In vitro evaluation and in vivo performance of lyophilized gliclazide

Enhancement of the dissolution rate of the poorly water-soluble hypoglycemic agent, gliclazide, by the aid of lyophilization was investigated. Mannitol, sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP-k-30) were employed in different weight ratios (43%, 56% and 64% w/w, respectively) as water-soluble excipients in the formulation. Lyophilized systems were found to exhibit extremely higher in vitro dissolution rate compared to the unprocessed drug powder. Solid state characterization of the lyophilized systems using X-ray powder diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry techniques revealed that dissolution enhancement was attributable to transformation of gliclazide from the crystalline to an amorphous state in the solid dispersion formed during the lyophilization process. The gastrointestinal absorption and hypoglycemic effect of the lyophilized gliclazide/SLS system were investigated following oral administration to Albino rabbits. C_max and area under the plasma concentration–time curve of gliclazide (AUC_0–12) after administration of the lyophilized formulations were significantly higher than those obtained after administration of the unprocessed gliclazide.     

Formation of Chlorotriophenoxy Radicals from Complete Series Reactions of Chlorotriophenols with H and OH Radicals

The chlorothiophenoxy radicals (CTPRs) are key intermediate species in the formation of polychlorinated dibenzothiophenes/thianthrenes (PCDT/TAs). In this work, the formation of CTPRs from the complete series reactions of 19 chlorothiophenol (CTP) congeners with H and OH radicals were investigated theoretically by using the density functional theory (DFT) method. The profiles of the potential energy surface were constructed at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. The rate constants were evaluated by the canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) contribution at 600–1200 K. The present study indicates that the structural parameters, thermal data, and rate constants as well as the formation potential of CTPRs from CTPs are strongly dominated by the chlorine substitution at the ortho-position of CTPs. Comparison with the study of formation of chlorophenoxy radicals (CPRs) from chlorophenols (CPs) clearly shows that the thiophenoxyl-hydrogen abstraction from CTPs by H is more efficient than the phenoxyl-hydrogen abstraction from CPs by H, whereas the thiophenoxyl-hydrogen abstraction from CTPs by OH is less impactful than the phenoxyl-hydrogen abstraction from CPs by OH. Reactions of CTPs with H can occur more readily than that of CTPs with OH, which is opposite to the reactivity comparison of CPs with H and OH.     

Physical Stability of Octenyl Succinate–Modified Polysaccharides and Whey Proteins for Potential Use as Bioactive Carriers in Food Systems

The high cost and potential toxicity of biodegradable polymers like poly(lactic‐co‐glycolic)acid (PLGA) has increased the interest in natural and modified biopolymers as bioactive carriers. This study characterized the physical stability (water sorption and state transition behavior) of selected starch and proteins: octenyl succinate–modified depolymerized waxy corn starch (DWxCn), waxy rice starch (DWxRc), phytoglycogen, whey protein concentrate (80%, WPC), whey protein isolate (WPI), and α‐lactalbumin (α‐L) to determine their potential as carriers of bioactive compounds under different environmental conditions. After enzyme modification and particle size characterization, glass transition temperature and moisture isotherms were used to characterize the systems. DWxCn and DWxRc had increased water sorption compared to native starch. The level of octenyl succinate anhydrate (OSA) modification (3% and 7%) did not reduce the water sorption of the DWxCn and phytoglycogen samples. The Guggenheim–Andersen–de Boer model indicated that native waxy corn had significantly (P < 0.05) higher water monolayer capacity followed by 3%‐OSA‐modified DWxCn, WPI, 3%‐OSA‐modified DWxRc, α‐L, and native phytoglycogen. WPC had significantly lower water monolayer capacity. All Tg values matched with the solid‐like appearance of the biopolymers. Native polysaccharides and whey proteins had higher glass transition temperature (Tg) values. On the other hand, depolymerized waxy starches at 7%‐OSA modification had a “melted” appearance when exposed to environments with high relative humidity (above 70%) after 10 days at 23 °C. The use of depolymerized and OSA‐modified polysaccharides blended with proteins created more stable blends of biopolymers. Hence, this biopolymer would be suitable for materials exposed to high humidity environments in food applications.     

Towards optimization of the osmotic drying process of alumina-gelatin objects: Regression analysis and verification

In this study, further analysis of the osmotic drying process was conducted to identify the optimum combination of parameters for drying rectangular alumina-gelatin beams. This study was designed to determine the effect of three variables related to the osmotic drying process (osmotic pressure, molecular weight, and immersion time) on the interaction between the liquid desiccant and the submerged alumina-gelatin samples. The water loss from the alumina-gelatin samples was positively correlated with the molecular weight, osmotic pressure, and immersion time. Up to 40% by weight of the initial water content was removed during the osmotic drying process. The samples also experienced solids gain due to the counterflow of solute from the liquid desiccant. The least amount of solids gain resulted from drying for the shortest immersion time at low osmotic pressure and high molecular weight. Evidence of possible interactions between variables was noted for the sintered density metric. Statistical methods were used to form regression equations for the measured responses (water loss, solids gain, bulk density). A verification experiment was conducted to compare the experimental outcomes to the predicted outcomes. The responses were simultaneously optimized to identify the combination of variable settings required to meet specified goals. In order to maximize water loss, minimize solids gain, and maximize bulk density, the ceramic-gelatin object should be immersed for approximately 60?min in an aqueous solution of 100,000?g/mol poly(ethylene oxide) at an osmotic pressure of 2.50?MPa. These values are valid for the range of parameter settings tested and the sample fabrication and drying methods used.