Anomalous Diffusion Mechanism Research Articles

Anomalous Diffusion Mechanism for Water in Native and Hydrophobically Modified Starch Using Fractional Calculus

Anomalous Diffusion Mechanism for Water in Native and Hydrophobically Modified Starch Using Fractional Calculus

Formulation of novel functional extrudates containing natural bioactive compounds

Incorporating natural antimicrobial agents into food systems is a promising alternative to synthetic additives. This study developed corn-based functional extrudates enriched with essential oils from oregano, rosemary, chamomile, and hypericum (EOB) via twin screw extrusion processing. EOB was introduced in both encapsulated and non-encapsulated forms using electrohydrodynamic processing, spray drying, and freeze drying within a whey protein isolate and pullulan matrix. Extrudates containing spray-dried EOB (SP-EOB) achieved the highest extrusion efficiency (72.94% ± 1.16%). Morphological analysis revealed homogeneous structures for XE and XS extrudates, while XF extrudates were more porous. The gastrointestinal release kinetics of EOB from the extrudates were best described by the Korsmeyer-Peppas model, indicating an anomalous diffusion mechanism with “n” values ranging from 0.480 to 0.650. These findings highlight the potential for naturally bioactive and sustainable food products via advanced processing methods, reducing dependence on synthetic additives.

A Novel Phytotherapy Application: Preparation, Characterization, Antioxidant Activities and Determination of Anti-inflammatory Effects by In vivo HET-CAM Assay of Chitosan-based DDSs Containing Endemic Helichrysum pamphylicum P.H. Davis & Kupicha Methanolic Extract.

Numerous pharmaceutical applications for chitosan, a polysaccharide made from the shells of crustaceans by deacetylating chitin that occurs naturally, are currently being researched. Chitosan, a natural polymer, is successfully used to prepare many drug-carrier systems, such as gel, film, nanoparticle, and wound dressing. Preparing chitosan gels without external crosslinkers is less toxic and environmentally friendly. Chitosan-based gels containing Helichrysum pamphylicum P.H. Davis & Kupicha methanolic extract (HP) were produced successfully. The F9-HP coded gel prepared with high molecular weight chitosan was chosen as the optimum formulation in terms of pH and rheological properties. The amount of HP was found to be 98.83% ± 0.19 in the F9-HP coded formulation. The HP release from the F9-HP coded formula was determined to be slower and 9 hours prolonged release compared to pure HP. It was determined that HP release from F9-HP coded formulation with the DDSolver program was by anomalous (non-fickian) diffusion mechanism. The F9-HP coded formulation significantly showed DPPH free radical scavenger, ABTS•+ cation decolorizing and metal chelating antioxidant activity while weakly reducing antioxidant potential. According to the HET-CAM scores, strong anti-inflammatory activity was obtained by the F9-HP coded gel at a dose of 20 μg.embryo-1 (p<0.05 compared with SDS). In conclusion, it can be said that chitosan-based gels containing HP, which can be used in both antioxidant and anti-inflammatory treatment, were successfully formulated and characterized.

Calcium silicate‐reinforced pH‐sensitive alginate‐gellan gum composite hydrogels for prolonged drug delivery

AbstractThis study disclosed the synthesis and characterization of externally and/or internally crosslinked alginate‐gellan gum composite interpenetrating polymer networks (IPN) and IPN hydrogel microspheres for controlled delivery of gliclazid. The internal cross‐linking of the polymer sol was accomplished via slow release of Ca2+ ions from calcium silicate in presence of gluconic acid d‐lactone. The microspheres had spherical shape with smooth surface morphology. The IPN or composite IPN hydrogel microspheres had drug entrapment efficiency of 70%–76%. Incorporation of gellan gum or gellan gum/calcium silicate in the alginate sol sustained the release of drug in simulated gastrointestinal fluids over 12 h without any sign of particle disintegration. Inclusion of calcium silicate in alginate gels was ineffective in controlling drug release under simulated gastrointestinal milieu. The drug release obeyed anomalous diffusion mechanism after inclusion of gellan gum or gellan gum‐calcium silicate in the alginate gel microspheres. Fourier‐transform infrared (FTIR) spectroscopy and zeta analysis confirmed absence of drug‐polymer chemical interaction. The thermal and x‐ray diffraction analyses suggested that the drug transformed into amorphous state after incorporation into composite hydrogel system. Hence, it may be advantageous to combine internal and external gelation procedures for creating composite IPN or IPN hydrogel microspheres for avoiding burst effect of alginate microspheres and managing desired drug release patterns in vitro.

On the mechanism of anomalous phenomena in current-carrying magnetized plasma

The explanation of the mechanisms of anomalous resistance and diffusion of plasma, as well as the generation of fast particles, is given from a unified position on the basis of experimental results obtained in plasma in a magnetically isolated diode of an electron accelerator with a microsecond pulse duration. It is shown that oscillations of the potential and current in plasma with current occur by charge separation and the formation of electric domains with a strong field. Electric domains are generated by means of runaway electrons resulting from the redistribution of the current density and its channelling in the current-carrying plasma. An increase in plasma resistance occurs due to a decrease in the number of electrons in the current-conducting state, since some of the plasma electrons pass into layers of excess negative charge of electric domains. The speed of movement of electrons in the composition of the electric domain is much lower than the velocity of electrons in the conducting state. The nucleation of domains is accompanied by microwave emission. Quasi-neutrals in whole electrical domains are injected into the region of the anode wall. The destruction of domains leads to the appearance of plasma channels between the anode and cathode plasma. The transverse electromagnetic waves generated during the nucleation of domains capture charged particles and inject them in a direction that is perpendicular to the insulating longitudinal magnetic field. Plasma turbulence occurs due to charge separation and the generation of electrical domains that create channels between the plasma and the chamber wall, as well as generating fluxes of fast particles.

Nanoparticles loaded with procyanidin B2-3′-O-gallate from grape seed: preparation, characterization and antioxidant activity

The aim of this study was to prepare nanoparticles of grape seed procyanidin B2-3′-O-gallate by chitosan-sodium alginate. The encapsulation system was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC), and its biological activity was analyzed by cell-level antioxidant capacity. The results showed that the particle size of nano-carrier was 160~201nm, the B2-3′-O-gallate was well embedded, and the encapsulation efficiency of B2-3′-O-gallate was 93.5%. In vitro digestion experiments suggested that the release of B2-3′-O-gallate was significantly controlled by chitosan-sodium alginate nano-system through anomalous diffusion mechanism, and at about 72-78% of B2-3′-O-gallate was retained under gastrointestinal (GI) condition. Besides, the cytotoxicity results expressed that B2-3′-O-gallate chitosan nanoparticles had obvious protective effect on human HepG2 cells induced by hydrogen peroxide. This work provides a promising way to control the delivery and enhances the biological activity of galloylated procyanidins – one of the most important group of bioactive polyphenols of the grape pomace.

Ascendancy of pH‐irresponsive Moi gum in the design of modified xanthan gum semi‐interpenetrating network hydrogels for monitoring diabetes

AbstractThis investigation used Moi gum to develop semi‐interpenetrating polymer network (IPN) hydrogel particles with carboxymethyl xanthan gum in aqueous environment using aluminum chloride as crosslinker. The semi‐IPN hydrogel systems had &gt;90% of drug entrapment efficiency. Increase in Moi gum concentration from 33.33% to 66.66% reduced swelling of semi‐IPN hydrogel particles by 17.6% and 23.3% in pH 1.2 and pH 6.8, respectively in 2 h. The semi‐IPN hydrogel particles made up of 66.66% Moi gum released 94.8% of drug in 8 h. The modified xanthan gum alone however released about 98% drug in 3 h in simulated gastrointestinal pH. Irrespective of pH, the drug release followed an anomalous diffusion mechanism. FTIR analysis did not reveal any drug‐polymer interaction. The thermal and x‐ray diffraction investigations suggested amorphous state of drug in semi‐IPN hydrogel system. Moreover, the hydrogel systems demonstrated more than 90% Caco‐2 cell viability which supported the non‐toxic nature of the hydrogel system. Preclinical experiments on male albino rats showed that the semi‐IPN hydrogel systems could allow monitoring of anti‐diabetic efficacy over 8 h. Overall, a suitable combination of negatively charged and neutral polysaccharides appeared promising in developing semi‐IPN hydrogel particles, which could tailor the drug delivery performance, especially the drug release process and preclinical anti‐diabetic activity.

Studies on Jackfruit-Okra Mucilage-Based Curcumin Mucoadhesive Tablet for Colon Targeted Delivery.

The present work investigates a blend of jack fruit mucilage (JFM) and okra mucilage (OKM) as promising mucoadhesive carriers for colon-specific delivery of a curcumin (CMN)-loaded mucoadhesive tablet (CMT) formulation. Formulation optimization was performed using central composite design (CCD) to further decipher the effect of varying proportions of the mucoadhesive carriers JFM and OKG on response factors such as drug release (% DR) and mucoadhesive strength (MA). The optimized formulation CMT (F14) demonstrated a favorable 54.35% in vitro release of CMN in 12 h with release kinetics resulting from a zero-order anomalous diffusion mechanism and MA of 34.1733 ± 1.26 g. Accelerated stability testing of CMT (F14) confirmed a shelf life of about 4.7 years. In vivo drug targeting studies performed using rabbit models in order to observe transit behavior (colon-specific delivery) of the dosage form were assessed by fluoroscopic images of the GI tract. Taking the results together, the results confirm that the combination of JFM and OKM could be exploited as an ideal mucoadhesive carrier for effective delivery of macromolecules to the colon.

Lornoxicam-Loaded Chitosan-Decorated Nanoemulsion: Preparation and In Vitro Evaluation for Enhanced Transdermal Delivery.

Nanoemulsions are promising drug delivery systems for the administration of poorly soluble drugs like lornoxicam (LRX) by oral or parenteral routes. Such formulations work perfectly for transdermal delivery of lornoxicam-type drugs. It has also been established that formulating such a delivery system is highly dependent on the presence, type, and concentration of excipients taking part in the formulation. The inherent characteristics of nanoemulsion (NE), i.e., smaller globule size and excipient nature, facilitate the drug’s passage through skin. The current study was aimed at the development of an NE-based formulation of LRX to improve the drug solubility in vitro as well as to enhance drug skin permeation to promote therapeutic outcome in appropriate time. Spontaneous self-emulsification technique was utilized to develop optimized LRX-encapsulated NE-based formulations. ATR-FTIR spectra of the pure drug and various formulations did not show any interaction between the drug and various formulation excipients showing compatibility. Globule size for stable formulations ranged between 63–168 nm. These formulations were characterized for viscosity, surface tension, pH, drug encapsulation efficiency, in vitro drug release, and drug skin permeation studies. Chitosan-decorated optimized NE formulation of LRX showed about 58.82% cumulative drug release, showing an anomalous non-Fickian diffusion mechanism of drug release. Drug encapsulation efficiency, in vitro drug release, and skin permeation studies exhibited promising results. An appreciable drug entrapment efficiency was exhibited by optimized NE formulations LRX-6, 71.91 ± 3.17% and C-LRX, 65.25 ± 4.89%. Permeability parameters like enhancement ratio (Er), permeability constant (Kp), and steady state flux (Jss) showed higher values and exhibited good results based on formulation type. The selected promising formulation type “LRX-6” showed significantly different results as compared to other formulations (LRX-4, 5, and 7). The skin permeation property of the LRX-6 formulation was compared to similar chitosan-based formulations and was found to have better skin permeation results than chitosan-based formulations. This study clearly exhibited that an LRX-containing NE-based formulation can be formulated to form a stable drug delivery system. Such formulations are promising in terms of physicochemical characteristics, improved solubility, and high skin permeation potential.

Silica hydrogel composites as a platform for soft drug formulations and cosmetic compositions

In this work, silica hydrogels are considered as potential basis for the development of new soft drug formulations and cosmetic products. For this purpose, the hydrogel drug-silica composites having pH ∼7 were synthesized by two-step sol-gel method under different synthesis conditions (concentration of acidic catalyst, addition of co-solvent (DMSO), drug loading). Lipoamide, a powerful antioxidant, was used as the drug. Since biomedical functionality of the hydrogel materials is largely determined by their mechanical properties, response of the hydrogels to deformation under compression, tension and shear was measured, and their thixotropic behavior was also studied. The release kinetics of the drug from the hydrogel composites was investigated in vitro. It was shown that the synthesis conditions influenced significantly on the indicated properties of the synthesized hydrogels. The compression Young's moduli and the thixotropic indexes decreased with increasing catalyst concentration and drug loading due to the destabilizing effect of these factors on microstructure of the hydrogels. However, DMSO promoted improvement of the mechanical properties of the hydrogels. The tensile properties of the hydrogels were very low. It was found that the drug release from the hydrogel composites followed zero order kinetic for two days due to mechanism of anomalous diffusion. The drug release from the hydrogel composites prepared using the highest catalyst concentration and high drug loading is characterized by higher rate constants.

Development of cream to enhance the antifungal activity and reduce the side effects of fluconazole for the treatment of Candida albicans

Abstract The aim of the present study was to formulate a fluconazole cream for the treatment of Candida albicans. The optimized cream formulation was prepared using stearic acid, oleic acid, beeswax and borax. The uniform distribution of the active ingredient fluconazole could be confirmed in all formulated creams. The FC-C-C formulation showed satisfactory spreadability and extrudability. FC-C-C delivered (95.07 ± 15.85)% in only 36 h, and the formulation released the drug by an anomalous diffusion mechanism. The viscosity of FC-C-C was found to be (63.20 ± 0.83) cP. The antifungal study and animal studies confirmed that the prepared formulation is non-irritant and has an enhanced antifungal activity that reduces the side effects of fluconazole. The studies confirm that the prepared formulation may be useful for the treatment of Candida albicans.

Development of a mechanically stable human hair keratin film for cell culture

An easy-to-handle keratin film was successfully fabricated using solely purified hair keratins. Keratin was extracted from human hair by an existing protocol. The extracted keratin was made into a mechanically stable film by solution casting and air-drying at room temperature. The films obtained were characterized for surface morphology, wettability, protein secondary structures, mechanical properties, permeability, and thermal properties. Interestingly, the keratin film showed distinct surface and cross-sectional morphology, and protein secondary structure transformation. In addition, the keratin film exhibited Young’s modulus of 1.05 ± 0.09 GPa when it was dry. In the wet state, the keratin film behaved as viscoelastic material and was highly stretchable at 179 ± 17% strain at break. Permeability test was conducted using 20 kDa-FITC dextran which revealed an anomalous diffusion mechanism through the keratin film. Additionally, the keratin film elicited positive cellular responses by human epidermal keratinocytes (HEKs) in terms of enhanced cell proliferation, viability, keratin 14 expression, and IL-1α secretion, in comparison to collagen I. Taken together, a human hair keratin-based film with its mechanical and thermal stability, and cytocompatibility, presents a promising platform for cell culture applications.

Preparation and Characterization of Curcumin and Epigallocatechin gallate co-loaded polymeric microspheres for Colonic delivery

Curcumin (CURC) is a natural polyphenolic compound obtained from Curcuma longa which shows preventive and therapeutic actions against cancer. Epigallocatechin gallate (EGCG) is a potent phytomolecule obtained from Camellia sinensis, with wide biological activity. The therapeutic effect is limited, owing to poor stability and limited membrane permeability across the intestine. The aim of this study was to develop and evaluate colon-targeted microspheres of CURC and EGCG, using natural polymers. W/O emulsion crosslinking technique was used to prepare microspheres of CURC and EGCG using interpenetrating network (IPN) of Chitosan (CS) and Gum acacia (GA) and glutaraldehyde was used as a crosslinking agent. Prepared microspheres were filled in capsules coated with Eudragit S100. The prepared microspheres were evaluated in vitro for preformulation studies, encapsulation efficiency, micromeritic properties, dissolution studies and stability studies. FTIR and DSC studies had proved that the drug and polymers are compatible. The good flow property of microspheres showed that the microspheres are not aggregated. SEM micrographs of microspheres show a rough and folded surface morphology. The microspheres are spherical and uniform in shape. Formulations showed good encapsulation efficiency. Formulation F1 to F6 showed sustained release of drug for 10 h. The in-vitro drug release of batches was best explained by Higuchi models showing anomalous diffusion mechanism. The coated batch showed better release results. The optimized formulation for a period of 3 month at 40±2°/75 ± 5% RH showed no significant changes. The current approach was helpful to develop polysaccharide based microspheres of CURC and EGCG to enhance colonic drug delivery.

Formulation of floating metronidazole microbeads using Terminalia mantaly gum as polymer

gum was extracted and characterized by material, proximate and pasting properties.Terminalia gum in combination with sodium alginate at varying concentrations(0-80 %w/v) was used in preparing the microbeads by ionotropic gelation using zincchloride as the chelating agent. The microbeads were evaluated using shape,size, swelling, buoyancy, entrapment efficiency, drug release profiles andkinetic modelling. The microbeads were spherical to ovoid in shape with sizesranging from 1093 to 1209.0 µm. The swelling index was 5 to 184 % and itincreased with an increase in gum concentration. Total floating time was highest(175.5 h) for formulations having 20% w/w gum and the least(5.5 h) for those with 80% w/w gum. The entrapment efficiency generally increased with an increase in gumconcentration up to 40% w/w and then reduced. The microbeads showedcontrolled release patterns of metronidazole with the highest t50 of 2260.3. The drug release kineticsfitted the Korsmeyer-Peppas model with a non-Fickian anomalous diffusion mechanism. Terminalia mantaly gum can be furtherdeveloped for use as a co-polymer in the formulation of floating metronidazolemicrobeads.

Numerical simulation of a two‐compartmental fractional model in pharmacokinetics and parameters estimation

Compartmental model is the classic and widely used approach in pharmacokinetics. Recently, fractional calculus is introduced to describe the time course of drugs in human body which follow the anomalous diffusion mechanism. To consider the different fractional order transmission process, the two‐compartmental fractional model has been proposed and studied. And it will be of great significance to find out a simple and efficient numerical method to solve the model and estimate model parameters. This work investigates two numerical methods of the two‐compartmental fractional model using finite difference schemes, which are based on the shifted Grünwald–Letnikov approximate formula and L1 formula, respectively. The hybrid Nelder–Mead simplex search and particle swarm optimization, denoted as NMSS–PSO, is provided to estimate the fractional model parameters. Comparison between the numerical solution and the solution by the numerical inverse Laplace transform method establishes the validity of the developed numerical algorithms. Then the influence of the order of fractional derivative on the drug amount in human body is also discussed. Finally, the two‐compartmental fractional model is applied to fit the amiodarone pharmacokinetics data based on the NMSS–PSO algorithms. This work will be of importance for the development of fractional pharmacokinetics.

Analysis of the swelling kinetic in hydrogels gelled by radiation and by thermal cycling

Hydrogels are cross-linked polymer networks, which are of interest in biomedical applications such as drug delivery system. To achieve successful results in this kind of application it is essential to understand the diffusion mechanisms which are generated in the hydrogel during the swelling process. For this reason, this work consists in carrying out an analysis of the swelling kinetics in hydrogels elaborated through gamma radiation and the combination of gamma radiation with thermal cycling processes. The hydrogels were synthesized using biocompatible polymers irradiating their solution at different doses. A swelling test was performed and the diffusion coefficient and the diffusional exponent were calculated, making an analysis of the kind of diffusion mechanism in the hydrogel matrix. This test showed that the higher radiation absorbed used to get the gels, the lower the swelling percentage, as well as the diffusion coefficient of the water molecules in the hydrogel. The results of the kinetic analysis showed an anomalous diffusion mechanism for the gels obtained at 25 kGy. For those gels of 30 kGy, the diffusion was Fickian. Finally since those gels of 35 kGy was not possible to classify it according to the Fick's law of diffusion. Furthermore, we could observe that the hydrogels that had been obtained by thermal cycling and by irradiation had higher swelling percentages compared to those that were only cross-linked by irradiation. This analysis allowed us to understand the intrinsic behavior of the polymer / solvent mesh system at different doses and under two different crosslinking conditions.

Hydroxyapatite as a Potential Nanofiller in Technologically Useful Chlorinated Acrylonitrile Butadiene Rubber

This paper investigates the effect of hydroxyapatite nanoparticles (HA) on the cure characteristics, tensile and tear strength, elongation at break, hardness, abrasion resistance, heat build-up, resilience, glass transition temperature, oil resistance, alternating current (AC) conductivity and transport properties of chlorinated nitrile rubber (Cl-NBR). The maximum and minimum torque values were increased whereas the cure time values were decreased with the HA content in the Cl-NBR. The uniform dispersion of HA in Cl-NBR was obtained from scanning electron microscopy (SEM) and X-ray diffraction (XRD). Differential scanning calorimetry (DSC) showed the increased glass transition temperature of Cl-NBR with the addition of HA particles. Mechanical properties, conductivity and oil resistance of the composites were greatly increased with the loading of hydroxyapatite. Diffusion results were explained in terms of the loading of nanoparticles and size of the penetrant molecules. Arrhenius and thermodynamic parameters for the diffusion process have been estimated and an anomalous diffusion mechanism was observed.

Analytic description of anomalous diffusion in heterogeneous environments: Fokker-Planck equation without fractional derivatives.

This article presents a one-dimensional model of diffusion in a heterogeneous environment, which qualitatively reflects the transport properties of a polymeric membrane with carbon nanotube areas. We derive the Fokker-Planck equation from a system of stochastic equations using a diffusion regime in polymers and a ballistic diffusion regime in nanotube areas. We demonstrate how the probability density function changes in the presence of nanotubes. The mean-square displacement of nonlinear time dependence is observed, indicating anomalous diffusion. This model explains the mechanism of anomalous diffusion in a ballistic-diffusion regime. Our approach does not suppose any type of distribution and does not use a fractional differentiate apparatus.

Drying characteristics of maize grain in solar bubble dryer

AbstractA newly designed solar bubble dryer was used to study the drying behavior of freshly harvested maize grain. The performance of the dryer was tested at sample loads of 10.87 kg/m2 (thin layer), 16.3 kg/m2 (medium layer), and 21.74 kg/m2 (thick layer) under two mixing conditions, 2 and 3 hr intervals. BH‐540 and BH‐660 maize varieties at 22–29% (w.b.) moisture content were used. A temperature rise of about 30°C was recorded in the dryer with respect to the ambient air. The required drying time was highly dependent on sample load. About 24 hr were required to dry the grain to 13% (w.b.) moisture in thin layer compared to 39 hr in thick layer. More frequent mixing of grain (2 hr interval) shortened the drying time by 5–17%. The thin layer experimental data were fitted to drying models and the goodness fit of each model was evaluated using R2, sum square error, and root mean square error. The Verma et al. and diffusion approach models gave better prediction for both varieties and mixing conditions. Fick's second law and anomalous diffusion models were considered for effective diffusion (Deff) calculation. The anomalous diffusion mechanism fitted the experimental data better than Fick's second law and showed a subdiffusive behavior (α &lt; 1).Practical ApplicationsIn developing countries, there is a high percentage of postharvest loss of grains due to traditional/open sun drying method after maturity stage of the plant. Solar drying is a good option to reduce the loss and to produce good quality grains after harvesting. In this study, the performance of newly designed solar bubble dryer and a thin‐layer drying mathematical modeling for freshly harvested maize grain is presented. This study will be useful not only for small holder farmers, but also for all agricultural cooperatives in giving a sustainable and low‐cost grain drying technology. It will be important to produce safe grain products for consumers and for different food industries. In addition, it may be helpful in the design, modeling, and performance assessment of solar dryers and can be used as a reference for solar drying applications for grain crops.

Atenolol-releasing buccal patches made of Dillenia indica L. fruit gum: preparation and ex vivo evaluations

The objective of present research deals with the utility of extracted dillenia fruit gum (DG) as pharmaceutical excipient in the formulation of buccal patches containing atenolol (for the use in the treatment of hypertension). The atenolol-releasing buccal patches having a mucoadhesive polymeric layer of extracted DG-hydroxypropyl methylcellulose (HPMC K4M) and a drug-free backing layer of ethyl cellulose (1%) were prepared through the solvent-casting process. Various physicochemical parameters such as drug content, average weight, thickness, folding endurance and moisture content of all these buccal patches were found satisfactory. Ex vivo buccoadhesion was also found satisfactory. Ex vivo drug permeation across the excised porcine buccal mucosal membrane demonstrated the atenolol permeation over 12 h, which obeyed the first-order model (R2 = 0.9858–0.9967) with non-Fickian (anomalous) diffusion mechanism (n = 0.72–0.75). These buccal patches were also characterized by SEM and FTIR spectroscopy. These atenolol-releasing buccal patches can be used in the treatment of hypertension and angina pectoris bypassing the extensive hepatic first-pass metabolism.