Subsequent Absorption Research Articles

Management of Ketamine Extravasation in a Pediatric Patient During Procedural Sedation.

Ketamine is a commonly used intravenous and intramuscular medication for procedural sedation within pediatric emergency medicine. There is limited availability of data on the rate of absorption and use of subcutaneous ketamine administration. We describe the case of a 12-year-old male who was sedated after extravasation and subsequent absorption of ketamine 1 mg/kg from a peripheral intravenous line (PIV). Despite being an unintended route, absorption of subcutaneous ketamine resulted in satisfactory procedural sedation with no complications. Given limited data on subcutaneous ketamine pharmacokinetics, the aim of this case report is to present the observed absorption of subcutaneous ketamine due to extravasation of PIV during a pediatric procedural sedation.

Drug Carriers

In recent years, there has been an exponential interest in the development of novel drug delivery systems using drug carriers. Drug carriers offer significant advantages over the conventional drug delivery systems in terms of high stability, high specificity, high drug loading capacity, controlled release of drug and ability to deliver both hydrophilic and hydrophobic drugs. As a result of their unique behaviors, drug carriers have a wide range of biomedical and industrial applications. Nanospheres are associated with a lot of benefits such as ease of administration to target sites, reduction in toxicity level and ease of passage via the capillary vessels. Hydrogel nanoparticles are useful in the treatment of inflammatory diseases, as bioresponsive hydrogels in drug delivery system and as a carrier in controlled drug delivery system. Carbon nanotubes have a large surface area which has the ability to adsorb or conjugate with a wide variety of therapeutic and diagnostic agents. They are useful in the areas of gene delivery, tissue regeneration and biosensor diagnosis. Liposomes are known to target a drug to a specific site. They entrap drugs which are released for subsequent absorption. They are used to achieve active targeting, increase efficacy and therapeutic index of drugs. Niosomes improve the solubility and oral bioavailability of poorly soluble drugs. They protect drugs from biological environment, increase the stability of entrapped drugs and they can easily reach the site of action. Aquasomes are nanoparticulate carriers that can be characterized for structural analysis. They preserve conformational integrity and biochemical stability of drugs. Ethosomes are noninvasive delivery carriers that enable drugs to reach the deep skin layers and the systemic circulation. They contain phospholipids which could be in form of phosphatidyl choline (PC), hydrogenated PC, phosphatidic acid (PA), Phosphatidyl serine (PS) and phosphatidyl inositol (PI). Ethosomes are known to increase skin permeation of drugs, improve biological activity and pharmacodynamics profile of drugs. This review aims to emphasize the importance of drug carriers in drug delivery system, and applications of drug carriers in various areas of research, technology and treatment.

Quadrupolar Ultrafast Charge Transfer in Diaminoazobenzene-Bridged Perylenediimide Triads.

Strong push-pull interactions between electron donor, diaminoazobenzene (azo), and an electron acceptor, perylenediimide (PDI), entities in the newly synthesized A-D-A type triads (A=electron acceptor and D=electron donor) and the corresponding A-D dyads are shown to reveal wide-band absorption covering the entire visible spectrum. Electrochemical studies revealed the facile reduction of PDI and relatively easier oxidation of diaminoazobenzene in the dyads and triads. Charge transfer reversal using fluorescence-spectroelectrochemistry wherein the PDI fluorescence recovery upon one-electron oxidation, deterring the charge-transfer interactions, was possible to accomplish. The charge transfer state density difference and the frontier orbitals from the DFT calculations established the electron-deficient PDI to be an electron acceptor and diaminoazobenzene to be an electron donor resulting in energetically closely positioned PDIδ- -Azoδ+ -PDIδ- quadrupolar charge-transfer states in the case of triads and Azoδ+ -PDIδ- dipolar charge-transfer states in the case of dyads. Subsequent femtosecond transient absorption spectral studies unequivocally proved the occurrence of excited-state charge transfer in these dyads and triads in benzonitrile wherein the calculated forward charge transfer rate constants, kf , were limited to instrument response factor, meaning >1012 s-1 revealing the occurrence of ultrafast photo-events. The charge recombination rate constant, kr , was found to depend on the type of donor-acceptor conjugates, that is, it was possible to establish faster kr in the case of triads (∼1011 s-1 ) compared to dyads (∼1010 s-1 ). Modulating both ground and excited-state properties of PDI with the help of strong quadrupolar and dipolar charge transfer and witnessing ultrafast charge transfer events in the studied triads and dyads is borne out from the present study.

The effects of different drying methods on the in vitro bioaccessibility of phenolics, antioxidant capacity, minerals and morphology of black ‘Isabel’ grape

The black Isabel grapes were dehydrated by hot-air drying (HAD), vacuum-drying (VD), ultrasound-assisted vacuum-drying (US-VD), freeze-drying (FD), and their physical properties, phenolic compounds, antioxidant capacities, and mineral content were determined before and after simulated in vitro digestion. Among drying methods, FD provided the highest retention of the phenolic compounds, whereas US-VD caused the highest loss. The changes of phenolics of grapes differed among the digestion phases depending on the state of grapes (fresh or dried) and the drying method. The chlorogenic acid was the major phenolic compound identified, followed by protocatechuic acid and catechin. The malvidin-3-O-glucoside was the major anthocyanin followed by 3-glucosides of petunidin, delphinidin, cyanidin, and peonidin in the fresh and FD samples. At the end of digestion, a significant decrease in the levels of phenolics, minerals and no presence of anthocyanins was observed. VD raisins exhibited a higher bioaccessibility index for most of the phenolic compounds. Potassium was the most bioaccessible mineral from grape samples. Our results together with the morphology of the grapes revealed that different microstructures created by drying and the disruption of the natural matrix would influence the release, transformation, and subsequent absorption of phenolics and minerals in the simulated digestion model.

Lactose intolerance: myths and facts. An update.

Lactose is the main carbohydrate present in human milk. It is a disaccharide made up of glucose and galactose. It is produced in the mammary glands, regardless of maternal diet. In addition to providing energy, it is the only source of dietary galactose, necessary for macromolecule synthesis, including oligosaccharides, glycoproteins, and glycolipids. It favors calcium, magnesium, and zinc absorption and retention. Its digestion by lactase and subsequent absorption occurs in the small intestine. Lactase deficiency may be classified into congenital primary (very rare), late-onset primary or secondary due to an injury of the intestine; it may cause intolerance with pain, abdominal distension, abdominal gas, and diarrhea. In the colon, it may be hydrolyzed by bifidobacteria and lactobacilli. The nutritional management of intolerance should always preserve breastfeeding. Lactose reduction or elimination should be transient, and eliminated food should be replaced with other similar in calorie, protein, mineral, and vitamin content.

In situ formed ultrafine metallic Ni from nickel (II) acetylacetonate precursor to realize an exceptional hydrogen storage performance of MgH2[sbnd]Ni-EG nanocomposite

It has been well known that doping nano-scale catalysts can significantly improve both the kinetics and reversible hydrogen storage capacity of MgH2. However, so far it is still a challenge to directly synthesize ultrafine catalysts (e.g., < 5 nm), mainly because of the complicated chemical reaction processes. Here, a facile one-step high-energy ball milling process is developed to in situ form ultrafine Ni nanoparticles from the nickel acetylacetonate precursor in the MgH2 matrix. With the combined action of ultrafine metallic Ni and expanded graphite (EG), the formed MgH2Ni-EG nanocomposite with the optimized doping amounts of Ni and EG can still release 7.03 wt.% H2 within 8.5 min at 300 °C after 10 cycles. At a temperature close to room temperature (50 °C), it can also absorb 2.42 wt.% H2 within 1 h. It can be confirmed from the microstructural characterization analysis that the in situ formed ultrafine metallic Ni is transformed into Mg2Ni/Mg2NiH4 in the subsequent hydrogen absorption and desorption cycles. It is calculated that the dehydrogenation activation energy of the MgH2Ni-EG nanocomposite is also reduced obviously in comparison with the pure MgH2. Our work provides a methodology to significantly improve the hydrogen storage performance of MgH2 by combining the in situ formed and uniformly dispersed ultrafine metallic catalyst from the precursor and EG.

Chewing the Fat with Microbes: Lipid Crosstalk in the Gut.

It is becoming increasingly important for any project aimed at understanding the effects of diet on human health, to also consider the combined effect of the trillions of microbes within the gut which modify and are modified by dietary nutrients. A healthy microbiome is diverse and contributes to host health, partly via the production and subsequent host absorption of secondary metabolites. Many of the beneficial bacteria in the gut rely on specific nutrients, such as dietary fiber, to survive and thrive. In the absence of those nutrients, the relative proportion of good commensal bacteria dwindles while communities of opportunistic, and potentially pathogenic, bacteria expand. Therefore, it is unsurprising that both diet and the gut microbiome have been associated with numerous human diseases. Inflammatory bowel diseases and colorectal cancer are associated with the presence of certain pathogenic bacteria and risk increases with consumption of a Western diet, which is typically high in fat, protein, and refined carbohydrates, but low in plant-based fibers. Indeed, despite increased screening and better care, colorectal cancer is still the 2nd leading cause of cancer death in the US and is the 3rd most diagnosed cancer among US men and women. Rates are rising worldwide as diets are becoming more westernized, alongside rising rates of metabolic diseases like obesity and diabetes. Understanding how a modern diet influences the microbiota and how subsequent microbial alterations effect human health will become essential in guiding personalized nutrition and healthcare in the future. Herein, we will summarize some of the latest advances in understanding of the three-way interaction between the human host, the gut microbiome, and the specific class of dietary nutrients, lipids.

Nitrogen-defect induced trap states steering electron-hole migration in graphite carbon nitride

Defect structures of semiconductors intrinsically regulate the trap states, excitons and active charge carriers for artificial photosynthesis systems. A g-C3N4 system with abundant nitrogen defects was prepared through a thermal polycondensation strategy to reveal the role of trap states and exhibited a 20-fold enhanced H2 evolution efficiency relative to bulk g-C3N4 under visible light irradiation. Subsequent femtosecond transient absorption spectroscopy study found that the N-defect induced shallow trap states can capture photogenerated electrons to inhibit deep trapping and direct recombination of photogenerated charges. The active electrons in shallow trap states can enhance the photocatalytic H2 evolution when compared with the inactive electrons in deep trap states. Mid-infrared transient absorption spectroscopy also confirmed the increased quantity of shallow-trapped electrons without interference of other signals. This work provides new insights for steering depth of trap states and photocatalytic processes through N defects to achieve high photocatalytic performance using femtosecond transient absorption spectroscopy.

Enhanced hydrogen desorption properties of MgH2 by highly dispersed Ni: The role of in-situ hydrogenolysis of nickelocene in ball milling process

Magnesium hydride is a promising hydrogen storage material and how to improve its sorption kinetics is one of challenges in practical applications. In this paper, a new approach is proposed to catalyze MgH2 with highly dispersed Ni nanoparticles by in-situ hydrogenolysis of nickelocene (NiCp2) in ball milling process. After ball milling under 4 MPa hydrogen atmosphere for 15 h, the MgH2–16.1 wt% NiCp2 sample exhibits a homogeneous morphology where the in-situ formed Ni nanoparticles with size of ~8 nm are highly dispersed in MgH2 matrix. During initial dehydrogenation, Ni would react with MgH2 to form Mg2Ni which inherits the configuration of its high dispersion. In the subsequent hydrogen absorption and desorption cycles, the much fine and highly dispersed Ni-based catalytic phase contributes to the superior hydrogen desorption kinetics of MgH2 with a high-capacity retention rate of ~96% after 50 cycles. This work demonstrates that the in-situ formation of highly dispersed catalytic species is beneficial for improving hydrogen storage properties of MgH2.

In vitro evidence of the influence of complexation of Pu and Am on uptake by human lung epithelial cells Calu-3

Understanding the mechanisms involved in retention and clearance of actinides from the lungs after accidental intake is essential for the evaluation of the associated radiological risks. Although the absorption of radioelements has been shown in vivo to depend on their nature and physico-chemical properties, their mechanisms of translocation remain unknown. In this study, we have evaluated in vitro the binding and uptake by bronchial epithelial cells Calu-3 of 2 transuranic actinides, plutonium (Pu) and americium (Am), as the first steps of translocation across the pulmonary barrier. For this purpose, Calu-3 cells grown to confluence in 24-well plates were exposed to the radioelements for 24 h under various culture conditions. Two compartments were identified for the association of actinides to cells, corresponding to the membrane bound and internalized fractions. Binding of Pu was slightly higher than of Am, and depended on its initial chemical form (nitrate, citrate, colloids). Uptake of Pu and Am nitrate was higher in serum-free conditions than in supplemented medium, with an active mechanism involved in Pu internalization. Overall, our results suggest that complexation of actinides to bioligands may have an influence on their uptake by pulmonary epithelial cells, and therefore possibly on their subsequent absorption into blood.

Octaphyrin(1.0.1.0.1.0.1.0) as an Organic Electrode for Li and Na Rechargeable Batteries.

Organic electrode materials for rechargeable batteries have come into the spotlight due to their structural tunability and diversity. In this study, it is found that bisnickel(II) meso-mesityloctaphyrin(1.0.1.0.1.0.1.0) (Oct) is exhibiting multiple oxidation states with extended π-conjugation pathways to afford an active electrode material in Li and Na-organic batteries and secure interactions with Li+ (or Na+ ) and anions enabling efficient dual ionic charge/discharge behaviors. Cyclic voltammograms of the Oct electrode elucidate constantly reversible redox processes in both Li and Na organic batteries and pseudocapacitive behaviors at high currents. Subsequent absorption transformations in CV-UV/VIS/NIR spectroscopic analysis and TD-DFT calculations upon the different redox states of Oct conclusively indicate that six electrons are involved in redox-interconversions per unit cycle with corresponding absorption transformations, which also assessed with charge-and-discharge cell capacities. Significant contributions of the pseudocapacitive processes over the diffusion-controlled processes proceeding in Li- and Na-Oct cells induced fast charge/discharge performance and long-term cyclability.

Lamotrigine therapy in patients after bariatric surgery: Potentially hampered solubility and dissolution

Bariatric surgery is an effective treatment of obesity and related comorbidities. With surgery, the stomach undergoes major anatomical/physiological changes that may affect the oral exposure of drugs, especially marginally soluble weak bases, such as lamotrigine. The aim of this work was to study the solubility/dissolution of lamotrigine in conditions simulating the stomach before vs. after bariatric surgery. Lamotrigine solubility was studied in-vitro, as well as ex-vivo in gastric content aspirated from patients before vs. after bariatric surgery. We then compared the dissolution kinetics of various marketed lamotrigine products in pre- vs. post-operative stomach conditions, different in volume, pH, agitation strength and speed. Decreased lamotrigine solubility with increasing pH (from 1.37 ± 0.09 (pH = 1) to 0.22 ± 0.03 mg/mL (pH = 7)) was obtained. Twelve-fold higher lamotrigine solubility was revealed in gastric content aspirated before vs. after surgery (8.5 ± 0.7 and 0.7 ± 0.01 mg/mL, respectively). Dissolution studies showed that only the lowest dose (25 mg) fully dissolved in the post-surgery stomach conditions, while at higher doses, lamotrigine tablet dissolution was impaired. Neither fast-dissolving tablet, nor tablet crushing, helped resolving this problem. Based on these results, and given that dissolution of the drug dose governs the subsequent absorption, close monitoring of this essential drug is advised after bariatric surgery.

In vitro digestion, absorption and biological activities of acylated anthocyanins from purple sweet potatoes (Ipomoea batatas)

Purple sweet potatoes (PSP) are widely used as color enhancers in food formulations. Investigations on the stability of PSP polyphenolics during simulated digestion and subsequent absorption in a Caco-2 cell monolayer model were accomplished. Measures of bioactive activities were also assessed in vitro. PSP whole polyphenolic extracts as a control (WC) were compared to isolates enriched in anthocyanins (AC) or non-anthocyanin phenolics (NAP). Anthocyanins were also alkali-hydrolyzed to remove acylated moieties. Compounds were subjected to simulated gastro-intestinal digestions where non-hydrolyzed anthocyanins showed higher stability compared to alkali-hydrolyzed. For many alkali-hydrolyzed anthocyanins, the transport through a Caco-2 cell monolayer was reduced. PSP fractions significantly increased the generation of reactive oxygen species in HT-29 cells and was suppressive in the CCD-18Co cells while down-regulated mRNA expression of inflammatory markers. Results indicate the importance of PSP composition and the effects of acyl moieties on anthocyanin stability and functional properties for food colors.

A Physiological-Based Model for Simulating the Bioavailability and Kinetics of Sulforaphane from Broccoli Products.

There are no known physiological-based digestion models that depict glucoraphanin (GR) to sulforaphane (SR) conversion and subsequent absorption. The aim of this research was to make a physiological-based digestion model that includes SR formation, both by endogenous myrosinase and gut bacterial enzymes, and to simulate the SR bioavailability. An 18-compartment model (mouth, two stomach, seven small intestine, seven large intestine, and blood compartments) describing transit, reactions and absorption was made. The model, consisting of differential equations, was fit to data from a human intervention study using Mathwork’s Simulink and Matlab software. SR urine metabolite data from participants who consumed different broccoli products were used to estimate several model parameters and validate the model. The products had high, medium, low, and zero myrosinase content. The model’s predicted values fit the experimental values very well. Parity plots showed that the predicted values closely matched experimental values for the high (r2 = 0.95), and low (r2 = 0.93) products, but less so for the medium (r2 = 0.85) and zero (r2 = 0.78) myrosinase products. This is the first physiological-based model to depict the unique bioconversion processes of bioactive SR from broccoli. This model represents a preliminary step in creating a predictive model for the biological effect of SR, which can be used in the growing field of personalized nutrition.

Pharmacokinetic profile of a novel sustained-release caffeine with extended benefits on alertness and mood: A randomized, double-blind, single-dose, active-controlled, crossover study

• Xtenergy™ demonstrated a slow absorption and sustained plasma caffeine levels based on T max , t 1/2 and AUC data. • T max was 325.53% higher ( p < 0.05) and t 1/2 was 21.34% higher ( p < 0.05) for Xtenergy™ as compared to immediate release caffeine. • Xtenergy™ demonstrated similar total exposure as IRC based on the 90% CI of 84.63% - 114.45% for AUC 0–24. • Slow-Release caffeine showed significant beneficial effects ( p < 0.05) at several of the time points on alertness, tiredness, overall mood, jitteriness and less tenseness without any safety issues. Oral consumption of caffeine typically leads to its instant release and subsequent rapid absorption, high plasma caffeine levels followed by a quick steep decline reducing its beneficial effects which is frequently referred to as “caffeine crash”. To overcome this limitation, we developed a new slow and sustained-release caffeine (SRC) formulation, Xtenergy™. The primary objective was to compare the plasma pharmacokinetic profile of SRC with immediate-release caffeine (IRC). Secondary objectives included the use of caffeine research visual analogue scales (Caff - VAS) to evaluate some of the nootropic benefits of SRC and safety assessments. This was a randomized, double-blind, single-dose, active-controlled, crossover study. Twenty-six subjects were randomized to receive 200 mg caffeine from SRC and IRC in a crossover fashion as per the randomization schedule. Blood samples were collected at -4, 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 h in each period. Plasma caffeine levels were analyzed by a validated LC-MS/MS method. The changes in Caff-VAS relaxed, alert, jittery, tired, tense, headache, overall mood from baseline i.e., 0 to 1, 2, 4, 6, 8, 10, and 12 h were evaluated. Twenty-four male subjects with mean age 32.71±6.18 years completed the study. The median T max was 325.53% higher ( p < 0.05) for SRC as compared to IRC (4.00 vs. 0.94 h) and mean t 1/2 was 21.34% higher ( p < 0.05) for SRC as compared to IRC (9.± 4.56 vs. 7.61± 3.98 h). SRC demonstrated similar total exposure as IRC based on the 90% CI of 84.63% - 114.45% for ln-transformed AUC 0–24 . AUC 4–8 and AUC 6–12 were 6.80% and 22.84% higher for SRC as compared to IRC, respectively. Compared to IRC, SRC showed significant beneficial effects ( p < 0.05) on feelings of being more alert, less tired, better overall mood, less jittery and less tense at several of the study time points. No safety concerns were observed. SRC showed a slow absorption and sustained plasma caffeine levels. Compared to IRC, we saw significant benefits of SRC at several of the time points on alertness, tiredness, overall mood, jitteriness and tenseness without any safety concerns.

Thyroid Disorders.

Thyroid Disorders.

Effect of the Proton Pump Inhibitor Esomeprazole on the Systemic Exposure of Capecitabine: Results of A Randomized Crossover Trial.

Retrospective data suggest that gastric acid reduction by proton pump inhibitors (PPIs) impairs the dissolution and subsequent absorption of capecitabine, and thus potentially reduces the capecitabine exposure. Therefore, we examined prospectively the effect of esomeprazole on the pharmacokinetics of capecitabine. In this randomized crossover study, patients with cancer were assigned to 2 sequence groups, each consisting of 3 phases: capecitabine with esomeprazole administration 3hours before (phase A), capecitabine alone (phase B), and capecitabine concomitant with cola and esomeprazole co-administration 3hours before (phase C). The primary end point was the relative difference (RD) in exposure to capecitabine assessed by the area under the plasma concentration-time curve from zero to infinity (AUC0-inf ) and analyzed by a linear mixed effect model. Twenty-two evaluable patients were included in the analysis. After esomeprazole, there was a 18.9% increase in AUC0-inf of capecitabine (95% confidence interval (CI) -10.0% to 57.0%, P=0.36). In addition, capecitabine half-life was significantly longer after esomeprazole (median 0.63hours vs. 0.46hours, P=0.005). Concomitant cola did not completely reverse the effects observed after esomeprazole (RD 3.3% (95% CI -16.3 to 27.4%, P=1.00). Capecitabine exposure is not negatively influenced by esomeprazole cotreatment. Therefore, altered capecitabine pharmacokinetics do not explain the assumed worse clinical outcome of PPI-cotreated patients with cancer.

Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications.

There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an “absorption window” or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.

Evaluation and GWAS of radicle gravitropic response in a core rice germplasm population

AimsSince gravitropism is one of the primary determinants of root development, facilitating root penetration into soil and subsequent absorption of water and nutrients, we studied this response in rice.MethodsThe gravitropism of 226 Chinese rice micro-core accessions and drought-resistant core accessions were assessed through the modified gravity-bending experiment and genome-wide association analysis (GWAS) was used to map the associated QTLs.ResultsThe average value of gravitropic response speed of seminal roots was 41.05°/h, ranging from 16.77°/h to 62.83°/h. The gravity response speed of Indica (42.49°/h) was significantly (P < 0.002) higher than Japonica (39.71°/h) subspecies. The gravitational response speed of seminal roots was significantly positively correlated with the number of deep roots (r = 0.16), the growth speed of seminal roots (r = 0.21) and the drought resistance coefficient (r = 0.14).ConclusionsIn total, 3 QTLs (quantitative traits) associated with gravitropic response speed were identified on chromosome 4, 11 and 12. There are some known QTLs relating to roots traits and drought resistance located nearby the QTLs identified here, which confirms the close relationship between radicle gravitropism and the drought resistance. From within these intervals, 5 candidate genes were screened and verified by qPCR in a few rice varieties with extreme phenotypic values, demonstrating that gene LOC_Os12g29350 may regulate gravitropism negatively. This may be a promising candidate to be confirmed in further studies.

Photoinduced Charge Separation Prompted Intervalence Charge Transfer in a Bis(thienyl)diketopyrrolopyrrole Bridged Donor-TCBD Push-Pull System.

Intervalence charge transfer (IVCT), a phenomenon observed in molecular systems comprised of two redox centers differing in oxidation states by one unit, is reported in a novel, newly synthesized, multi-modular donor-acceptor system comprised of central bis(thienyl)diketopyrrolopyrrole (TDPP) hosting two phenothiazine-tetracyanobutadiene (PTZ-TCBD) entities on the opposite sides. One-electron reduction of TCBD promoted electron exchange between the two TCBD resulting in IVCT transition in the near-infrared region. The stabilization energy, -ΔGcom and comproportionation equilibrium constant, Kcom calculated from peak potentials of the split reduction waves were found to be 1.06×104 J mol-1 , and 72.3 M-1 , respectively. Further, the IVCT transition was also witnessed during the process of thermodynamically feasible electron transfer upon excitation of the TDPP entity in the system, and served as a diagnostic marker to characterize the electron transfer product. Subsequent transient absorption spectral studies and data analysis by Global and Target analyses revealed occurrence of ultrafast charge separation (kcs ≈1010 s-1 ) owing to the close proximity and good communication between the entities of the multi-modular donor-acceptor system. The role of central TDPP in promoting IVCT is borne out from the present investigation.