Characterization of the absorption of theophylline from immediate- and controlled-release dosage forms with a numerical approach using the in vitro dissolution-permeation process using caco-2 cells

After oral administration, drug absorption rate is recognized to be dependent on two major factors: dissolution and intestinal cells permeability. Caco-2 monolayer cells have been largely used as a permeation study model. In this study, a numerical approach funded on an exponential first-order time relationship was tested to compare immediate- and controlled-release tablets of theophylline using a dissolution-permeation system. The dissolution performance using USP II paddle apparatus was coupled to the permeability studies investigated in Caco-2 cell monolayers. The dissolved samples were taken at different times; their pH and osmolarity were adjusted to render them suitable to Caco-2 permeability studies (osmolarity = 300 mosm, pH = 7.4). The experimental data show that the dissolution fits the exponential first-order relationship rate. The permeability values were in a range of 4.45 10(- 6)-5.28 10(- 6) cm/s, and percentages of absorbed drug dose were dependent on the fraction initially present in the donor compartment, indicating that absorption of theophylline was dissolution rate limited. Plotting experimental absorbed fractions (F(a)) against experimental dissolved fractions (F(d)) show that permeation is the rate-limiting step in drug absorption process in the extended release form of theophylline. Our results demonstrate a general agreement between observed F(a)/F(d) relationships and theoretical F(a)/F(d) relationships obtained with our approach funded on dissolution and permeation behavior. We concluded that the couple dissolution-caco-2 system could be a useful tool to characterize intestinal permeation for a new formulation of a drug compared with the conventional one.     

Bioreactors Based on Monolith‐Supported Ionic Liquid Phase for Enzyme Catalysis in Supercritical Carbon Dioxide

Bioreactors with covalently supported ionic liquid phases (SILP) were prepared as polymeric monoliths based on styrene–divinylbenzene or 2‐hydroxyethyl methacrylate–ethylene dimethacrylate, and with imidazolium units loadings ranging from 54.7 to 39.8 % wt IL per gram of polymer. The SILPs were able to absorb Candida antarctica lipase B (CALB), leading to highly efficient and robust heterogeneous biocatalysts. The bioreactors were prepared as macroporous monolithic mini‐flow systems and tested for the continuous flow synthesis of citronellyl propionate in supercritical carbon dioxide (scCO₂) by transesterification. The catalytic activity of these mini‐flow‐bioreactors remained practically unchanged for seven operational cycles of 5 h each in different supercritical conditions. The best results were obtained when the most hydrophobic monolith, M‐SILP‐ 8 ‐CALB, was assayed at 80 °C and 10 M Pa, reaching a total turnover number (TON) of 35.8×10⁴ mol product/mol enzyme. The results substantially exceeded those obtained for packed‐bed reactors with supported silica‐CALB‐Si‐4 catalyst under the same experimental conditions.     

Extraction and functional properties of gelatin from the skin of cuttlefish (Sepia officinalis) using smooth hound crude acid protease-aided process

The characteristics and functional properties of gelatin from skin cuttlefish (Sepia officinalis) were investigated and compared to those of halal bovine gelatin (HBG). The gelatin extraction efficiency was improved by an acid-swelling process in the presence of smooth hound crude acid protease extract (SHCAP). The yields of gelatins from cuttlefish skin after 48 h with acid and with crude acid protease (15 units/g alkaline-treated skin) were 2.21% and 7.84%, respectively. The gelatin from skin cuttlefish had high protein (91.35%) but low fat (0.28%) contents. Compared to HBG, the cuttlefish-skin gelatin (CSG) has different amino acids composition than halal bovine gelatin. CSG contained slightly low hydroxyproline and proline (180‰) than HBG (219‰), whereas the content of serine was higher (49‰ versus 29‰). The gel strength of the gelatin gel from CSG (181 g) was lower than that of HBG (259 g) (p < 0.05) possibly due to lower hydroxyproline content. Cuttlefish-skin gelatin exhibited a similar emulsifying activity but greater emulsifying and foam stability than the halal bovine gelatin (p < 0.05). Foam formation ability, foam stability and water-holding capacity of CSG were slightly lower than those of the HBG, but fat-binding capacity was higher in the cuttlefish gelatin.     

Anisakis simplex s.l. parasitization in mackerel (Scomber japonicus) caught in the North of Morocco--prevalence and analysis of risk factors

Consumption of mackerel (Scomber japonicus) is very widespread in Morocco, where its production is an important economic pillar. We investigated the prevalence of infection by Anisakis spp. in mackerel caught in Moroccan waters, analyzing infection risk factors. The prevalence was generally higher in fish from the Atlantic (67.9%) than from the Mediterranean (57.0%), but they did not differ in the mean abundance, intensity, or prevalence of muscle parasitization. A. pegreffii was the predominant species (82.6% of larvae) followed by the hybrid A. simplex s.s./A. pegreffii (16.3%). Only one L3 of A. simplex s.s. was found in a specimen of S. japonicus from the Atlantic. Mackerel infection was associated with total fish weight, gonad weight, catch area, and catch season. However, muscle infection was associated solely with total weight and parasite loads. The consumption of lower-weight mackerel may be a good prophylactic measure against human anisakiasis.     

Crosstalk of Diabetic Conditions with Static Versus Dynamic Flow Environment—Impact on Aortic Valve Remodeling

Type 2 diabetes mellitus (T2D) is one of the prominent risk factors for the development and progression of calcific aortic valve disease. Nevertheless, little is known about molecular mechanisms of how T2D affects aortic valve (AV) remodeling. In this study, the influence of hyperinsulinemia and hyperglycemia on degenerative processes in valvular tissue is analyzed in intact AV exposed to an either static or dynamic 3D environment, respectively. The complex native dynamic environment of AV is simulated using a software-governed bioreactor system with controlled pulsatile flow. Dynamic cultivation resulted in significantly stronger fibrosis in AV tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on fibrosis. The expression of key differentiation markers and proteoglycans were altered by diabetic conditions in an environment-dependent manner. Furthermore, hyperinsulinemia and hyperglycemia affect insulin-signaling pathways. Western blot analysis showed increased phosphorylation level of protein kinase B (AKT) after acute insulin stimulation, which was lost in AV under hyperinsulinemia, indicating acquired insulin resistance of the AV tissue in response to elevated insulin levels. These data underline a complex interplay of diabetic conditions on one hand and biomechanical 3D environment on the other hand that possesses an impact on AV tissue remodeling.     

Chemiluminescence of isotactic polypropylene induced by photo‐oxidative degradation and natural weathering

The analysis of the chemiluminescence (CL) kinetic parameters (induction time, oxidation rate, and activation energy) after the UV irradiation and outdoor exposure of isotactic polypropylene (i‐PP) films have been studied. The initial CL emission intensity increased with increasing photodegradation time of i‐PP films. On photodegradation, the activation energies were found to decrease linearly with time of UV‐irradiation and outdoor exposure. The slopes of these linear dependences were used to indicate the degree of photodegradation of the polymer and also for the characterization of the stabilizing effect of the additive. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4623–4629, 2006     

Changes in nutritional and sensory properties of orange juice packed in PET bottles: An experimental and modelling approach

Sensitivity to oxidation of an orange juice was investigated through packaging in standard PET or active PET with oxygen scavenger bottles. The evolution of dissolved oxygen was found to be similar in all bottles, whereas ascorbic acid degradation was related to the oxygen transfer with higher losses in standard PET (53%) against active PET (31%). Moreover, when juice was exposed to high intensity light, a fold faster degradation of ascorbic acid was observed compared to total darkness. Depending also on the light intensity and regardless of the package permeability, changes in the aromatic profile of the juice were observed due to the degradation of limonene and the formation of α-terpineol, an off-flavour. A mechanistic model was developed to predict the shelf life of orange juice. This model, coupling O₂ transfer and ascorbic acid oxidation reaction in the bottled juice, confirmed that oxygen permeation through packaging material could not be neglected.     

Anticoagulant activities of goby muscle protein hydrolysates

The anticoagulant activities of protein hydrolysates prepared from goby muscle by treatment with various bacterial alkaline proteases were investigated. All proteases exhibited varying degrees of hydrolysis (DH) and all goby protein hydrolysates (GPHs) caused a significant prolongation of both the thrombin time (TT) and the activated partial thromboplastin time (APTT). The hydrolysate generated by the crude protease from Bacillus licheniformis NH1 displayed the highest anticoagulant activity, and the higher TT (about 32 s) at a concentration of 5 mg/mL was obtained with hydrolysate having a DH of 8.86%. This hydrolysate was then fractionated by size exclusion chromatography on a Sephadex G-25 column into five major fractions (F1–F5). Fraction F2, which exhibited the highest anticoagulant activity, was then fractionated by reversed-phase high-performance liquid chromatography. The molecular masses and amino acid sequences of four peptides in peptide sub-fraction F2–6, which exhibited the highest anticoagulant activity, were determined using ESI-MS and ESI-MS/MS, respectively. The structures of these peptides were identified as Leu-Cys-Arg, His-Cys-Phe, Cys-Leu-Cys-Arg and Leu-Cys-Arg-Arg.     

Long‐term microstructural changes in solid oxide fuel cell anodes: 3D reconstruction

Microstructural changes in solid oxide fuel cell anodes after long‐term operation have been characterized by sequential sectioning with a focused ion beam, followed by scanning electron microscopy imaging and three‐dimensional reconstruction. The anodes were porous composites of Ni and Y₂O₃‐stabilized ZrO₂ (YSZ). The cells were operated at 800°C for 2, 4, and 8 kh, and at 925°C for 2 and 4 kh. For each specimen, the volume fraction, surface area, particle diameter, and tortuosity have been calculated for each phase (Ni, YSZ, and pores). The dependence of these microstructural parameters on the volume of sample analyzed was monitored; sufficiently large volumes were analyzed so as to eliminate any effect of sample volume. Gradients in volume fraction of Ni and porosity developed during fuel cell operation, with Ni fraction increasing, and pore fraction decreasing, at the electrolyte/anode interface. The magnitudes of these gradients increased with time.     

Kinetic Study of Hindered Amine Light Stabilizer Photografting in Poly(propylene) Films under Natural Weathering and Accelerated UV Conditions: Effect of Additive Concentration

Full Paper: The objective of this work is aimed at determining the kinetics of HALS photografting in PP films as a function of the additive concentration under both natural weathering and accelerated UV conditions. The stabilizer studied had a single structure that combined HALS and a UV absorbing unit detectable at 308 nm in the UV spectrum of PP, capable of inducing a photoreaction with the polymer matrix. The kinetics of HALS photografting on PP films at various additive concentrations was determined by direct spectroscopic measurements on film samples through the absorption band of the stabilizer positioned at 308 nm in the UV spectra, which was attributed to the highly conjugated methylenic double bond. The content of free HALS was determined as a function of exposure time by UV spectroscopy for all the additive concentration ratios used. It is shown that the kinetics of HALS photografting increase with a decrease in the additive concentration ratio. The whole grafting process under conditions of natural weathering occurred in the PP film after almost 350 h of exposure, while approximately 20 h were necessary under accelerated UV conditions. Moreover, these kinetics are well described by a third order polynomial model, validated by a maximum value of the coefficient of correlation close to unity. This was also confirmed by a comparison of the time values measured at 50% of the total grafting calculated from the model with those observed experimentally. This finding was consistent with the data obtained on the free HALS content determined by UV spectroscopy.

The percentage of HALS photografting in PP films as a function of time under natural weathering, determined by UV spectroscopy.