Ultrasound-assisted preparation of novel ibuprofen-loaded excipient with improved compression and dissolution properties

Context: Most of the active pharmaceutical ingredients (APIs) suffer from a drawback of poor aqueous solubility. In addition to the same, some APIs show poor tabletting behavior creating problems in formulation development. Crystal engineering can be an efficient tool in rectification of such problems associated with the APIs. Thus present work deals with crystallization of ibuprofen (a model drug) onto the surface of dicalcium phosphate (DCP) particles using different techniques.

Objective: The objective of the present work was to prepare ibuprofen-loaded DCP particles and further to analyze them for compressibility and dissolution behavior.

Materials and methods: Various crystallization techniques such as solvent evaporation (SE), melt crystallization (MC), melt sonocrystallization (MSC), antisolvent crystallization (AC), and antisolvent sonocrystallization (ASC) were screened for the preparation of ibuprofen-loaded DCP. Products obtained from different techniques were analyzed for physicochemical, micromeritic and compression properties.

Results and discussion: ASC technique was found to be suitable for preparing directly compressible ibuprofen-loaded DCP particles. The change in the crystal habit (needle to plate shape) of ibuprofen and its crystallization in miniscular form onto the surface of DCP particles showed significant improvement in the dissolution rate and compression properties of ibuprofen due to an increase in specific surface area when compared with ibuprofen crystallized by other techniques. Additionally, the tablets prepared from ASC powder did not require binder since ibuprofen acted as melt binder during compression.

Conclusion: Directly compressible ibuprofen-loaded DCP particles can serve as an alternative for conventional ibuprofen tablets prepared by wet granulation technique.     

Spark Plasma Sintering of Nanostructured Aluminum: Influence of Tooling Material on Microstructure

The influence of tooling material, i.e., graphite and WC-Co, on the microstructure of a spark plasma sintering (SPS) consolidated, nanostructured aluminum alloy is studied in this paper. The results show that tooling selection influences microstructure evolution, independent of process parameters. The influence of tooling on microstructure is rationalized on the basis of the following factors: heating rate, electrical current density, localized heating, and imposed pressure. A theoretic framework, based on the physical properties of graphite and WC-Co, is formulated to explain the observed behavior.     

Metabolites and Genes behind Cardiac Metabolic Remodeling in Mice with Type 1 Diabetes Mellitus

Metabolic remodeling is at the heart of diabetic cardiomyopathy. High glycemic fluctuations increase metabolic stress in the type 1 diabetes mellitus (T1DM) heart. There is a lack of understanding on how metabolites and genes affect metabolic remodeling in the T1DM heart. We hypothesize that differential expression of metabolic genes and metabolites synergistically influence metabolic remodeling preceding T1DM cardiomyopathy. To test our hypothesis, we conducted high throughput analysis of hearts from adult male hyperglycemic Ins2^+/− (Akita) and littermate normoglycemic Ins2^+/+ (WT) mice. The Akita mouse is a spontaneous, genetic model of T1DM that develops increased levels of consistent glycemic variability without the off-target cardiotoxic effects present in chemically- induced models of T1DM. After validating the presence of a T1DM phenotype, we conducted metabolomics via LC-MS analysis and genomics via next-generation sequencing in left ventricle tissue from the Akita heart. Ingenuity Pathway Analyses revealed that 108 and 30 metabolic pathways were disrupted within the metabolomics and genomics datasets, respectively. Notably, a comparison between the two analyses showed 15 commonly disrupted pathways, including ketogenesis, ketolysis, cholesterol biosynthesis, acetyl CoA hydrolysis, and fatty acid biosynthesis and beta-oxidation. These identified metabolic pathways predicted by the differential expression of metabolites and genes provide the foundation for understanding metabolic remodeling in the T1DM heart. By limited experiment, we revealed a predicted disruption in the metabolites and genes behind T1DM cardiac metabolic derangement. Future studies targeting these genes and metabolites will unravel novel therapies to prevent/improve metabolic remodeling in the T1DM heart.     

O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6-benzylguanine derivatives and their rate of hydrolysis by cellular esterases

To modulate the bioavailability and perhaps improve the tumor cell selectivity of O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT inactivators and as substrates for cellular esterases. The potential prodrugs examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7- and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9-esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8-bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at least 75 times less potent than the corresponding benzylated purine against the pure human AGT. In contrast, the activities of esters and their respective benzylated purine were similar in crude cell extracts and in intact cells. The increase in potency of esters in cellular extracts could be explained by a conversion of the respective prodrug to the more potent benzylated purine in the presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor cell hydrolysis of the esters varied considerably as a function of cell type and prodrug structure. These data suggest that these or related prodrugs may be advantageous for selective AGT inactivation in certain tumor types.     

Lead sorption onto ferrihydrite. 3. Multistage contacting

Few studies have demonstrated the practical application of surface complexation models, calibrated with fundamental macroscopic and spectroscopic metal sorption data, in helping to solve industrial trace metal emissions problems. In this work, multistage ferrihydrite sorption systems are evaluated for their effectiveness in reducing single-solute lead(II) [Pb(II)] concentrations in contaminated water streams to very low levels. Experimental data and modeling results indicate that a multistage sorption system can significantly reduce Pb(II) effluent concentrations for the same total amount of sorbent or, alternatively, dramatically lower total sorbent consumption for the same effluent Pb(II) concentration. Model predictions were generated using a steady-state, multistage, equilibrium adsorber model that was specifically developed for and integrated into 0LI Systems' Environmental Simulation Program. The modified triple-layer model was used to simulate Pb(II) surface-liquid equilibria within the adsorber model. Engineering screening evaluations indicate that a 2-3-stage sorption process can provide significant economic savings when compared to a 1-stage process operating with the same target effluent Pb(II) concentration. Additional equilibrium stages beyond 2 or 3 provide diminishing economic returns. The major economic driver for multiple contacting stages is reduced capital investment and operating costs for sludge handling, dewatering, and disposal.     

Phenolic Content and Antioxidant Activity of Germinated and Cooked Pulses

Five commonly consumed pulses, Mah (Vigna mungo), Green mung (Vigna radiata), Arhar (Cajanas cajan), Masur (Lens esculantus), and Moth (Vigna aconitifolia), were studied for their total phenolic content and antioxidant activity after germination (12 and 24 h) and pressure cooking. Arhar had the highest total phenolic content (6.71 mg ferulic acid/g flour) whereas Moth had the least (1.54 mg/g). All pulses, except Moth, showed a significant decrease in total phenolic content after germination. The antioxidant activity of the pulses varied from 10.61 to 36.38% (DPPH radical scavenging activity), which significantly decreased with germination in all pulses except Moth. The total phenolic content highly correlated with the antioxidant activity in the pulses. Cooking lowered the total phenolic content by 10–45% and antioxidant activity by 27–68% in the control and germinated pulses.     

Extrusion of Hulled Barley Affecting β-Glucan and Properties of Extrudates

Grits from eight different hulled barley cultivars were subjected to extrusion cooking on a twin screw extruder, and the effect of extrusion variables (temperature and moisture) on β-glucan and physicochemical properties was evaluated. The highest bulk density was observed for extrudates extruded at 150 °C and 20% moisture (low temperature high moisture, LTHM) while the highest expansion was observed for the extrudates extruded at 150 °C and 15% moisture (low temperature low moisture). Extrusion reduced the lightness (L*) of the extrudates and the highest decrease observed for LTHM extrudates. Increasing the feed moisture decreased water solubility index (WSI) significantly while increasing the extrusion temperature significantly increased WSI. The high temperature high moisture (HTHM) extrudates exhibited the highest water absorption capacity. The total β-glucan content was not affected by extrusion cooking, but a significant increase in soluble β-glucan was observed with the highest in high temperature low moisture extrudates. The ratio of soluble to insoluble β-glucan varied from 0.7 to 1.5 in the control barley, but after extrusion cooking, the ratio was changed from 1.2 to 3.1. The β-glucan extractability increased by up to 8% after extrusion with extrudates from HTHM showing the highest extractability. The extent of starch gelatinization varied from 80% to 100% upon extrusion, and the highest was observed in HTHM extrudates. A significant decrease in the peak and final viscosity of the extrudates at all the extrusion conditions was observed.     

A survey on review summarization and sentiment classification

Knowledge and Information Systems - With increasingly more people using online services, purchasing products, and reviewing them, it becomes crucial to have a system that can provide a crisp...     

Enhancing the isolation between the strips of dipoles antenna at terahertz frequency with cuboid-shaped graphene layer

Wireless Networks - In this paper, the concept of mantle cloaking method uses to enhance the isolation between the two electrically close dipole antenna at low-terahertz (THz) frequencies, two...