Optimization of Ultrasonic-Assisted Extraction of Phenolic Compounds and Antioxidant Activity from Araticum Peel Using Response Surface Methodology.

The peel represents a significant portion of the araticum fruit (about 40%), which becomes waste after its consumption or processing. Previous studies have shown that the araticum peel is rich in phenolic compounds; however, little is known about the ideal conditions for recovering these compounds. Therefore, response surface methodology, using a central composite rotatable design, was employed to optimize the extraction process to maximize the total phenolic compounds (TPCs) and enhance the Trolox equivalent antioxidant capacity (TEAC) from araticum peel. The variables optimized were ethanol concentration (EC; 20-80%, v/v), extraction time (ET; 5-45 min), and solid-solvent ratio (SSR; 10-100 mg/mL). Additionally, condensed tannins, antioxidant capacity against synthetic free radicals (TEAC and FRAP) and reactive oxygen species (ROS), and the phenolic compounds profile, were evaluated. Optimum extraction conditions were 50% (v/v) ethanol concentration, 5 min of extraction time, and 10 mg/mL solid-solvent ratio. Under these conditions, experimental TPCs and TEAC values were 70.16 mg GAE/g dw and 667.22 µmol TE/g dw, respectively, comparable with predicted models (68.47 mg GAE/g dw for TPCs and 677.04 µmol TE/g dw for TEAC). A high condensed tannins content (76.49 mg CE/g dw) was also observed and 12 phenolic compounds were identified, predominantly flavonoids (97.77%), including procyanidin B2, epicatechin, and catechin as the major compounds. Moreover, a potent antioxidant activity was observed against synthetic free radicals and ROS, especially in scavenging peroxyl and hydroxyl radicals. From this study, we obtained the ideal conditions for recovering phenolic compounds from araticum peel using a simple, fast, sustainable, and effective method, offering a promising opportunity for the management of this plant byproduct.

A practical and eco-friendly method for the determination of polycyclic aromatic hydrocarbons in açaí-based food products by vacuum-assisted sorbent extraction coupled to gas chromatography-mass spectrometry.

For the first time, a method for the simultaneous analysis of fifteen polycyclic aromatic hydrocarbons (PAHs), including light and heavy PAHs, in açaí-based food products (AFPs) was developed using vacuum-assisted sorbent extraction (VASE) combined with gas chromatography-mass spectrometry (GC-MS). The method requires no organic solvents and is amenable to full automation. To achieve optimal analytical extraction conditions, VASE parameters including stirring rate, extraction time, desorption temperature, desorption time, preheat time, and preheat temperature were optimized using sequential multivariate optimization. The method was validated and yielded limits of quantification below 1 µg kg-1 for all analytes, with recoveries ranging from 65 % to 112 % and good precision (≤11 % relative standard deviation). Additionally, the greenness and practical aspects of the method were investigated using the Green Analytical Procedure Index (GAPI), eco-scale, and the Blue Applicability Grade Index (BAGI), respectively. The VASE-GC-MS approach is suitable for routine analysis and exhibits characteristics of a green analytical method. No PAHs were detected above the limits of detection in thirty samples of AFPs.

Ultrasound-assisted extraction and concentration of phenolic compounds from jabuticaba sabará (Plinia peruviana (Poir.) Govaerts) peel by nanofiltration membrane.

Jabuticaba peel, rich in antioxidants, offering health benefits. In this study, the extraction of phenolic compounds from jabuticaba peel using ultrasound-assisted (UA) and their subsequent concentration by nanofiltration (NF) employing a polyamide 200 Da membrane was evaluated. The UA extractions were conducted using the Central Composite Rotatable Design (CCRD) 22 methodology, with independent variables extraction time (11.55 to 138 min) and temperature (16.87 to 53.3 °C), and fixed variables mass to ethanol solution concentration at pH 1.0 (1:25 g/mL), granulometry (1 mm), and ultrasonic power (52.8 W). The maximum concentrations obtained were 700.94 mg CE/100 g for anthocyanins, 945.21 mg QE/100 g for flavonoids, 133.19 mg GAE/g for phenols, and an antioxidant activity IC50 of 24.36 µg/mL. Key phenolic compounds identified included cyanidin-3-glucoside, delphinidin-3-glucoside, and various acids like syringic and gallic. NF successfully concentrated these compounds, enhancing their yield by up to 45%. UA and NF integrate for sustainable extraction.

Multivariate optimization for extraction of 2-methylimidazole and 4-methylimidazole from açaí-based food products using polymeric ionic liquid-based sorbent coatings in solid-phase microextraction coupled to gas chromatography-mass spectrometry.

In this study, polymeric ionic liquids featuring different functional moieties were applied as sorbent coatings in direct-immersion solid-phase microextraction (DI-SPME) for the extraction of 2-methylimidazole (2-MI) and 4-methylimidazole (4-MI) from açaí-based food products followed by gas chromatography-mass spectrometry (GC-MS) analysis. The analytical method was optimized using a sequential experimental design. Variables used in GC-MS such as desorption time, as well as for SPME-DI, including extraction time, extraction temperature, incubation time of extraction, amount of NaCl in the extract, and stirring rate, were optimized. The fitness-for-purpose of the method was verified by the linearity of matrix-matched calibration curves (R2 ≥ 0.9921), adequate recoveries (81.7-89.7 %), and precision (relative standard deviations ≤11.2 %). The method was applied to twenty-five samples of açaí-based food products. 4-MI was found in four samples whereas 2-MI was not detected above the limit of detection. The method was found to be suitable for quality control analysis.

Application of sequential design for enhanced L-asparaginase synthesis from Ganoderma australe GPC191.

With an increasing demand for L-asparaginase in pharmaceutical and food sectors for its cytostatic and acrylamide-reducing qualities, there's a need to discover novel, highly productive enzyme sources with improved pharmacokinetic profiles. Keeping this in mind, the present study aimed at maximizing the potential of Ganoderma australe GPC191 to produce L-asparaginase by fermentation medium optimization using statistical validation. Of the 11 physicochemical parameters evaluated under submerged fermentation conditions through one-factor-at-a-time approach and Plackett-Burman design, only four parameters (inoculum load, L-asparagine, soybean meal, and initial pH) influenced L-asparaginase production, significantly (p < 0.001). The optimal levels and interaction effects of these on the overall production were further evaluated by the central composite rotatable design of response surface methodology. Post-optimization, 27.34 U/mL was predicted as the maximum activity at pH 7 with 5n inoculum load and 15 g/L each of L-asparagine and soybean meal. Experimental validation yielded an activity of 28.52 U/mL, indicating an overall 18.17-fold increase from the unoptimized stage. To our knowledge, this is the first report signifying the L-asparaginase production aptitude of G. australe with sequential statistical validation using agricultural waste, which can serve as a model to enhance its yields, offering a sustainable and cost-effective solution for industrial application.

Optimization of ultrasound - assisted extraction of phenolic compounds and flavonoids from Hortia oreadica leaf / Optimización de la extracción asistida por ultrasonido de compuestos fenólicos y flavonoides de la hoja de Hortia oreadica

Hortia oreadica is indiscriminated used by people from Cerrado. However, vegetable raw material quality is decisive in obtaining inter mediate and final products. So, this study aimed to establish quality parameters of H. oreadica . For this, we performed the phytochemical screening of H. oreadica leaf and identified the best extractive conditions for phenolic compounds and flavonoids usin g factorial experimental design, varying the alcoholic strength, extraction temperature, and solid/liquid ratio in the ultrasound - assisted extraction method. The optimum extraction condition for phenolic compounds and flavonoids was 60% alcoholic strength, 40°C temperature, and a solid/liquid ratio of 8 mg/m L . Under this setting, the phenolic and flavonoid contents were 0.171 ± 0.002 mg/m L (predicted value = 0.165) and 0.087 ± 0.002 mg/m L (predicted value = 0.084), respectively. The optimized extraction par ameters could be upscaled to develop pharmaceutical drugs or nutraceutical products from this non - traditional plant species using an eco - friendly approach.

Hortia oreadica es utilizada indiscriminadamente por la gente del Cerrado. Sin embargo, la calidad de la materia prima vegetal es determinante en la obtención de productos intermedios y finales. Por lo tanto, este estudio tuvo como objetivo establecer parámetros de calidad de H. oreadica . Para ello, realizamos el tamizaje fitoquímico de la hoja de H. oreadica e identificamos las mejores condiciones extractivas para compuestos fenólicos y flavonoides mediante un diseño experimental factorial, variando el grado alcohólico, la temperatura de extracción y la relación sólido/líquido en el método de extracción asistido por ultrasonido. La condición óptima de extracción para compuestos fenólicos y flavonoides fue de 60% de grado alcohólico, 40°C de t emperatura y una relación sólido/líquido de 8 mg/m L . Bajo esta configuración, los contenidos de fenoles y flavonoides fueron 0,171 ± 0,002 mg/m L (valor previsto = 0,165) y 0,087 ± 0,002 mg/m L (valor previsto = 0,084), respectivamente. Los parámetros de ext racción optimizados podrían ampliarse para desarrollar fármacos o productos nutracéuticos a partir de esta especie de planta no tradicional uti lizando un enfoque ecológico .

Optimizing the effect of ultrasonication and germination on antinutrients and antioxidants of kodo (Paspalum scrobiculatum) and little (Panicum sumatrense) millets.

Kodo (Paspalum scrobiculatum) and little (Panicum sumatrense) millet grains were utilized to minimize their antinutrient content (phytate and tannin) and maximize their antioxidant activity (DPPH) by studying the effect of ultrasonication time, germination time and temperature using central composite rotatable design. Results revealed the optimum conditions for producing ultrasonicated and germinated kodo and little millet flour of the highest antioxidant activity and lowest antinutrient content (phytate and tannin) by using 30 min for ultrasonication, 72 h for germination at 40 °C. Further, a second order model was developed to describe and predict the effect of process variables on antioxidant activity and antinutrient contents. Extended experiments were carried out under the optimized conditions to validate the developed model. The antioxidant activity obtained was 88.46% RSA and 89.06% RSA for kodo and little millet grain flours, respectively whereas antinutrient content for phytate was 0.165 mol/kg and 0.199 mol/kg and for tannin 2.88 mol/kg and 9.51 mol/kg, for kodo and little millet grain flours, respectively. This study provides useful information about the potential utilization of ultrasonicated and germinated kodo and little millet grain flours for the development of functional foods.

Exploration for cobalt/nitrogen-doped catalyst to creatinine degradation via peroxymonosulfate activation: toxicity evaluation, statistical modeling, and mechanisms study.

Developing multifunctional catalysts applied in diversiform modes via advanced oxidation processes (AOPs) is a promising and attractive approach for organic pollution degradation. Herein, a novel hollow bamboo-like structural cobalt/nitrogen-doped carbonized material (CoC/N) was employed as a catalyst for AOPs, in which CoC/N was prepared in situ through calcining a Co-based coordination polymer. When CoC/N was utilized as a peroxymonosulfate (PMS) activator, the catalyst stood out prominent activities for effective CA oxidation. Furthermore, a five-level central composite rotatable design (CCRD) model describing CA decay as a function of PMS concentration, CoC/N dosage, and solution pH value was successfully constructed and engaged to explore the optimal operating conditions. Finally, the possible degradation mechanism of CA in CoC/N-PMS system was proposed by quantum chemistry calculation and LC/MS analysis. This work shed light on the structural morphology of the catalyst and its PMS synergy degradation pathway, which promotes its applications in miscellaneous pollutant degradation. A new Co/N-doped material was used to degrade unconventionality organic pollutant creatinine (CA) for the first time, in which the scientific approaches of five-level central composite rotatable design (CCRD) model, response surface methodology (RSM) and density function theory (DFT) were employed to evaluate the material performance and CA degradation pathway. The toxicity evaluation, statistical modeling and mechanisms study have been investigated meticulously.

Nanoencapsulation of Phenolic Extracts from Native Potato Clones (Solanum tuberosum spp. andigena) by Spray Drying.

Native potato clones grown in Peru contain bioactive compounds beneficial to human health. This study aimed to optimize the spray-drying nanoencapsulation of native potato phenolic extracts utilizing a central composite design and response surface methodology, obtaining the optimal treatment to an inlet temperature of 120 °C and an airflow of 141 L/h in the nano spray dryer B-90, which allowed maximizing the yield of encapsulation, antioxidant capacity (DPPH), encapsulation efficiency (EE), total phenolic compounds, and total flavonoids; on the other hand, it allowed minimizing hygroscopicity, water activity (Aw), and moisture. Instrumental characterization of the nanocapsules was also carried out, observing a gain in lightness, reddening of the color, and spherical nanoparticles of heterogeneous size (133.09-165.13 nm) with a negative ζ potential. Thermal, infrared, and morphological analyses confirmed the encapsulation of the core in the wall materials. Furthermore, an in vitro release study of phenolic compounds in an aqueous solution achieved a maximum value of 9.86 mg GAE/g after 12 h. Finally, the obtained nanocapsules could be used in the food and pharmaceutical industry.

Optimization of glutathione production in Saccharomyces cerevisiae HBSD-W08 using Plackett-Burman and central composite rotatable designs.

BACKGROUND: Glutathione is an important bioactive tripeptide and is widely used in the food, medicine, and cosmetics industries. The aim of this study was to provide an efficient method for producing GSH and to explore its synthesis mechanism. Saccharomyces cerevisiae strain HBSD-W08 was screened for GSH production, and its fermentation medium was optimized using single-factor experiments of the Plackett-Burman and central composite rotatable designs. This method was used to analyze the effects of the presence and concentration of various carbon sources, organic and inorganic nitrogen sources, metal ions, and precursor amino acids on GSH production and catalase, superoxide dismutase, and γ-glutamylcysteine synthetase activity. RESULTS: The three most significant factors affecting GSH production were peptone (optimal concentration [OC]: 2.50 g L- 1), KH2PO4 (OC: 0.13 g L- 1), and glutamic acid (OC: 0.10 g L- 1). GSH productivity of HBSD-W08 was obtained at 3.70 g L- 1 in the optimized medium. The activity of γ-GCS, which is a marker for oxidative stress, was found to be highly positively correlated with GSH production. CONCLUSIONS: This finding revealed an underlying relationship between GSH synthesis and oxidative stress, providing useful information for developing effective GSH fermentation control strategies.

Optimization of a novel vacuum sublimation-rehydration thawing process.

To better guarantee the quality of the thawed meat, maximize the thawing rate, and minimize the system energy consumption, the multiparameter and multi-objective coupling optimizations for the newly proposed vacuum sublimation-rehydration thawing (VSRT) process was conducted. The polynomial nonlinear regression equations of single and comprehensive objectives were established by the central composite rotatable design, and the corresponding test of fitting degree and the analysis of influencing factors order were carried out. Furthermore, the interaction effects of influencing factors were investigated through the response surface methodology and were experimentally validated to obtain the optimal process parameters. The results showed that the established regression equations were in good agreement with the experimental values. For the different objectives, there were great differences in the influence order and interaction of factors. In the sublimation and rehydration stages, there existed an optimal region in the response surface to achieve a better value for the single and comprehensive objectives. When the sublimation time was 19 min, the heating plate temperature was 26°C, the rehydration water volume was 1634 ml, the rehydration water temperature was 29°C, the thawing time was relatively short (1.00 h), and the thawing loss (1.19%), the total color difference (1.02), and the system-specific energy consumption (0.026 kW h/kg) were relatively low. The comprehensive performance of the VSRT system reached the best state. PRACTICAL APPLICATION: The purpose of this work is to make the novel vacuum sublimation-rehydration thawing method not only better guarantee the quality of thawed meat but also maximize the thawing rate and minimize the energy consumption of the system, which can provide a new idea and reference for the development of new high-efficiency thawing equipment.

Optimization of chemical solution concentration and exposure time in the alkaline pretreatment applied to sugarcane bagasse for methane production.

ABSTRACTSugarcane is the most traded crop in the world, with Brazil being the world's largest producer. Sugarcane processing generates up to 28% of sugarcane bagasse (SB) from the entire plant, with only 50% of it used for energy generation. SB is a lignocellulosic biomass that can be converted into biogas. However, the optimization of pretreatment process parameters is essential for its successful scaling up. This study evaluated the effect of mild alkaline pretreatment of SB using NaOH and KOH at concentrations of 1-10% and exposure time of 1-12 hours) on the biochemical methane potential (BMP) under mesophilic temperature. The central composite rotatable design (CCRD) was applied as statistical tool to generate optimal operating pretreatment conditions. The tests were performed in triplicates totalizing 84 batch bottles. The BMP of the untreated SB varied between 297-306 LN CH4 kg VS-1 while the BMP of the pretreated samples with NaOH and KOH were 19% and 20% higher. The optimized conditions were NaOH at 7.7% and KOH at 8.3% KOH for 12 hours. However, the range indicated by the statistical design with CCRD revealed that there was no statistical difference in terms of methane yield when concentrations between 4-10% NaOH and 6-10% KOH during 12 hours were applied, when compared to the specific optimized points. The optimization of the pretreatment parameters demonstrated to be a key-factor to improve the anaerobic digestion of lignocellulosic substrates, leading to a less chemically dependent and more sustainable approach, while allowing a more profitable process.

Optimization of process conditions for effective ohmic heating of greater lizardfish (saurida tumbil) sausage via response surface methodology.

In current research, the optimization of ohmic heating on greater lizardfish (Saurida tumbil) sausage variables was carried out using response surface methodology-central composite design (RSM-CCD). The effect of process variables including voltage gradient (15-60 V/cm), time (1-15 min), and temperature (60-90°C) on the microbial properties, pH, peroxide value, water holding capacity (WHC), and cooking loss of the sausages was evaluated. The results showed that the characteristics of the sausages were dependent on the ohmic heating conditions and these properties can be modulated. As per the results, the voltage gradient and temperature has a significant effect on the total plate count (p < 0.05). The increase in voltage gradient was the most effective on pH (5.63-6.91). The interaction terms of all items had a significant effect (p < 0.05) on the peroxide value of the fish sausages. Higher amount of temperature and process time were resulted in the more cooking loss. Increasing the voltage gradient was more effective on WHC compared to the temperature. Finally, the process was optimized and the optimized condition was achieved by setting the voltage gradient at 30 V/cm, process time at 4 min, and temperature at 66 °C. Also, it was compared with conventional heating. The results were shown that the differences between the mean values of all responses were statistically significant (p < 0.05) except for pH. Therefore, ohmic method was carried out faster, with lower temperature and obtaining the highest WHC and lowest total plate count, peroxide value, cooking loss, and optimized pH. Generally, this study suggested that the ohmic heating can be used as a rapid and homogeneous cooking method for the preparation of sausages from greater lizardfish as a commercial low-valued fish.

Central Composite Optimization of Glycerosomes for the Enhanced Oral Bioavailability and Brain Delivery of Quetiapine Fumarate.

This study aimed to formulate and statistically optimize glycerosomal formulations of Quetiapine fumarate (QTF) to increase its oral bioavailability and enhance its brain delivery. The study was designed using a Central composite rotatable design using Design-Expert® software. The independent variables in the study were glycerol % w/v and cholesterol % w/v, while the dependent variables were vesicle size (VS), zeta potential (ZP), and entrapment efficiency percent (EE%). The numerical optimization process resulted in an optimum formula composed of 29.645 (w/v%) glycerol, 0.8 (w/v%) cholesterol, and 5 (w/v%) lecithin. It showed a vesicle size of 290.4 nm, zeta potential of -34.58, and entrapment efficiency of 80.85%. The optimum formula was further characterized for DSC, XRD, TEM, in-vitro release, the effect of aging, and pharmacokinetic study. DSC thermogram confirmed the compatibility of the drug with the ingredients. XRD revealed the encapsulation of the drug in the glycerosomal nanovesicles. TEM image revealed spherical vesicles with no aggregates. Additionally, it showed enhanced drug release when compared to a drug suspension and also exhibited good stability for one month. Moreover, it showed higher brain Cmax, AUC0-24, and AUC0-∞ and plasma AUC0-24 and AUC0-∞ in comparison to drug suspension. It showed brain and plasma bioavailability enhancement of 153.15 and 179.85%, respectively, compared to the drug suspension. So, the optimum glycerosomal formula may be regarded as a promising carrier to enhance the oral bioavailability and brain delivery of Quetiapine fumarate.

Thymoquinone-Enriched Naringenin-Loaded Nanostructured Lipid Carrier for Brain Delivery via Nasal Route: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Treatment of Depression.

In the current research, a thymoquinone-enriched naringenin (NGN)-loaded nanostructured lipid carrier (NLC) was developed and delivered via the nasal route for depression. Thymoquinone (TQ) oil was used as the liquid lipid and provided synergistic effects. A TQ- and NGN-enriched NLC was developed via the ultrasonication technique and optimized using a central composite rotatable design (CCRD). The optimized NLC exhibited the following properties: droplet size, 84.17 to 86.71 nm; PDI, 0.258 to 0.271; zeta potential, -8.15 to -8.21 mV; and % EE, 87.58 to 88.21%. The in vitro drug release profile showed the supremacy of the TQ-NGN-NLC in comparison to the NGN suspension, with a cumulative drug release of 82.42 ± 1.88% from the NLC and 38.20 ± 0.82% from the drug suspension. Ex vivo permeation study displayed a 2.21-fold increase in nasal permeation of NGN from the NLC compared to the NGN suspension. DPPH study showed the better antioxidant potential of the TQ-NGN-NLC in comparison to NGN alone due to the synergistic effect of NGN and TQ oil. CLSM images revealed deeper permeation of the NGN-NLC (39.9 µm) through the nasal mucosa in comparison to the NGN suspension (20 µm). Pharmacodynamic studies, such as the forced swim test and the locomotor activity test, were assessed in the depressed rat model, which revealed the remarkable antidepressant effect of the TQ-NGN-NLC in comparison to the NGN suspension and the marketed formulation. The results signify the potential of the TQ-enriched NGN-NLC in enhancing brain delivery and the therapeutic effect of NGN for depression treatment.

Optimization of Spray-Drying Process Parameters to Study Anti-Sticking Effect of Hydroxypropyl Methyl Cellulose-VLV on Corni fructus Extracts.

To prevent the sticking of Corni fructus extract (CFE) during spray drying, the anti-sticking effects of different excipients were compared. Hydroxypropyl methylcellulose (HPMC)-VLV showed a higher powder yield at a lower dosage (8% of total solids), and a lower solution viscosity, compared with HPMC-E5. Therefore, HPMC-VLV is a more effective excipient for reducing CFE sticking during spray drying. The spray-drying process parameters were optimized by central composite rotatable design/response surface methodology, and spray drying was conducted under the following conditions: Inlet air temperature, 126 °C; atomization pressure, 1.05 bar; pump speed, 7.7 mL/min. Scanning electron microscopy showed that the powder comprised shrunken spherical particles with particle sizes in the range of 2-30 µm. Analysis of dynamic surface tension and chemical elements on the powder surface showed that HPMC-VLV rapidly moved to the droplet surface owing to its surface activity. HPMC covered the droplet surface and reduced surface tension, achieving an anti-sticking effect. In conclusion, HPMC-VLV at a solid content of 8% significantly improved the spray drying and reduced sticking of CFE. The spray-drying process parameters were nonlinearly related to the dry product yield. Graphical Abstract.

Superporous acrylic acid and HPMC hydrogels of mefenamic acid: Formulation, characterization and optimization by central composite design.

The purpose of the study was to devise the superporous hydrogels (SPHs) of mefenamic acid (MA) to acquire the sustained action of the MA in the body. The superporous hydrogels of mefenamic acid were formulated by employing the gas blowing method. The central composite rotatable design (CCRD) was applied to optimize the effect of independent formulation factors like acrylic acid (AC), HPMC and glycerol (GLY) over dependent variables like porosity, viscosity, drug content and swelling ratio of superporous hydrogels in water, phosphate buffer (pH 6.8) and in 0.1N HCl (pH 1.2). A number of characteristics such as void fraction, surface morphology by Scanning electron microscopy (SEM) and in vitro drug release study were governed along with physico-chemical analysis by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and appraised statistically by employing the ANOVA. The comparative analgesic activity of optimized superporous hydrogel formulation SPH17 was also analyzed by using tail flick method. The Fourier transform infrared spectroscopy and Differential scanning calorimetry studies approved the physical compatibility between the polymers and the drug. The Scanning electron microscopy study specified micrographic insight about the structure of formed formulations comprising presence of pores, fibers and drug-hole aggregates. The superporous hydrogels were detected to be low dense as they expressed density lower than 0.75 g/cc. The decrease in concentration of the polymers and cross linker contributed towards the increase in the void fraction of the superporous hydrogel formulations. The optimized formulation SPH 17 exhibited a highly sustained release of MA for up to 10 h in the both 0.1 N HCl and phosphate buffer (66.6%) media. The non-fickian release of drug revealed the coupling of the diffusion and polymer relaxation mechanism of the drug release from the formulations. The obtained outcomes suggested that analgesic effect of SPH 17 was significantly (p < 0.05) higher than that of simple suspension of mefenamic acid and total analgesic effect duration for superporous hydrogel was also doubled as compared to the duration of analgesic effect produced by drug suspension. The successfully formulated SPH with HPMC K100M as a gelling agent had sustained the action of the mefenamic acid (MF) by improving its poor solubility and permeability. The introduction of inter-penetrating polymeric network (acrylic acid) using glycerol as a cross linker impart increased residence time to superporous hydrogels which ultimately enhanced the feasibility of using superporous hydrogel as oral sustained release devices particularly for gastric retention.

Development of ritonavir-loaded nanostructured lipid carriers employing quality by design (QbD) as a tool: characterizations, permeability, and bioavailability studies.

The objective of the present work was to optimize ritonavir (RTV)-loaded nanostructured lipid carriers (NLCs) to improve bioavailability using a quality by design (QbD)-based technique. Risk assessment was studied using "cause and effect" diagram followed by failure mode effect analysis (FMEA) to identify the effective high-risk variables for the formulation development. Quality target product profile (QTPP) and critical quality attributes (CQAs) were initially assigned for the proposed product. Central composite rotatable design (CCRD) was used to identify the individual and combined interactions of formulation variables. RTV-loaded NLC (RTV-NLC) was prepared using emulsification-ultrasonication method. The effect of formulation variables like ultrasound amplitude, lipid concentration, surfactant concentration on their responses like particle size, polydispersity index (PDI), and entrapment efficiency (EE) were studied by CCRD. The optimized formulation was subjected to lyophilization to obtain dry NLCs for solid-state analysis. DSC and PXRD investigations showed that RTV was molecularly dispersed in lipid matrix indicating amorphous form present in the formulation. FESEM and AFM depicted the spherical and uniform particles. The increase in solubility and dissolution rate is expected to be related to the molecular dispersion, amorphous state, of the drug in the nanoparticle. The optimized NLCs showed good physical stability during storage for 6 months. RTV-NLC was further subjected to in vitro studies and found a successful sustained release rate of 92.37 ± 1.03%. The parallel artificial membrane permeability assay (PAMPA) and everted gut sac model have demonstrated the permeation enhancement of RTV. In vivo study observed the enhanced bioavailability with 2.86-fold suggesting optimized NLC successfully overcome the issue of solubility.

Quality by design (QbD)-based fabrication of atazanavir-loaded nanostructured lipid carriers for lymph targeting: bioavailability enhancement using chylomicron flow block model and toxicity studies.

Atazanavir (ATV) is widely used as anti-HIV agent having poor aqueous solubility needs to modulate novel drug delivery system to enhance therapeutic efficiency and safety. The main objective of the present work was to fabricate ATV-loaded nanostructured lipid carriers (NLCs) employing quality by design (QbD) approach to address the challenges of bioavailability and their safety after oral administration. Herein, the main objective was to identify the influencing variables for the production of quality products. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (p < 0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, powder X-ray diffraction, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37 ± 1.03%) with a mechanism of Korsmeyer-Peppas model (r2 = 0.925, and n = 0.63). In vivo evaluation in Wistar rats showed significantly higher (p < 0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.

Investigation on mild extrusion cooking for development of snacks using rice and chickpea flour blends.

A study was conducted to optimize the mild extrusion cooking conditions for development of rice and chickpea based extrudates. The independent variables i.e. extrusion parameters (Screw speed, barrel temperature), feed moisture and proportions of rice flour and chickpea flour were varied using central composite rotatable design (CCRD), and their effects on system parameter- Specific mechanical energy (SME) and product characteristics i.e., water absorption index (WAI), water solubility index (WSI), bulk density (BD), expansion ratio (ER), breaking strength (BS), colour values (L*, a* and b*) and overall acceptability (OA) were studied. All the system and product responses were significantly affected by independent variables. Response surface and regression models were established to determine the responses as function of process variables. Models obtained were highly significant with high coefficient of determination (R2 ≥ 0.889). The optimum mild extrusion conditions obtained by numerical optimization for development of snacks were 102 °C barrel temperature, 281 rpm screw speed, 18.3% feed moisture and rice to chickpea flour ratio as 90:10. Storage studies confirmed that the developed snacks can be stored better in laminated pouches than in high density polyethylene (HDPE) bags for a period of 6 months under ambient conditions.