Differential Scanning Calorimetry Spectra Research Articles

Effect of Dy3+ ions on physical, structural and thermal properties of ZnNaPbB glasses

In this report, inspired by the excellent spectroscopic characteristics of dysprosium (Dy3+) ions doped borate glasses, a series with the composition (70-x)B2O3-10ZnO-10PbO-10Na2CO3-xDy2O3 (here ‘x’ have the values as 0.1, 0.5, 1.0, 1.5 and 2.0 in mol % ) was made using the melt quenching process and named as ZnNaPbBDy0.1 to ZnNaPbBDy2.0. Here we study the physical, structural and thermal properties of Dy3+ ions doped Zinc Sodium Lead Borate (ZnNaPbB) glasses through different characterization techniques like Fourier transform infrared (FT-IR), Raman spectroscopy, Differential scanning calorimetry (DSC) and decay spectroscopy. Several physical parameters were evaluated to assess the effect of Dy3+ inclusion. FT-IR and Raman spectra confirm the presence of BO3 and BO4 structural units. The data recorded by DSC spectra have been used to predict the glass transition temperature (Tg). The nature of decay spectra was estimated which diverges from exponential to non-exponential at higher concentrations. The decay spectral data is used to calculate the experimental lifetimes for all the glass samples. The Inoakutti Hirayama (I-H) model and Dexter’s plot are used to confirm the type of interaction between the donor and acceptor Dy3+- Dy3+ ions is dipole–dipole in nature that is responsible for the emission intensity quenching with concentration. All the above results might be advantageous for variety of applications in photonic devices.

Production of biosurfactant by Bacillus megaterieum using agro-food wastes and its application in petroleum sludge oil recovery.

The objective of this study is to utilize cost-effective renewable substrates derived from agro-food wastes for the production of biosurfactant by Bacillus megaterium, which was isolated from petroleum sludge. Various agro-food waste materials, namely potato peelings (PP), rice cooking water (RW), biscuit by products (BB), carob pods (CP), and eggshells, were evaluated as nutrient sources for bacterial growth compared to a synthetic medium (SM). The results indicate that the medium comprising carob pods, potato peels supplemented with eggshells promoted the growth of the bacteria and the production of Biosurfactants at a rate of 150mg/l and 140mg/l respectively. The biosurfactant exhibited an emulsification index (E24) of 55.23 ± 0.32%, 46.47 ± 3% 43.80 ± 0.4%, 18.33 ± 0.25% and 20 ± 0.11% for PP, CP, SM, BB and RW respectively. The biosurfactant produced from PP had the ability to decrease the surface tension of water from 74 to 39.38 mN/m, with a critical micelle concentration (CMC) of 15mg/L. The chemical characterization of purified biosurfactant was done using Fourier-transform infrared spectroscopy (FTIR) and Thermal gravity (TG), as well as differential scanning calorimetry (DSC) analysis (TG/DSC), revealing the functional groups and thermostability of the biosurfactant. The DSC spectrum for PP biosurfactant showed the highest thermostability with crystalline temperature (Tc) of 150°C and melting point (Tm) of 295°C. The extracted biosurfactant was mixed with petroleum sludge, composed of heavy oil, 40.64 ± 0.19% of extracted oil was obtained after 5h of reaction while using PP based medium.

Development and Characterization of Quercetin-Loaded Polymeric Liposomes with Gelatin-Poly(ethylene glycol)-Folic Acid Coating to Increase Their Long-Circulating and Anticancer Activity.

Liposomes as drug-delivery systems have been researched and applied in multiple scientific reports and introduced as patented products with interesting therapeutic properties. Despite various advantages, this drug carrier faces major difficulties in its innate stability, cancer cell specificity, and control over the release of hydrophobic drugs, particularly quercetin, a naturally derived drug that carries many desirable characteristics for anticancer treatment. To improve the effectiveness of liposomes to deliver quercetin by tackling and mitigating the mentioned hurdles, we developed a strategy to establish the ability to passively target cancerous cells, as well as to increase the bioavailability of loaded drugs by incorporating poly(ethylene glycol), gelatin, and folic acid moieties to modify the liposomal system's surface. This research developed a chemically synthesized gelatin, poly(ethylene glycol), and folic acid as a single polymer to coat drug-loaded liposome systems. Liposomes were coated with gelatin-poly(ethylene glycol)-folic acid by electrostatic interaction, characterized by their size, morphology, ζ potential, drug loading efficiency, infrared structures, differential scanning calorimetry spectra, and drug-releasing profiles, and then evaluated for their cytotoxicity to MCF-7 breast cancer cells, as well as cellular uptake, analyzed by confocal imaging to further elaborate on the in vitro behavior of the coated liposome. The results indicated an unusual change in size with increased coating materials, followed by increased colloidal stability, ζ potential, and improved cytotoxicity to cancer cells, as shown by the cellular viability test with MCF-7. Cellular uptake also confirmed these results, providing data for the effects of biopolymer coating, while confirming that folic acid can increase the uptake of liposome by cancer cells. In consideration of such results, the modified gelatin-poly(ethylene glycol)-folic acid-coated liposome can be a potential system in delivering the assigned anticancer compound. This modified biopolymer showed excellent properties as a coating material and should be considered for further practical applications in the future.

Enhancing solubility and oral bioavailability of rosuvastatin through interpenetrating polymer network (IPN) nanogels: Fabrication, characterization, and in-vivo efficacy assessment

Rosuvastatin (RST) exhibits low aqueous solubility, presenting a challenge for its effective oral administration. The objective of this study is to improve the solubility of RST through the creation and assessment of interpenetrating polymer network (IPN) nanogels. The nanogels were produced via a free radical polymerization method, where hydrophilic polymers β-cyclodextrin (β-CD) and Poloxamer-407 (P407) were combined with the monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS). Comprehensive characterization of the nanogels included drug loading efficiency, solubility studies, zeta sizer measurements, sol-gel analysis, Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), swelling studies, and in-vitro release analysis. Oral toxicity experiments were performed to verify the safety of the β-CD/Poloxamer-407-co-poly (AMPS) IPN nanogels when taken by mouth. The scanning electron microscopy (SEM) investigation unveiled a network structure characterised by porosity and sponginess. The thermal stability and complex synthesis of the nanogel components were validated by the FTIR, TGA, and DSC spectra. X-ray diffraction (XRD) analysis indicated a reduction in the crystallinity of RST within the nanogel matrices. The optimized nanogels formulation demonstrated a particle size of 185.71 ± 1.03 nm. Comparative studies with a reference product highlighted significant enhancements in drug solubility and release characteristics attributed to the fabricated nanogels. Toxicity assessments confirmed the non-toxic nature of the nanogels, supporting their biocompatibility. In-vivo studies using hyperlipidemic animal models validated the anti-hyperlipidemic efficacy of the developed nanogels. The nanogels' biocompatibility, high solubilization capacity, improved dissolution profile, rapid production process, and superior physicochemical properties underscore their potential as an effective oral delivery system for lipophilic drugs.

Posaconazole-glutaric acid cocrystal tablet with improved Dissolution rate

Posaconazole is used to prevent fungal infections in patients having severely weakened immune system and has poor aqueous solubility which impairs its dissolution in upper gastric fluid producing problems in different formulations. These characteristics hinder its therapeutic application by delaying absorption rate and thereby onset of action. In the present study, an attempt was made to prepare posaconazole cocrystals with improved physicochemical properties for better therapeutic activity. Cocrystals were prepared with glutaric acid in 1:1 molar using ethanol by solvent drop grinding technique. The co-crystals formed were characterized by melting point determination, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and dissolution studies. Posaconazole-glutaric acid co-crystals were further formulated as fast disintegrating tablets. The IR study revealed the shifting of characteristic bands of posaconazole. The PXRD pattern indicated cocrystal crystallinity and a considerable difference in 2θ value of intense peaks. The variation in fusion endotherm, which is in agreement with melting point, was designated by DSC spectra of posaconazole cocrystal. A significant improvement in the dissolution rate was observed in the case of cocrystals based tablets than pure posaconazole tablets.

(Digital Presentation) Porous Silicon Formed by Electrochemical, Chemical and Combined Etching

This work is devoted the thermophysical characteristics (TPC) of PS formed by Electrochemical, Metal-assisted chemical and combined etching methods. The TPC of PS/MACE+EC formed by the MACE+EC– method is higher than those of the PS/EC and PS/MACE samples formed by the EC and MACE methods. The energy activity of water splitting on the surface of PS/MACE+EC is higher than the energy activity of the PS/EC and PS/MACE samples. The combined (MACE+EC) method is the best method for obtaining PS, which has the highest energy activity in water splitting processes. The activation energy of water splitting processes Ea(PS/MACE+EC) is higher than the energy activity of the Ea(PS/EC) and Ea(PS/MACE) samples. The presence of Ni particles in the pores of PS<Ni> stabilizes the them TPC. The TPC of PS were studied in comparison with the TPC of crystalline (c-Si) and powdered silicon (powder-Si). It is known that PS has a high catalytic activity of hydrogen evolution during photoelectrochemical splitting of water. For example, the use of a surface enriched Ni layer on the surface of a PS photocathode PS<Ni> made it possible to increase its catalytic activity two times higher than the catalytic activity of the Pt- electrode in the reaction of hydrogen evolution [1]. The TPC of PS samples formed by EC, MACE and combined (MACE+EC)- etching methods are studied in comparison with the TPC of c-Si and powder-Si samples, Table. Method Electrolyte Composition Marked I Et1 HF:H2O2=1:1 EC II Et2 HF:H2O2: Ni(NO3)2 =1:1:1 МАСЕ III Et3 HF:H2O2: Ni(NO3)2 =1:1:1 EC+МАСЕ According of electron microscopy research the highest porosity is observed on the PS/MACE+EC samples, the smallest - on the PS/MACE sample formed by the MACE- method. The Raman spectra testify this, PS/MACE+EC(Et3) samples have a higher intensity of the Raman peak at a high-frequency shift due to electron-phonon scattering, the intensity and frequency of which depend on the concentration of scattering centers and, consequently, on the conditions for the formation of pores [2]. The TPC of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) spectra record changes in the mass Δm of the sample and heat flux ΔQ with an isobaric temperature change ΔT at the points of T-characteristic. An analysis of the calorimetric TPC and the TGA and DSC spectra shows that c-Si and powder have almost the same patterns of change in thermal conductivity, in contrast to the PS-spectra. The PS/EC, PS/MACE samples have the maximum change in heat flux Q(PS/EC)=187.6 mW, Q(PS/MACE)=231.6 mW, in contrast to powder-Si Q(powder-Si)=107.1 mW and c-Si ΔQ(c-Si)=65.02 mW. This dependence, which is responsible for the heat flux ΔQ change in the high T-range is associated with the maximum developed surface PS. Due to the fact that the presence of the Ni in the pores of PS<Ni>/MACE and PS<Ni>/MACE+EC stabilizes the TPC of PS, and thereby prevents significant changes in the TPC of Ni-containing PS<Ni>, in contrast to PS that does not Ni-contain in pores. Also have carried out experiments on the evaporation of water droplets at room temperature from the surface of c-Si and PS/EC, PS/MACE PS/MACE+EC samples. Experiments on the evaporation of water droplets at Troom from the surface of crystalline and PS samples obtained by various etching methods showed that the highest energy activity is observed in PS/MACE+EC samples, Ea(PS/MACE+EC) = 0.2087 eV, which is much higher than Ea(PS/EC) = 0.070 eV, Ea(PS/MACE) = 0.050 eV and Еа(c-Si) = 0.025 eV,The porous surface of the PS/MACE+EC sample has the highest energy activity compared to the PS/EC and PS/MACE samples, which is due to the high porosity of PS/MACE+EC. The PS/MACE and PS/MACE+EC samples showed high energy stability over 1 year in water evaporation experiments. The values of the heat capacities of various EC-, MACE-, EC+MACE - etching methods are established: - Cp(c -Si) = 20.7 KJ/gK, Cp(powder-Si) = 13.11 KJ/gK, Cp(PS/MACE) = 12.79 KJ/gK, Cp(PS/AE) = 5.62 KJ/gK.Combination of electrochemical etching with Ni-stimulated and chemical etching (EC+MACE) makes the possibility Ni-containing nanoporous silicon with high energy activity in water splitting processes: - Еа(PS/MACE+EC) = 0.2087 eV, Еа(PS/MACE) = 0.070 eV , Еа(PS/АЕ) =0.050 eV.The Ni- presence in the pores stabilizes the TPC of PS/MACE and PS/MACE+EC. The stability of Ni-containing samples PS/MACE+EC) and Ea(PS/MACE) is maintained for one year. [1] K.B. Tynyshtykbayev et al. Russian Microelectronics, 2016, Vol. 45, Nos. 8–9, pp. 603–612. https://doi.org/10.1134/S106373971608014X[2] K. Tynyshtykbayev et al. ECS Journal of Solid State Science and Technology, 2021 10 013009 DOI: 10.1149/2162-8777/abdd86

Solution blow co-spinning of cellulose acetate with poly(ethylene oxide). Structure, morphology, and properties of nanofibers

Cellulose acetate (CA) nanofibers are prepared using solution blow co-spinning (SBS) with poly(ethylene oxide) (PEO). The pure CA membranes are obtained by washing water-soluble PEO from the fibrous CA-PEO blend. Nanofibrous membranes are characterized using optical and scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared spectroscopy (ATR-FTIR), and surface zeta potential measurements. Thermal transitions from DSC and ATR-FTIR spectra analysis were used to confirm the removal of the PEO. Although the characteristic signals of PEO are not observed by FTIR, an additional thermal step transition in CA nanofibers indicates the embedding of a small amount of PEO (up to 6 wt%). SEM analysis shows that CA-PEO blends are constituted by fibers with mean diameters from 671 to 857 nm (depending on the SBS parameters), while after PEO removal, diameters range from 567 to 605 nm. We propose a new method for staining CA-PEO membranes with iodine solution in absolute ethanol that allows the differentiation of CA and PEO components with an optical microscope. The microscopy results suggest that PEO assists in the spinning by enveloping CA nanofibers, allowing uninterrupted processing. The successful deacetylation to cellulose using an aqueous KOH solution is confirmed with zeta potential measurements and ATR-FTIR.

Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study.

Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90-95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box-Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of -34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer-Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm2) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (p &lt; 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP.

Co-crystals of ezetimibe: design, formulation and evaluation

Crystallization is a very promising approach to design solid-state properties with desired physicochemical properties. The objective of the present research work was to design, formulate and evaluate Ezetimibe cocrystals. In the present study, Cocrystals of Biopharmaceutics Classification System (BCS) Class II drug, Ezetimibe using 3-pyridine carboxamide as coformer were prepared. 3-pyridine carboxamide was selected as suitable coformer from initial screening. Cocrystals of Ezetimibe with 3-pyridine carboxamide were obtained in 1:1 ratio by solution crystallization method. Hot stage microscopy indicated interaction among drug and coformer. Differential scanning calorimetry spectra of formulated cocrystals reflected shift in endotherm corresponding to melting point in comparison to Ezetimibe, coformer and physical mixture. Fourier transform infrared (FTIR) spectra indicated towards shifting in specific bands characteristic of Ezetimibe. X-Ray Powder Diffraction pattern pointed towards crystallinity and difference in 2θ values of characteristic peaks. The cocrystals showed faster dissolution rate in comparison to Ezetimibe and marketed sample. Pharmacodynamic investigation reveals that cocrystals reduced lipid levels in serum in comparison to pure drug. Pharmaceutical Cocrystals of Ezetimibe with 3-pyridine carboxamide represented a promising approach to improve bioavailability of Ezetimibe drug.

Ultrasound assisted slightly acidic electrolyzed water treatment on the protein structure stability of vacuum‐packaged sea bass (Lateolabrax japonicas) during refrigerated storage

AbstractThis study evaluated the synergistic effects of ultrasound (US) and slightly acidic electrolyzed water (SAEW) treatment on the myofibril protein structure of vacuum‐packed sea bass (Lateolabrax japonicas) during refrigerated storage. Fresh sea bass fillets were treated with US, SAEW, US combined with SAEW treatment (US + SAEW), and sterile water (Control) for 10 min, respectively. Different indexes, such as hardness, myofibril fragmentation index (MFI), water activity (aw), and surface hydrophobicity, which also combined with protein characteristic (intrinsic fluorescence intensity) were analyzed. The results showed that the US treatment increased the MFI and surface hydrophobicity of sea bass. Compared with the control group, the bactericidal effect of US + SAEW treatment made the sample better water holding capacity, water activity, and higher fluorescence intensity. Differential scanning calorimetry spectrum results showed that samples treated by US had loose myofibrillary structure, which was convenient for SAEW to act more effectively. US + SAEW treatment retarded the degradation of protein. These results provided evidence that US + SAEW treatment could maintain the quality of fish.

Chitosan-ethyl cellulose microspheres of domperidone for nasal delivery: Preparation, in-vitro characterization, in-vivo study for pharmacokinetic evaluation and bioavailability enhancement

The strategies to avoid the first-pass metabolism via nose to systemic pathway are been explored to improve the bioavailability of the therapeutic agents. The present study aimed to formulate and evaluate the chitosan (CH)-ethylcellulose (EC) based microspheres for the systemic delivery of domperidone (DOM) via the nasal route to improve its bioavailability which is poor (18%) owing to the extensive first-pass metabolism. The microspheres were prepared by the solvent evaporation method and evaluated for certain in-vitro and in-vivo parameters. In-vivo study for optimized DOM-Microsphs (F1) formulation was performed on Wistar rats for the evaluation of bioavailability and pharmacokinetic parameters after nasal administration and compared to nasally administered DOM solution (DOM-Sol), and orally administered DOM-Sol & commercially available tablet formulation (Com-Tab). In-vitro results of optimized formulation (F1) demonstrated that the microspheres were spherical with 21.12 ± 0.51 μm particle size, 84.79 ± 1.39% entrapment efficiency, 50.68 ± 0.96% drug loading, 81.2 ± 6.75% drug release in 8 h. DOM loaded microspheres demonstrated 2 fold ex-vivo permeation than that Com-Tab. X-ray diffraction and differential scanning calorimetry spectra do not display the characteristic peak of DOM, thus recommending the encapsulation of the drug in the polymeric core. The relative bioavailability of optimized formulation administered nasally in comparison to DOM-Sol administered orally, DOM Com-Tab administered orally, and DOM-Sol administered nasally was found to be 3.75, 2.61, and 1.77 folds respectively indicating the superiority of developed formulation. The developed microspheres were found to be promising for the bioavailability enhancement of DOM through the nasal route by avoiding its first-pass metabolism. Therefore, the development of microspheres for nasal to systemic route might better choice and a finer option for DOM bioavailability enhancement as well as for avoiding the problem associated with the drug due to irregular drug concentration in the blood with oral administration of the conventional formulation.

Characterisation of Fat Crystal Polymorphism in Cocoa Butter by Time-Domain NMR and DSC Deconvolution.

The polymorphic state of edible fats is an important quality parameter in fat research as well as in industrial applications. Nowadays, X-ray diffraction (XRD) is the most commonly used method to determine the polymorphic state. However, quantification of the different polymorphic forms present in a sample is not straightforward. Differential Scanning Calorimetry (DSC) is another method which provides information about fat crystallization processes: the different peaks in the DSC spectrum can be coupled to the melting/crystallisation of certain polymorphs. During the last decade, nuclear magnetic resonance (NMR) has been proposed as a method to determine, qualitatively and/or quantitatively, the polymorphic forms present in fat samples. In this work, DSC- and NMR-deconvolution methods were evaluated on their ability to determine the polymorphic state of cocoa butter, with XRD as a reference method. Cocoa butter was subjected to two different temperature profiles, which enforced cocoa butter crystallization in different polymorphic forms. It was found that XRD remains the best method to qualitatively determine the polymorphic state of the fat. Whereas the quantitative NMR and DSC deconvolution results were not fully in line with the XRD results in all cases, NMR deconvolution showed great promise both in a qualitative and quantitative way.

Tomato Oil Encapsulation by α-, β-, and γ-Cyclodextrins: A Comparative Study on the Formation of Supramolecular Structures, Antioxidant Activity, and Carotenoid Stability.

Cyclodextrins (CDs) are oligosaccharides, comprising 6 (α), 7 (β), or 8 (γ) glucose residues, used to prepare oil-in-water emulsions and improve oil stability towards degradation. In this research, the aptitude of α-, β-, and γ-CDs to form complexes with a supercritical CO2 extracted lycopene-rich tomato oil (TO) was comparatively assessed. TO/CD emulsions and the resulting freeze-dried powders were characterized by microscopy, Fourier transform infrared-attenuated total reflection (FTIR-ATR), and differential scanning calorimetry (DSC), as well as for their antioxidant activity. Furthermore, carotenoid stability was monitored for 90 days at 25 and 4 °C. Confocal and SEM microscopy revealed morphological differences among samples. α- and β-CDs spontaneously associated into microcrystals assembling in thin spherical shells (cyclodextrinosomes, Ø ≈ 27 µm) at the oil/water interface. Much smaller (Ø ≈ 9 µm) aggregates were occasionally observed with γ-CDs, but most TO droplets appeared “naked”. FTIR and DSC spectra indicated that most CDs did not participate in TO complex formation, nevertheless structurally different interfacial complexes were formed. The trolox equivalent antioxidant capacity (TEAC) activity of emulsions and powders highlighted better performances of α- and β-CDs as hydrophobic antioxidants-dispersing agents across aqueous media. Regardless of CDs type, low temperature slowed down carotenoid degradation in all samples, except all-[E]-lycopene, which does not appear efficiently protected by any CD type in the long storage period.

Buspirone loaded solid lipid nanoparticles for amplification of nose to brain efficacy: Formulation development, optimization by Box-Behnken design, in-vitro characterization and in-vivo biological evaluation

The strategies to avoid blood brain barrier are been explored to improve brain targeting therapeutics in order to ensure potential prospects of nose to brain delivery. In this research work, Buspirone (BUS) loaded solid lipid nanoparticles (SLNs) for nose to brain delivery were prepared by solvent free technique and optimized by three factors and three levels Box- Behnken design. The three independent variables viz, drug (BUS) to lipid (Compritol® 888 ATO) ratio (labeled A), surfactant concentration (tween 80+ poloxamer, 2:1- labeled B) and sonication time (labeled C) were selected in range of 1:3–1:5, 1–2% and 5–15 min respectively. Their influences on particle size (nm, labeled Y1), Polydispersity index (PDI, labeled Y2) and % entrapment efficiency (labeled Y3) were observed. Optimized batch (B-OP3) showed spherical morphology possessing the value of particle size, PDI, zeta potential, entrapment efficiency, and in-vitro drug release as 218.60 ± 9.18 nm, 0.305 ± 0.012, −26.47 ± 2.36 mV, 70.13 ± 4.21% and 93.36 ± 8.63% respectively. BUS-SLNs displayed superior ex-vivo permeation profiles as compared to BUS-Sol. X-ray diffraction and differential scanning calorimetry spectra do not display the characteristic peak of BUS, thus recommending the entrapment of drug in lipid core. AUC 0-∞ in the brain for BUS-SLNs i.n was found to be 2.18 times more than BUS-Sol i.n and 2.66 times more than BUS-SLNs i.v., thus supporting improved targeting efficiency of developed SLNs. The value of drug targeting efficiency (DTE) percentage to brain (882.59%) and nose to brain direct transport (DTP) percentage (88.67%) for BUS-SLNs i.n was higher as compared to BUS-Sol i.n (DTE = 238.63%, DTP = 58.09%). Furthermore, confocal laser scanning microscopy study confirmed that brain targeting of BUS-SLNs was better than BUS-Sol when administered intranasally. Finally, results revealed that SLNs establish itself as a potential drug delivery system for brain delivery of BUS via intranasal route.

Kinetic analysis of non‐isothermal oxidation of bioactive milk lipids

AbstractThe oxidation of pure docosahexaenoic acid (DHA, C22:6 ω3), eicosapentaenoic acid (EPA, C20:5 ω3), conjugated linoleic acid (CLA, C18:2), and trans‐vaccenic acid (TVA, C18:1 t11) was assessed using differential scanning calorimetry (DSC) at six heating rates (3–18 K min−1) within a range of 300–600 K. The DSC spectra were analyzed using iso‐conversional kinetics to calculate the pre‐exponential factor (Ao), activation energy (Eo), and reaction model (f(α)). The Eo for DHA, EPA, CLA, and TVA varied from 33–40, 36–49, 48–64, and 64–92 kJ/mol, respectively. The Ao were 2.87 ± 0.03, 4.42 ± 0.21, 24.94 ± 1.31, and 580.91 ± 4.61 min−1 for DHA, EPA, CLA, and TVA, respectively. The comparison of the numerically reconstructed model with theoretical values showed that the oxidation of DHA and EPA was best described by an Avrami‐Erofeev model, while a three‐dimensional diffusion model best described the oxidation of CLA and TVA.Practical applicationsThe application of iso‐conversional kinetics to study the oxidation of bioactive milk lipids provides a mathematical tool for describing the oxidation regardless of the complexity of the process. The oxidation of bioactive milk lipids can be modeled using the obtained values of the kinetic triplet. Such modeling can be performed without knowing the mechanisms, which typically involves the use of sophisticated analytical techniques. The obtained results may enable further process development, design, and optimization.

The Onset and Solidification Path of a Basaltic Melt by in situ Differential Scanning Calorimetry (DSC) and ex situ Investigations

The in-situ differential scanning calorimetry (DSC) technique has been applied to investigate the solidification paths of a basaltic liquid. The starting glass was heated up to 1300 °C, kept at this superliquidus temperature for 2 h and cooled at rates (∆T/∆t) of 7, 60, 180, 1000, and 1800 °C/h, down to 800 and 600 °C. Glass transition temperature (Tg), crystallization temperature (Tx_HR) and melting temperature (Tm) were measured by in-situ DSC spectra on heating. Tx measured along the cooling paths (Tx_CR) shows exothermic peaks that change from a single symmetric shape (7 and 60 °C/h) to multi-component patterns (180, 1000 and 1800 °C/h). The recovered products characterized by FE-SEM and EPMA-WDS show a phase assemblage of spinel (sp), clinopyroxene (cpx), melilite (mel), plagioclase (plg), and glass. Moreover, crystal size distributions (CSDs) and growth rates (Gmax and GCSD) were also determined. The crystal content slightly increases from 7 to 1800 °C/h. Faceted sp are present in all the run products with an amount always < 2 area%. Cpx increases from 7 to 1800 °C/h, changing its texture from almost faceted to dendritic between 60 and 180 °C/h. The area% of mel follows an asymmetric Gaussian trend, while plg nucleates only at 7 °C/h with a content < 2 area%. The coupling of DSC and SEM outcomes indicate that sp nucleate first, followed by cpx and mel (and/or plg). The increment of ∆T/∆t causes an increase of the CSD slope (m) and crystal population density per size (n0), as well as a decrease of the crystal size, for both cpx and sp. The log-linear CSD segments with different slopes at 7 and 60 °C/h suggest multiple nucleation events and crystal growth by coarsening. Gmax and GCSD for cpx and sp directly measured on the actual crystallization time by DSC spectra, both increase with the increasing of ∆T/∆t. The onset temperature of crystallization (Txi) decreases as ∆T/∆t increases, following an exponential trend that defines the uppermost portion of a time-transformation-temperature (TTT)-like curve. This analytical model allows us to quantitatively model the kinetic crystallization paths of dry basalts.

Design and Preparation of Zaltoprofen-Nicotinamide Pharmaceutical Cocrystals via Liquid Assisted Grinding Method

Abstract: Introduction: Pharmaceutical cocrystal is an endowed approach to augment solubility and dissolution of drugs with limited aqueous solubility. Zaltoprofen is a nonsteroidal anti-inflammatory drug with prevailing solubility problem. The present study deciphers preparation of cocrystals of lipophilic drug zaltoprofen to improve the solubility and dissolution by screening various coformers. Methods: Cocrystals of zaltoprofen were prepared in 1:1 and 1:2 molar ratio of drug: coformer by liquid assisted grinding method. The crystalline phase was subjected to evaluation by melting point and solubility. The potential cocrystals were characterized by differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). Dissolution rate and stability of cocrystals was also investigated. Results: Zaltoprofen-nicotinamide (ZFN-nicotinamide) cocrystals revealed variation in melting point and solubility. Two cocrystals were obtained in 1:1 and 1:2 ratios with nicotinamide. IR spectrum distinctly showed the shifting of typical absorption bands of zaltoprofen. Crystallinity of cocrystals was clear from the PXRD pattern and noteworthy difference in 2θ value of intense peaks. DSC spectra of cocrystals revealed altered endotherms analogous to melting point. Cocrystals exhibited rapid dissolution rate and 56% increase in the extent of dissolution compared to pure drug. The cocrystals were found stable at stability conditions. SEM revealed difference in the crystal morphology. Conclusion: Hence, it can be concluded that ZFN-nicotinamide cocrystal could present an improved drug design approach to surmount dissolution and bioavailability related challenges linked with lipophilic drug zaltoprofen. Key words: Cocrystal, Zaltoprofen, Liquid assisted grinding, Solubility, Dissolution.

Superior Solubility and Dissolution of Zaltoprofen via Pharmaceutical Cocrystals.

Pharmaceutical cocrystals are a promising tool to enhance the solubility and dissolution of poorly soluble drugs. Zaltoprofen (ZFN) is nonsteroidal anti-inflammatory drug with a prevalent solubility problem. The present study was undertaken to enhance the solubility and dissolution of ZFN through pharmaceutical cocrystals by screening various coformers. Cocrystals of ZFN were prepared in 1:1 and 1:2 ratio of drug:coformer by the dry grinding method. The melting point and solubility of the crystalline phase were determined. The potential cocrystals were characterized by differential scanning calorimetry (DSC), infrared spectroscopy, and powder X-ray diffraction (PXRD). Cocrystals were subjected to dissolution rate and stability study. ZFN-nicotinamide (NIC) cocrystals demonstrated deviation in melting point and solubility. The cocrystals were obtained in both 1:1 and 1:2 ratios with NIC. The infrared analysis noticeably indicated the shifting of characteristic bands of ZFN. The crystallinity of the cocrystals was evident from the XRPD pattern and notable difference in the 2θ values of intense peaks. The DSC spectra of the cocrystals exhibited altered endotherms analogous to melting point. The cocrystals showed a faster dissolution rate and a 55% increase in the extent of dissolution compared to pure drug. The cocrystals were stable at room temperature and accelerated conditions. The prepared cocrystals exhibited greater solubility and dissolution compared to the pure drug and were stable at room temperature and accelerated conditions.

Formulation Development of Immediate Release Solid Dispersion Tablets of Lovastatin with Enhanced Dissolution

The objectives and purpose of the present research work are to improve the solubility and dissolution rate of lovastatin. Solid dispersions of lovastatin were prepared by fusion method by using two selected hydrophilic meltable carriers vis-a-vis gelucire 44/14 and polyethyleneglycol (PEG6000). Neucilin US2 was used as an adsorbent, flow and compressibility promoter and booster. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Fourier transform infrared spectra (FT-IR), differential scanning calorimetry (DSC) and in-vitro dissolution. Solubility studies showed 8 and 15 fold maximization in solubility for PEG6000 and gelucire 44/14 based solid dispersions respectively. The Gibbs free energy ΔGtr° values were negative for both the carriers indicating spontaneous nature of solubilization. FT-IR and DSC spectra demontrated that drug and carriers are compatible with each other. In-vitro dissolution studies demontrated that gelucirre 44/14 based solid dispersion dissolved more than 95% of lovastatin within 30 min. Solid dispersion exhibiting highest solubility and dissolution rate was compressed and formulated into immediate release (IR) tablets incorporating crosscaramellose sodium as superdisintegrant. In vitro dissolution studies for solid dispersion based immediate release tablet, exhibited more than 90% drug dissolution in 30 min(F28). The adsorbent, Neucilin US2 reduced stickiness, imparted good flow and compressibility to solid dispersions. Among the two carriers, gelucire 44/14 demonstrated better solubility and dissolution enhancement potential for lovastatin.

Solubility and Solution Thermodynamics of Baricitinib in Six Different Pharmaceutically Used Solvents at Different Temperatures

Abstract The preset study was undertaken to determine solubility and solution thermodynamics of a novel anticancer drug baricitinib in some pharmaceutically used mono/pure solvents including “water, ethanol, polyethylene glycol-400 (PEG-400), ethyl acetate (EA), dichloromethane (DCM) and dimethyl sulfoxide (DMSO)” at “T = 298.2 K to 323.2 K” and “p = 0.1 MPa”. The solubility of baricitinib after equilibrium (saturation state) was analyzed spectrophotometrically by applying an isothermal technique. Characterization of solid phases of initial and equilibrated baricitinib was confirmed with the help of differential scanning calorimetry (DSC). Measured solubilities of baricitinib were regressed using “van’t Hoff and Apelblat models”. DSC spectra of baricitinib showed no change in physical state of baricitinib after equilibrium. Solubilities of baricitinib (as mole fraction) were estimated highest in DMSO (1.65 × 10−1) followed by PEG-400 (1.42 × 10−1), DCM (1.29 × 10−3), ethanol (7.41 × 10−4), EA (4.74 × 10−4) and water (1.76 × 10−4) at “T = 323.2 K” and same tendencies were also noted at other temperatures studied. With the help of theoretical solubilities of baricitinib, activity coefficients were estimated. The estimated data of activity coefficients indicated higher molecular interactions in baricitinib-DMSO and baricitinib-PEG-400 as compared with baricitinib-water, baricitinib-EA, baricitinib-DCM and baricitinib-ethanol. Thermodynamic treatment of solubility values of baricitinib showed “endothermic and entropy-driven dissolution” of baricitinib in all pharmaceutically used solvents evaluated.