Nanocurcumin-Based Sugar-Free Formulation: Development and Impact on Diabetes and Oxidative Stress Reduction.

The objective of this study is the development of innovative nanocurcumin-based formulations designed for the treatment and prevention of oxidative stress and diabetes. Nanocurcumin was obtained through a micronization process and subsequently encapsulated within biopolymers derived from corn starch and fenugreek mucilage, achieving encapsulation rates of 75% and 85%, respectively. Subsequently, the encapsulated nanocurcumin was utilized in the formulation of sugar-free syrups based on Stevia rebaudiana Bertoni. The stability of the resulting formulations was assessed by monitoring particle size distribution and zeta potential over a 25-day period. Dynamic light scattering (DLS) revealed a particle size of 119.9 nm for the fenugreek mucilage-based syrup (CURF) and 117 nm for the corn starch-based syrup (CURA), with polydispersity indices PDIs of 0.509 and 0.495, respectively. The dissolution rates of the encapsulated nanocurcumin were significantly enhanced, showing a 67% improvement in CURA and a 70% enhancement in CURF compared with crude curcumin (12.82%). Both formulations demonstrated excellent antioxidant activity, as evidenced by polyphenol quantification using the 2.2-diphenyl 1-pycrilhydrazyl (DPPH) assay. In the evaluation of antidiabetic activity conducted on Wistar rats, a substantial reduction in fasting blood sugar levels from 392 to 187 mg/mL was observed. The antioxidant properties of CURF in reducing oxidative stress were clearly demonstrated by a macroscopic observation of the rats' livers, including their color and appearance.

Experimental Analysis and Neural Network Modeling of the Rheological Behavior of Xanthan Gum and Its Derivatives.

The main objective of this study was to create a mathematical tool that could be used with experimental data to predict the rheological flow behavior of functionalized xanthan gum according to the types of chemical groups grafted onto its backbone. Different rheological and physicochemical analyses were applied to assess six derivatives synthesized via the etherification of xanthan gum by hydrophobic benzylation with benzyl chloride and carboxymethylation with monochloroacetic acid at three (regent/polymer) ratios R equal to 2.4 and 6. Results from the FTIR study verified that xanthan gum had been modified. The degree of substitution (DS) values varying between 0.2 and 2.9 for carboxymethylxanthan gum derivatives were found to be higher than that of hydrophobically modified benzyl xanthan gum for which the DS ranged from 0.5 to 1. The molecular weights of all the derivatives were found to be less than that of xanthan gum for the two types of derivatives, decreasing further as the degree of substitution (DS) increased. However, the benzyl xanthan gum derivatives presented higher molecular weights varying between 1,373,146 (g/mol) and 1,262,227 (g/mol) than carboxymethylxanthan gum derivatives (1,326,722-1,015,544) (g/mol). A shear-thinning behavior was observed in the derivatives, and the derivatives' viscosity was found to decrease with increasing DS. The second objective of this research was to create an ANN model to predict one of the rheological properties (the apparent viscosity). The significance of the ANN model (R2 = 0.99998 and MSE = 5.95 × 10-3) was validated by comparing experimental results with the predicted ones. The results showed that the model was an efficient tool for predicting rheological flow behavior.

Formulation and Evaluation of Xanthan Gum Microspheres for the Sustained Release of Metformin Hydrochloride.

This work aimed to formulate xanthan gum microspheres for the encapsulation of metformin hydrochloride, according to the process of ionotropic gelation. The obtained microparticles, based on various fractions of xanthan gum (0.5-1.25), were subjected to different physico-chemical tests and a drug release study. Microspheres with an average size varying between 110.96 µm and 208.27 µm were obtained. Encapsulation efficiency reached 93.11% at a 1.25% biopolymer concentration. The swelling study showed a swelling rate reaching 29.8% in the gastric medium (pH 1.2) and 360% in the intestinal medium (pH 6.8). The drug release studies showed complete metformin hydrochloride release from the beads, especially those prepared from xanthan gum at the concentration of 1.25%, in intestinal medium at 90.00% after 6 h. However, limited and insignificant drug release was observed within the gastric medium (32.50%). The dissolution profiles showed sustained release kinetics.

Synthesis and physicochemical evaluation of octenylsuccinated kappa-carrageenan: Conventional versus microwave heating.

This research reported on the synthesis and the evaluation of new octenyl succinate (OS) kappa-carrageenan (KC) esterified derivatives (KC-OS). Two derivatives were synthesized using microwave (KC-OSMM) and conventional heating (KC-OSCM). The FT-IR and 1H NMR demonstrated the KC-OS esters formation with a higher degree of substitution for KC-OSMM (0.85) than KC-OSCM (0.62). The SEM testing showed the non-deteriorated morphology of KC after modification. The amphiphilic properties and surface activity of KC-OSs investigated by the conductivity method confirmed the formation of self-assembled aggregates beyond a critical aggregation concentration of 0.08% for KC-OSMM and 0.12% for KC-OSCM. Stable oil-in-water emulsions were formulated based on KC-OSs at the concentrations of 0.75% and 1%. Lower globule sizes were observed for KC-OSMM emulsions at 0.75% (12.30 µm) and 1% (08.86 µm), compared to KC-OSCM at 0.75% (32.75 µm) and 1% (19.6 µm). All results demonstrated that microwave synthesis resulted in obtaining novel derivatives with superior properties.

Implementation and in vitro characterization of calcium-free in situ gelling oral reconstituted suspension for potential overweight treatment.

In this work, oral granules that were easily dissolved in aqueous dispersion, were prepared. These oral suspensions were formulated with sodium alginate (AlgNa), chitosan (CHI) and sodium carboxymethylcellulose (CMC Na). The gels were formulated by pouring the suspensions into 150 ml of simulated gastric fluid (SGF) pH 1.2 at 37° C. The in-situ gelling mechanism was based on the ionization states of the three biopolymers as a function of the pH of the medium. Fourier transform infrared analysis of gels confirmed the interactions between alginate and chitosan. According to the scanning electron microscopy analysis, the gels were characterized by a firm and homogeneous structure. The obtained values of the elastic storage modulus, G', varied between 10 1 and 10 7 Pa. The eliminated volume of the unabsorbed liquid by the gels fluctuated between 25% and 55% of the total liquid volume. The quality of the gels was improved when a maximum concentration of alginate ( 4 g / 100 ml ) , a minimum concentration of chitosan ( 0.5 g / 100 ml ) and a maximum amount of carboxymethylcellulose ( 4 g / 100 ml ) were used. The value of their elastic modulus, G' was around 10 5 Pa and the residual unabsorbed volume of the liquid was 25% of the total liquid volume. According to the obtained results, the prepared gels could induce a feeling of fullness by stimulating the gastric distension and they could potentially be applied as anti-obesity medication.

Synthesis, characterization and potential application of hydrophobically modified carrageenan derivatives as pharmaceutical excipients.

New amphiphilic derivatives of kappa-carrageenan (KC) were synthesized by hydrophobic modification with octyl chloride. Two different methods based on microwave and conventional heating were used. All KC derivatives (KCRs) were characterized by different techniques. The FT-IR and 1HNMR studies demonstrated that the octyl groups were effectively grafted onto KC backbone and confirmed that the derivative KCRMM, obtained by microwave heating, presented a higher degree of substitution (DS = 0.77) compared to KCRCM (0.45). The amphiphilic character investigation also revealed that KCRMM exhibited a lower critical aggregation concentration (CAC) value of 0.13% w/v than KCRCM (0.15%). Furthermore, KCRs greatly improved the stability of oil/water emulsions as the droplet size decreased with increasing DS. Unlike the conventional heating method, novel derivatives with a higher DS, greater amphiphilic character, and an improved emulsifying power were obtained by microwave-assisted synthesis. These derivatives could potentially be used in food, cosmetics, or as excipients in pharmaceutics.

Artificial neural network for modeling formulation and drug permeation of topical patches containing diclofenac sodium.

In this work, topical matrix patches of diclofenac sodium (DS) were formulated by the solvent casting method using different ratios of chitosan (CTS) and kappa carrageenan (KC). Propylene glycol and tween 80 were used as a plasticizer and permeation enhancer, respectively. The drug matrix film was cast on a polyvinyl alcohol backing membrane. All the patches were evaluated for their physicochemical characteristics (thickness, folding endurance, flatness, drug content, tensile strength, bioadhesion, moisture content, and moisture uptake), along with their in vitro release and in vitro skin permeation studies. Franz diffusion cells were used to conduct the in vitro permeation studies. The artificial neural network (ANN) model was applied to simultaneously predict the DS release and the ex vitro skin permeation kinetics. The formulated patches showed good physicochemical properties. Out of all the studied patches, F6 presented sustained permeation in 32 h and was selected as the best formulation. The ANN model accurately predicted both the kinetic release and the skin permeability of DS from each formulation. This performance was demonstrated by the obtained R2 = 0.9994 and R2 = 0.9798 for release and permeation kinetics modeling, respectively, with root mean square error (RMSE) = 3.46 × 10-5.

Synthesis, characterization and evaluation of deacetylated xanthan derivatives as new excipients in the formulation of chitosan-based polyelectrolytes for the sustained release of tramadol.

This paper addressed the application of deacetylated xanthan (XGDS) and chitosan (CTS) as a mixture blend forming hydrophilic matrices for Tramadol (TD) sustained release tablets. XGDSs derivatives were obtained by alkaline treatment of xanthan gum (XG) with various degrees of deacetylation (DD). The obtained products were characterized in terms of structural, thermal and physicochemical properties. Different tablet formulations containing CTS/XGDSs were prepared by direct compression method and compared to CTS/XG tablets. Flow properties of powder mixtures and pharmaceutical characteristics were evaluated. The dissolution test of TD was realized under simulated gastric and intestinal conditions to achieve drug release more than 24 h. All developed tablets were found conforming to standard evaluation tests. It was shown that CTS/XGDSs matrices ensure a slower release of TD in comparison with CTS/XG based formulations. Meanwhile, increasing DD resulted in a decrease of drug release. In addition, TD release from XGDS matrices was faster at pH (6.8) than at acidic pH (1.2). The matrix tablets based on CTS/XGDS4 (DD = 98.08%) were selected as the best candidates compared to the other systems in prolonging drug release. The optimal formulation was found to release 99.99% of TD after 24 h following a non-Fickian type.

Neuro-fuzzy modeling of ibuprofen-sustained release from tablets based on different cellulose derivatives.

In the present study, we investigated the drug release behavior from cellulose derivative (CD) matrices in the oral form of tablets. We used the adaptive neural-fuzzy inference system (ANFIS) to predict the best formulation parameters to get the perfect sustained drug delivery using ibuprofen (IB) as a model drug. The different formulations were prepared with different CDs, namely CMC, HEC, HPC, HPMC, and MC. The amount of the active ingredient varied between 20 and 50%. The flow properties of the powder mixtures were evaluated for their angle of repose, compressibility index, and Hausner ratio, while the tablets were evaluated for weight uniformity, hardness, friability, drug content, disintegration time, and release ratio. All tablet formulations presented acceptable pharmacotechnical properties. In general, the results showed that the drug release rate increases with an increase in the loaded drug. Kinetic studies using the Korsmeyer-Peppas equation showed that different drug release mechanisms were involved in controlling the drug dissolution from tablets. The drug release mechanism was influenced by the gel layer strength of the CDs formed in the dissolution medium. The mean dissolution time (MDT) was determined and the highest MDT value was obtained for the HPMC formulations. Moreover, HPMC exhibited release profiles adequate for sustained release formulations for over 14 h. The intelligent model based on the experimental data was used to predict the effect of the polymer's nature, the amount of the active ingredient, and the kinetic release profile and rate (R2 = 0.9999 and RMSE = 5.7 × 10-3). The ANFIS model developed in this work could accurately model the relationship between IB release behavior and tablet formulation parameters. The proposed model was able to successfully describe this phenomenon and can be considered an efficient tool with predictive capabilities that is useful for the designing and testing of new dosage systems based on polymers.

Design of antihistaminic transdermal films based on alginate-chitosan polyelectrolyte complexes: characterization and permeation studies.

The purpose of this study was to develop suitable matrix-type transdermal drug delivery systems of Ketotifen fumarate (KF) as antiasthmatic drugs. Chitosan-alginate polyelectrolyte complex (PEC) films were used as drug release regulators for KF. Antihistaminic films with variable PEC compositions were prepared using different ratios of chitosan (CTS) to sodium alginate (ALG). Propylene glycol (PG) was used as plasticizer; Tween 80 (T80) and Span 20 (S20) were used as permeability enhancers. Nine formulations were obtained by film casting method and characterized in terms of weight uniformity, thickness, folding endurance, moisture lost, and moisture absorption. In addition, drug release and permeation through rat abdominal skin mounted in Franz cell were investigated. All formulations were found to be suitable in terms of physicochemical characteristics, and there was no significant interaction between the used drug and polymers. It was noticed that when T20 is used as permeation enhancer, a satisfactory drug release pattern was found where 99.88% of drug was released and an amount of 2.121 mg/cm2 of KF was permeated after 24 h. For the optimal formulation, a permeability coefficient of 14.00 ± 0.001 cm h-1 and a latency time of 0.35 ± 0.02 h were found. The in-vitro analysis showed controlled release profile which was fitted by Korsmeyer-Peppas model (R2 = 0.998). The obtained results suggested that new controlled release transdermal formulations of asthmatic drugs could be suitably designed as an alternative to the common forms.

Synthesis and evaluation of the structural and physicochemical properties of carboxymethyl pregelatinized starch as a pharmaceutical excipient.

A pregelatinized starch (PGS) was derivatized with sodium chloroacetate (SCA) in alcoholic medium under alkaline condition to produce carboxymethyl pregelatinized starch (CMPGS) with various degrees of substitution (DS). Influence of the molar ratio of SCA to the glucopyranose units (SCA/GU), reaction time, temperature and the amount of sodium hydroxide on the degree of substitution (DS) and the reaction efficiency (RE) was studied. An optimal concentration of 30% of NaOH, for a reaction time of 1 h at 50 °C and molar ratio (SCA/GU) equal to 1.0, yielded an optimal DS of 0.55 and a RE of 55%. SEM micrographs revealed that the carboxymethylation assigned the structural arrangement of CMPGS and caused the granular disintegration. Wide angle diffraction X-ray (XRD) showed that the crystallinity of starch was obviously varied after carboxymethylation. New bands in FTIR spectra at 1417 and 1603 cm(-1) indicated the presence of carboxymethyl groups. The solubility and viscosity of CMPGS increased with an increase in the degree of modification. In order to investigate the influence of DS on physical and drug release properties, CMPGS obtained with DS in the range of 0.12-0.55 was evaluated as tablet excipient for sustained drug release. Dissolution tests performed in phosphate buffer (pH 6.8), with Ibuprofen as drug model (25% loading) showed that CMPGS seems suitable to be used as sustained release excipient since the drug release was driven over a period up to 8 h. The in vitro release kinetics studies revealed that all formulations fit well with Korsmeyer-Peppas model and the mechanism of drug release is non-Fickian diffusion.