Sweet pepper and its principle constituent capsiate: functional properties and health benefits.

Capsiate is a non-pungent analogue of capsaicin. It belongs to the family of capsinoids which are esters of vanillyl alcohol with fatty acids while capsaicin belongs to the family of capsaicinoids that are amides of vanillylamine with a variety of branched-chain fatty acids. While capsaicin is extensively reported for plethora of pharmacological actions, capsiate remains much less explored. Extracted from various species of Capsicum plant, the molecule has also been chemically synthesized via a number of synthetic and enzymatic routes. Based on its action on transient receptor potential vanilloid subfamily member 1 receptors, recent research has focused on its potential roles in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. Its toxicity profile has been reported to be much safe. The molecule, however, faces the challenge of low aqueous solubility and stability. It has been commercialized for its use as a weight loss supplement. However, the therapeutic potential of the compound which is much beyond boosting metabolism remains unexplored hitherto. This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. Discussed also are potential future directions for formulation strategies to develop efficient, safe and cost-effective dosage forms of capsiate to explore its role in various disease conditions. The databases investigated include Cochrane library, Medline, Embase, Pubmed and in-house databases. The search terms were "capsiate," "capsinoids," "thermogenesis," and their combinations. The articles were screened for relevance by going through their abstract. All the articles pertaining to physicochemical, physiological, pharmacological and therapeutic effects of capsiate have been included in the manuscript.

Novel Nanostructured Lipid Carriers Co-Loaded with Mesalamine and Curcumin: Formulation, Optimization and In Vitro Evaluation.

PURPOSE: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs). METHODS: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined. RESULTS: The PS, ZP and EE were found to be 85.26 nm, -23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed. CONCLUSION: The outcomes of study deciphered successful formulation of Mes-Cur NLCs.

Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats.

The present investigation is focused on improving oral bioavailability of poorly soluble and lipophilic drugs, curcumin (CRM) and duloxetine (DXH), through the solid self-nanoemulsifying drug delivery system (S-SNEDDS) and identifying their potential against attenuation of NP in chronic constriction injury (CCI)-induced rats through the solid self-nanoemulsifying drug delivery system (S-SNEDDS). The optimized batch of S-SNEDDS reported was containing CRM and DXH (30 mg each), castor oil (20% w/w), tween-80 (40% w/w), transcutol-P (40% w/w), and syloid 244 FP (1 g). The high dose of each of naïve CRM (NCH), naïve DXH (NDH), physical mixture of DXH and CRM (C-NCM-DXH), S-SNEDDS-CRM (SCH), S-SNEDDS-DXH (SDH), and S-SNEDDS-CRM-DXH (C-SCH-SDH) was subjected for MTT assay. The developed formulations were subjected to pharmacokinetic studies and results showed about 8 to 11.06 and 2-fold improvement in oral bioavailability of CRM and DXH through S-SNEDDS. Furthermore, CCI-induced male Wistar rats were treated with SSNEDDS containing CRM and DXH, S-SNEDDS containing individual drug, individual naïve forms, and their combination from the day of surgery for 14 days and evaluated for behavioral at pre-determined time intervals. On the terminal day, animals were sacrificed to assess tissue myeloperoxidase, superoxide anion, protein, tumor necrosis factor-α, total calcium levels, and histopathological changes. Pronounced effect was observed in rats treated with S-SNEDDS containing both drugs with respect to rats receiving any of other treatments owing to enhanced oral bioavailability through S-SNEDDS. Therefore, it can be concluded that S-SNEDDS of both drugs and their coadministration can accelerate the prevention of NP.

Impact of solidification on micromeritic properties and dissolution rate of self-nanoemulsifying delivery system loaded with docosahexaenoic acid.

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of docosahexaenoic acid (DHA) is reported with the aim to achieve enhanced dissolution rate. The optimized composition of liquid SNEDDS (L-SNEDDS) formulation was Labrafil M1944 CS, 47% v/v Tween 80, 27% v/v Transcutol P, and 0.1% v/v DHA. L-SNEDDS were solidified using Syloid XDP 3150 as solid porous carrier. The droplet size, polydispersity index, zeta potential, percentage drug loading, and cloud point for L-SNEDDS were found to be 43.51 ± 1.36 nm, 0.186 ± 0.053, -19.20 ± 1.21 mV, 93.23 ± 1.71, and 88.60 ± 2.54 °C, respectively. Similarly, for solid SNEDDS (S-SNEDDS) the above parameters were found to be 57.32 ± 1.87 nm, 0.261 ± 0.043, -16.60 ± 2.18 mV, 91.23 ± 1.88, and 89.50 ± 1.18 °C, respectively. The formulations (L-SNEDDS, S-SNEDDS powder, and S-SNEDDS tablet) showed significant (p<.05) improvement in dissolution rate of drug in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) as compared to unprocessed DHA. In both the dissolution media, the dissolution rate was found more that 85% in 90 min. Absence of drug precipitation, phase separation, and turbidity during thermodynamic stability studies indicated that the developed SNEDDS were stable. Hence, it was concluded that SNEDDS have offered sufficient stability as well as dissolution rate of DHA.

Impact of various solid carriers and spray drying on pre/post compression properties of solid SNEDDS loaded with glimepiride: in vitro-ex vivo evaluation and cytotoxicity assessment.

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80, and ethanol were used as oil, surfactant, and co-surfactant, respectively as independent variables. The optimized composition of SNEDDS formulation (F1) was 10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.005% w/v glimepiride. Further, the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, dissolution, and diffusion. Both, liquid and solid-SNEDDS have shown release of more than 90% within 10 min. Results of permeation studies performed on Caco-2 cell showed that optimized SNEDDS exhibited 1.54 times higher drug permeation amount and 0.57 times lower drug excretion amount than that of market tablets at 4 hours (p < .01). Further, the cytotoxicity study performed on Caco-2 cell revealed that the cell viability was lower in SNEDDS (92.22% ± 4.18%) compared with the market tablets (95.54% ± 3.22%; p > .05, i.e. 0.74). The formulation was found stable with temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline glimepiride was observed in amorphous state in solid SNEDDS when characterized through DSC, PXRD, and FT-IR studies. The study revealed successful formulation of SNEDDS for glimepiride.

Turbulence in continuous flow surface aeration systems.

Turbulence characteristics in an optimal continuous surface aeration system were investigated in this study. The experimental system consists of a rectangular tank, where flow is driven by equally spaced aerators placed on the liquid surface. The mass-transfer coefficient and turbulent parameters at the tank's inlet and outlet were measured to enable analysis of their interdependent relationships. The turbulence parameters are linked closely to the system's mass-transfer process. Turbulent bursting analysis has shown that ejection and sweep events govern the hydrodynamics of the systems. Turbulent intensity increases with increasing speed of rotation, and consequently the mass-transfer coefficient also increases. The universal probability distribution functions of the velocity fluctuations in continuous flow surface aeration systems follow the Gram-Charlier series, based on exponential distribution, and the theoretical and experimental curves match.

Stable Co-crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization.

Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60-70°C for 15 min, followed by cooling at room temperature for 24 h. FT-IR spectroscopy revealed no molecular interaction between acids and drug as the internal structure and their geometric configurations remain unchanged. Differential scanning calorimetry revealed closer melting points of raw glipizide and its co-crystals, which speculates absence of difference in crystallinity as well as intermolecular bonding of the co-crystals and drug. PXRD further revealed that all the co-crystals were having similar crystallinity as that of raw glipizide except glipizide-malonic acid co-crystals. This minor difference in the relative intensities of some of the diffraction peaks could be attributed to the crystal habit or crystal size modification. SEM revealed difference in the crystal morphology for all the co-crystals. Micromeritic, solubility, dissolution, and stability data revealed that among all the prepared co-crystals, glipizide-stearic acid co-crystals were found superior. Hence, it was concluded that glipizide-stearic acid co-crystals could offer an improved drug design strategy to overcome dissolution and bioavailability related challenges associated with lipophilic glipizide.

Optimization of waste combinations during in-vessel composting of agricultural waste.

In-vessel composting of agricultural waste is a well-described approach for stabilization of compost within a short time period. Although composting studies have shown the different combinations of waste materials for producing good quality compost, studies of the particular ratio of the waste materials in the mix are still limited. In the present study, composting was conducted with a combination of vegetable waste, cow dung, sawdust and dry leaves using a 550 L rotary drum composter. Application of a radial basis functional neural network was used to simulate the composting process. The model utilizes physico-chemical parameters with different waste materials as input variables and three output variables: volatile solids, soluble biochemical oxygen demand and carbon dioxide evolution. For the selected model, the coefficient of determination reached the high value of 0.997. The complicated interaction of agricultural waste components during composting makes it a nonlinear problem so it is difficult to find the optimal waste combinations for producing quality compost. Optimization of a trained radial basis functional model has yielded the optimal proportion as 62 kg, 17 kg and 9 kg for vegetable waste, cow dung and sawdust, respectively. The results showed that the predictive radial basis functional model described for drum composting of agricultural waste was well suited for organic matter degradation and can be successfully applied.

Probability distribution of turbulence in curvilinear cross section mobile bed channel.

The present study investigates the probability density functions (PDFs) of two-dimensional turbulent velocity fluctuations, Reynolds shear stress (RSS) and conditional RSSs in threshold channel obtained by using Gram-Charlier (GC) series. The GC series expansion has been used up to the moments of order four to include the skewness and kurtosis. Experiments were carried out in the curvilinear cross section sand bed channel at threshold condition with uniform sand size of d50 = 0.418 mm. The result concludes that the PDF distributions of turbulent velocity fluctuations and RSS calculated theoretically based on GC series expansion satisfied the PDFs obtained from the experimental data. The PDF distribution of conditional RSSs related to the ejections and sweeps are well represented by the GC series exponential distribution, except that a slight departure of inward and outward interactions is observed, which may be due to weaker events. This paper offers some new insights into the probabilistic mechanism of sediment transport, which can be helpful in sediment management and design of curvilinear cross section mobile bed channel.

Effect of emergent vegetation on riverbank erosion with sediment mining.

The present work investigates the combined effects of the upstream sediment mining pit and vegetation on the riverbank using emergent rigid vegetation beyond the toe on the flow structure and morphological changes due to fluvial erosion. A steep gradient of streamwise velocity and other turbulence parameters such as Reynolds shear stress (RSS), transverse RSS, and turbulent kinetic energy (TKE) at the interface of the vegetated and unvegetated part of the test segment was observed. The cross-sectional analysis showed that vegetation increased the velocity of the unvegetated main channel, and the sandpit increased even the near-bed velocity with a similar trend in its longitudinal variation at the center line of the main channel. The abrupt variation in RSS and transverse RSS at the location of the berm induces instability and erodes the berm present at the toe of the riverbank. The combination of the vegetation and sandpit led to increased TKE of the flow at the near-bed and berm locations. The morphological analysis showed complete riverbank erosion in both cases of the unvegetated riverbank, i.e., without or with an upstream pit. The installed stems of rigid vegetation on the riverbank helped decrease the fluvial erosion of the riverbank, and its profile observed minimal changes over the length of the test segment. However, the main channel erosion was amplified due to the vegetation (in no-pit case) at the beginning of the test segment, which eroded the bed of the main channel by about 67% of the bed thickness. Also, in the vegetated riverbank cases, the upstream pit caused an increase in erosion by 7.66% at the center of the main channel. The study helps establish the hypothesis of negating the effects of sediment mining on bank erosion by using the rigid vegetation on the riverbank beyond its toe location, which performed well by maintaining the riverbank profile.