materials for sodium-ion batteries was studied using differential scanning calorimetry (DSC) and in situ high-temperature powder X-ray diffraction (HTPXRD) applied to the electrodes in a pristine or charged state. Na3V2(PO4)3 and Na4VMn(PO4)3 were analyzed for their peak temperatures and the exothermic effect values of their decomposition processes, as well as the phase transformations that took place upon heating. The obtained results indicate that Mn-substituted cathode material demonstrates much poorer thermal stability in the charged state, although pristine samples of both materials exhibit similar thermal behavior without any DSC peaks or temperature-induced phase transitions in the studied temperature range. The in situ HTPXRD revealed the amorphization of desodiated Na4VMn(PO4)3-based electrodes occurring at 150~250 °C.

Networking Skills: The Effect of Graphene on the Crosslinking of Natural Rubber Nanocomposites with Sulfur and Peroxide Systems.

Tailored crosslinking in elastomers is crucial for their technical applications. The incorporation of nanoparticles with high surface-to-volume ratios not only leads to the formation of physical networks and influences the ultimate performance of nanocomposites, but it also affects the chemical crosslinking reactions. The influence of few-layer graphene (FLG) on the crosslinking behavior of natural rubber is investigated. Four different curing systems, two sulfur-based with different accelerator-to-sulfur ratios, and two peroxide-based with different peroxide concentrations, are combined with different FLG contents. Using differential scanning calorimetry (DSC), vulcametry (MDR) and swelling measurements, the results show an accelerating effect of FLG on the kinetics of the sulfur-based curing systems, with an exothermic reaction peak in DSC shifted to lower temperatures and lower scorch and curing times in the MDR. While a higher accelerator-to-sulfur ratio in combination with FLG leads to reduced crosslinking densities, the peroxide crosslinkers are hardly affected by the presence of FLG. The good agreement of crosslink densities obtained from the swelling behavior confirms the suitability of vulcameter measurements for monitoring the complex vulcanization process of such nanocomposite systems in a simple and efficient way. The reinforcing effect of FLG shows the highest relative improvements in weakly crosslinked nanocomposites.

Effect of annealing on thermal and dynamic mechanical properties of poly(lactic acid)

AbstractEffects of annealing temperature (Ta: 80–140°C) and time (ta: 3‐30 h) on the crystalline phase transition in poly(lactic acid) (PLA) were studied by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). In the DSC curves, the sample annealed at Ta = 80°C with time interval (ta: 10–30 h) demonstrates a peculiarly small exothermal peak (Texo) around 130°C, just prior to the melting point, corresponding to the disorder‐to‐order (α’‐to‐α) phase transition, while the sample annealed at temperature (Ta: 90–110°C) shows a double melting behavior considered as the α’‐α phase transition. Towards low temperatures, the glass modulus Eg reported by DMA thermograms, shows an important increase (~30,000 MPa) at Ta = 80°C for ta = 3 h, due to the extremely high self‐nucleation density in low‐crystallized PLA materials. After a sharp drop to 3600 MPa at Ta = 110°C, a marked improvement of Eg (15,900 MPa) is observed around Ta = 120°C for all samples, regardless of time ta. This interesting effect (improvement of Eg in the range Ta = 100–120°C) can be correlated with the grow of crystallinity in the same domain of Ta, and the α’‐α phase transition Ta (Ta: 90–110°C) determined by the double Tm melting DSC peak, which is confirmed by the increase of Tg for Ta = 90–110°C.

Impact of Ni on the thermophysical and thermodynamic properties of Fe–C–Ni based alloys

Three model alloys based on Fe-C-Ni were studied containing carbon between 0.338 and 0.382 wt. % and nickel between 1.084 and 4.478 wt. %. Phase transition temperatures, heat capacity, enthalpy change, heat of fusion, coefficient of thermal expansion, and density were experimentally and theoretically determined in the high-temperature area from 1000 °C to 1595 °C. A number of techniques, namely differential thermal analysis (DTA), differential scanning calorimetry (DSC), and dilatometry, were used in this study, and the heat of fusion was determined by two approaches, that is, from the DSC peak area and from the enthalpy change. The experimental data were compared and discussed with the calculation results obtained using SW IDS, JMatPro, and Thermo-Calc operating with the commercially available TCFE8 thermodynamic database. The obtained experimental results show that the liquidus temperature and the coefficient of thermal expansion decrease with increasing nickel content. On the contrary, the density and heat of fusion values derived from the DSC peak increase with increasing nickel content. Furthermore, an ambiguous influence of nickel on the change in solidus temperature, heat capacity, enthalpy change, and heat of fusion obtained from the enthalpy change was observed.

Modeling the Thermal Denaturation of the Protein-Water System in Pulses (Lentils, Beans, and Chickpeas).

Thermal treatment applied during the cooking of pulses leads to denaturation and even aggregation of the proteins, which may impact protein digestibility. Thermal transitions of lentil, chickpea, and bean proteins were studied using differential scanning calorimetry (DSC). Protein-enriched samples were obtained by dry air classification of dehulled seeds and were heated to 160 °C, with water contents ranging from 0.2 to 4 kg/kg on a dry basis. The DSC peaks of the resulting endotherms were successfully modeled as overlapping Gaussian functions. The denaturation temperatures were modeled as a function of the temperature according to the Flory-Huggins theory. The modeling allows for the calculation of the degree of protein transition for any temperature and moisture condition. The denaturation diagrams reflect the different protein compositions of lentil, chickpea, and bean (particularly the 11S/7S globulin ratio). Chickpea proteins were more thermally stable than those from lentil and bean. Proteins underwent an irreversible transition, suggesting that unfolding and aggregation were coupled.

Precipitation in lean Mg–Zn–Ca alloys

While lean Mg–Zn–Ca alloys are promising materials for temporary implants, questions remain on the impact of Zn and Ca on the microstructure. In this context, the precipitation of Zn and Ca in Mg-1.5Zn-0.25Ca (in wt.%), initially extruded at 330°C, towards Mg–Ca binary precipitates or Ca–Mg–Zn ternary precipitates was probed in a multiscale correlative approach using atom probe tomography (APT) and analytical transmission electron microscopy (TEM). Particular focus was set on the ternary precipitate phase whose structure is debated. In the as-extruded material, the binary precipitates are made of hexagonal C14 Mg2Ca containing up to about 3 at.% of Zn. The ternary ones are based on the hexagonal Ca2Mg5Zn5 prototype structure with a composition close to Ca3Mg11Zn4, as deduced from atomically resolved EDS mapping and scanning TEM imaging, supported by simulations. The precipitation sequence was scrutinized upon linear heating from room temperature to 375°C, starting from the solutionized material. Three exothermic differential scanning calorimetry (DSC) peaks were observed, at respectively 125, 250 and 320°C. Samples were taken after the peak decays, at respectively 205, 260 and 375°C for structural analysis. At 205°C, APT analysis revealed Ca-rich, Zn-rich and Zn‒Ca-rich clusters of about 3 nm in size and with a number density of 5.7 × 1023 m−3. At 260°C, APT and TEM showed mono-layered Zn‒Ca-rich Guinier‒Preston (GP) zones of about 8 nm in size and with a number density of 1.3 × 1023 m−3. At 375°C, larger and highly coherent elongated precipitates were found, with a size of about 50 nm. They occur as binary Mg–Ca precipitates or ternary Ca2Mg6Zn3 precipitates, as deduced from scanning TEM-based energy dispersive X-ray spectroscopy (EDS) and nanodiffraction in TEM. Here, the binary precipitates outnumber the ternary ones, while in the as-extruded material the ternary precipitates outnumber the binary ones, which corresponds well to the calculated phase diagram. We correlated the microstructure to hardness probed by Vickers testing. The largest hardening relates to the end of the 125°C DSC peak and thus to GP zones, which outperform the hardening induced by the nanometer-sized clusters and the larger intermetallic particles. The complexity of the precipitation sequence in lean Mg–Zn–Ca alloys is discussed.

Copper Oxide Nano‐Catalyst Incorporated TEGDN/NC/DAG Propellants: Thermal Behaviors and Kinetics

AbstractThe copper oxide nanoparticles (nano‐CuO)/nitrocellulose (NC)/triethyleneglycol dinitrate (TEGDN)/diaminoglyoxime (DAG) nanocomposites were successfully prepared as a convenient propellants. The catalytic effect of nano‐CuO on the thermal behavior and the decomposition kinetics of the samples were precisely verified via thermogravimetry (TGA) and differential scanning calorimetry (DSC). The CuO nanoparticles significantly altered the thermal pattern of the studied energetic materials, e. g., the temperatures corresponded to the DSC peaks were changed by increasing the nano‐CuO amount. Moreover, the catalyst resulted in the decrement in the activation energy of the decomposition stage by ∼30–50 kJ mol−1 and also improved the thermal stability of TEGDN/NC/DAG composite. The thermokinetic and thermodynamic parameters of the energetic nanocomposites were explained by using the Kissinger and Starink differential methods and the integral methods of Coats Redfern and Flynn‐Wall‐Ozawa. The mechanism function and the kinetic equation of the main exothermal decomposition step for the parent composite was found to be different from that of the 1–3 % CuO‐contained nanocomposites.

In vitro and in vivo activity of thermosensitive liposomes loaded with doxorubicin and cisplatin

Thermosensitive liposomes loaded with cisplatin and doxorubicin composed of DPPC, DSPC, and DPPE-PEG5000 with different ratios were prepared by thin film hydration method. The Differential Scanning Calorimetry (DSC) curves showed that the liposomes composed of DPPC-DSPC-DPPE-PEG5000 with phospholipid ratio 95:5:0.05 w/w were a suitable formulation as thermosensitive liposomes with a DSC peak at 42.1 °C. The effect of doxorubicin and cisplatin encapsulated non-thermosensitive and thermosensitive liposomes on cellular proliferation and IC50 in SKBR3 & MDA-MB-231 breast cancer and PC-3 & LNcaP prostate cancer cell lines was investigated. The results showed that doxorubicin loaded into thermosensitive liposomes showed 20-fold decrease in the IC50 at 42 °C while comparing it with the same at 37 °C. Also, the results showed a more than 35-fold and 12-fold decrease in the IC50 of cisplatin thermosensitive liposomes at 42 °C, while compared with free cisplatin and cisplatin thermosensitive liposomes at any temperature. The in vivo results showed that the effect of doxorubicin encapsulated thermosensitive liposomes at hyperthermic conditions during the treatment as the tumor growth inhibition was measured 1.5-fold higher than any of the liposomal formulations of doxorubicin. It was also noticed that the tumor volume reduced to 150 mm3 in doxorubicin thermosensitive liposomes (G8) after 3 weeks during the treatment, but increased to 196 mm3 after 4 weeks. The Kaplan-Meir curve showed the 100% survival of the animals from G8 (thermosensitive liposomes containing doxorubicin plus hyperthermia) after 12 weeks. The flow cytometry data revealed more than 25% apoptotic cells and 6.25% necrotic cells in the tumor cells from the tissues of the G8 group of the animals. The results clearly indicate the superior efficacy of doxorubicin and cisplatin containing thermosensitive liposomes treatment during hyperthermia.

Changes Experienced by Low-Concentration Lipid Bicelles as a Function of Temperature.

Differential scanning calorimetry (DSC) of dipalmitoyl phosphatidylcholine (DPPC), dihexanoyl phosphatidylcholine, and dipalmitoyl phosphatidylglycerol bicelles reveals two endothermic peaks. Based on analysis of small angle neutron scattering and small angle X-ray scattering data, the two DSC peaks are associated with the melting of DPPC and a change in bicellar morphology─namely, either bicelle-to-spherical vesicle or oblate-to-spherical vesicle. The reversibility of the two structural transformations was examined by DSC and found to be consistent with the corresponding small angle scattering data. However, the peak that is not associated with the melting of DPPC does not correspond to any structural transformation for bicelles containing distearoyl phosphatidylethanolamine conjugated with polyethylene glycol. Based on complementary experimental data, we conclude that membrane flexibility, lipid miscibility, and differential solubility between the long- and short-chain lipids in water are important parameters controlling the reversibility of morphologies experienced by the bicelles.

Enhancing compatibility and hydrophilicity of polysulfone/poly (ethylene-co-vinyl alcohol) copolymer blend ultrafiltration membranes using polyethylene glycol as hydrophilic additive and compatibilizer

Hydrophilic poly (ethylene-co-vinyl alcohol) (EVOH) was blended with hydrophobic polysulfone (PSF) in the presence of polyethylene glycol (PEG) (20 kDa), which acted as a hydrophilic additive and compatibilizer, to fabricate ultrafiltration (UF) membranes with high porosity and antifouling properties. The polymer blend containing 10 wt% EVOH was selected for optimization using PEG (0 to 24 wt%). After a detailed study, it was concluded that 20 wt% of PEG content was optimal for mixing with PSF/EVOH to increase miscibility. The membranes were characterized using differential scanning calorimetry (DSC) analysis, contact angle, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The effectiveness of PEG as a compatibilizer was observed via no phase separation occurred when the solution was allowed to stand at room temperature for four weeks. It was further confirmed by the appearance of a single Tm peak in DSC. In addition, molecular dynamic simulations illustrated that the PSF/EVOH 90/10 wt% blend had a radial distribution of g(r) = 3.29 Å, and g(r) = 2.69 Å in the presence of PEG, indicating better miscibility in the presence of PEG. Pure water permeance of blend membrane (85/15 wt%) reached 316 L.m-2h−1 bar−1, 54% greater than the pristine membrane. Simultaneously, bovine serum albumin (BSA) rejection of up to 97% and permeance recovery ratio of 87% were observed for the PSF/EVOH 90/10 wt% blend membrane, showing improved hydrophilicity and antifouling properties. These findings identify a potential modifier for fabricating low fouling UF membranes for wastewater treatment by blending with EVOH and PEG.

Thermal stability of nanocrystalline CoCrFeNi multi-principal element alloy: Effect of the degree of severe plastic deformation

The effect of the degree of severe plastic deformation (SPD) on the thermal stability of a nanocrystalline CoCrFeNi multi-principal element alloy was studied. The SPD method of high-pressure torsion (HPT) was utilized to achieve the nanocrystalline microstructure. The structural stability was investigated near the centers and edges of the HPT-processed disks deformed for ½, 1, 5 and 10 turns. For almost all studied samples, two exothermic peaks in the temperature ranges of 600–750 and 750–950 K were observed by differential scanning calorimetry (DSC) between room temperature and 1000 K. The saturation released heat value for the first DSC peak was about 4 J/g that was achieved at the shear strain of ∼200. For the second exothermic peak, the released heat saturated at the shear strain of about 20 with the value of about 6–7 J/g. It was revealed that the first DSC peak is related to the annihilation of dislocations for low degree of deformation. At the same time, for edge parts of the disks processed by one or higher numbers of turns the vacancy annihilation has also a major contribution to the first exothermic peak. The annihilated vacancy concentration estimated from the released heat was between (0.6–0.9) × 10−3. The second DSC peak was related to the disappearance of grain boundaries due to recrystallization and annihilation of the remaining dislocations. The HPT-processed CoCrFeNi MPEA samples exhibited very high hardness values between 4000 and 5100 MPa, depending on the number of turns and the location along the disk radius. The hardness decreased only during the second exothermic peak when recrystallization occurred.

The machine learning method for overlapping peak decompositions in differential scanning calorimetry

An overlapping peak resolving (OPR) method based on the machine learning theory is developed to identify the independent peaks constituting the overlapping peaks in differential scanning calorimetry. The content prediction model (CPM) is presented to analyze the contents of the chemical constituents by decomposing the overlapping peaks and establishing the relationship between the contents and peak areas of the substances. The model is applied respectively to some theoretically constructed and experimentally measured overlapping peaks to validate the reliability and feasibility of the proposed method. The results show that the contents of the chemical constituents can be accurately calculated by the CPM. The validations indicate that the analysis errors of the CPM show a relatively stable trend with the changes of the separation degrees and peak-height ratios. Furthermore, the computational burden of the proposed method is also less than that of the existing OPR techniques.

Quantification of Compatibility Between Polymeric Excipients and\xa0Atenolol Using Principal Component Analysis and Hierarchical\xa0Cluster Analysis

An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating–cooling–reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C.Graphical abstract

Development of Natural Polysaccharide-Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment.

The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the P-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential −14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R2 = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10−fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.

A reinforcement learning based method for protein’s differential scanning calorimetry signal separation

Differential scanning calorimetry (DSC) is a powerful technique to study protein stability, since the DSC test data provides valuable insights to characterize protein folding thermodynamics. Researchers in the drug discovery field need to manually analyze the DSC curves in multiple steps, such as baseline subtraction, data fitting, integration, and domain deconvolution. To improve the efficiency and consistency of data processing, machine learning methods for automatic DSC peak identification and baseline estimation were seen in prior research. However, the DSC’s automatic peak separation remained unexplored, despite its significant role in explaining the multi-domain protein unfolding. In this research, we propose a method based on reinforcement learning to separate the overlapping peaks of the DSC signal. We use two types of protein data to verify the effectiveness of this method. It automatically deconvolutes the peak signals into multiple sub-peaks. Our automated analysis method could lead to improved efficiency in DSC signal analysis when high volume data is involved. The code and data for this work can be found at: https://github.com/shuyu-wang/DSC_analysis_peak_separation.

Tunable Martensitic Transformation and Magnetic Properties of Sm-Doped NiMnSn Ferromagnetic Shape Memory Alloys

NiMnSn ferromagnetic shape memory alloys exhibit martensitic transformation at low temperatures, restricting their applications. Therefore, this is a key factor in improving the martensitic transformation temperature, which is effectively carried out by proper element doping. In this research, we investigated the martensitic transformation and magnetic properties of Ni43Mn46-x SmxSn11 (x = 0, 1, 2, 3) alloys on the basis of structural and magnetic measurements. X-ray diffraction showed that the crystal structure transforms from the cubic L21 to the orthorhombic martensite and gamma (γ) phases. The reverse martensitic and martensitic transformations were indicated by exothermic and endothermic peaks in differential scanning calorimetry. The martensitic transformation temperature increased considerably with Sm doping and exceeded room temperature for Sm = 3 at. %. The Ni43Mn45SmSn11 alloy exhibited magnetostructural transformation, leading to a large magnetocaloric effect near room temperature. The existence of thermal hysteresis and the metamagnetic behavior of Ni43Mn45SmSn11 confirm the first-order magnetostructural transition. The magnetic entropy change reached 20 J·kg−1·K−1 at 266 K, and the refrigeration capacity reached ~162 J·Kg−1, for Ni43Mn45SmSn11 under a magnetic field variation of 0–5 T.