Advances in Nanocarrier Systems for Overcoming Formulation Challenges of Curcumin: Current Insights.

Curcumin, an organic phenolic molecule that is extracted from the rhizomes of Curcuma longa Linn, has undergone extensive evaluation for its diverse biological activities in both animals and humans. Despite its favorable characteristics, curcumin encounters various formulation challenges and stability issues that can be effectively addressed through the application of nanotechnology. Nano-based techniques specifically focused on enhancing solubility, bioavailability, and therapeutic efficacy while mitigating toxicity, have been explored for curcumin. This review systematically presents information on the improvement of curcumin's beneficial properties when incorporated, either individually or in conjunction with other drugs, into diverse nanosystems such as liposomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, solid-lipid nanoparticles, and nanostructured lipid carriers. Additionally, the review examines ongoing clinical trials and recently granted patents, offering a thorough overview of the dynamic landscape in curcumin delivery. Researchers are currently exploring nanocarriers with crucial features such as surface modification, substantial loading capacity, biodegradability, compatibility, and autonomous targeting specificity and selectivity. Nevertheless, the utilization of nanocarriers for curcumin delivery is still in its initial phases, with regulatory approval pending and persistent safety concerns surrounding their use.

Design of Experimental Approach for Development of Rapid High Performance Liquid Chromatographic Process for Simultaneous Estimation of Metoprolol, Telmisartan, and Amlodipine from Formulation: Greenness and Whiteness Evaluation.

The design of an experimental approach, the Box-Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for quantification of a ternary mixture of metoprolol (MET), telmisartan (TEL), and amlodipine (AML) from the formulation. The perturbation plots, contour, and 3D response surface pictures were developed to study the impact of each variable on the analytes' retention time and the probable interaction between the parameters with fewer chromatographic runs. The optimized HPLC method separated the three analytes within 5 min with excellent selectivity and peak shape on a Zorbax C18 HPLC column using acetonitrile and phosphate buffer (20 mM, pH 5.8) with isocratic elution at a 1.1 mL/min flowrate. A wavelength 230 nm was utilized to monitor the elute. The validation of proposed method demonstrated a wide linearity range of 10-200 µg/mL for MET and TEL and 5-50 µg/mL for AML along with an excellent correlation coefficient. The correctness of the HPLC approach was further confirmed by excellent recovery of the added amount of analytes utilizing the standard addition technique. The recommended HPLC approach was employed safely for quality assurance of the formulation, because the evaluation of the method's greenness and whiteness confirmed the environmentally friendly nature of the approach.

Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole.

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1-E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm2) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.

Pharmacological Features of 18ß-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18ß-glycyrrhetinic acid (18ßGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18ßGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18ßGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18ßGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18ßGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18ßGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges.

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into ß-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (-17 to -26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (ß-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 µg/mL) in comparison to SES (106 µg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.

Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway.

Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we tried to explore the chemical composition and the hepato-protective effect of ethanolic aqueous extract of CARD to mitigate APAP-induced hepatic toxicity and elucidate its underlying mechanism of action. MATERIAL AND METHODS: Aqueous CARD extract was subjected to LC-TOF-MS analysis to separate and elucidate some of its components. In vivo animal experiments involved five groups of animals. In the normal and cardamom groups, mice were administered either saline or CARD (200 mg/kg), respectively, orally daily for 16 days. In the APAP group, the animals were administered saline orally daily for 15 days, and on the 16th day, animals were administered APAP (300 mg/kg) IP for the induction of acute hepatic failure. In the CARD 200 + APAP group, mice were administered CARD (200 mg/kg) for 15 days, followed by APAP on the 16th day. RESULTS: The aqueous extract of CARD showed several compounds, belonging to polyphenol, flavonoids, cinnamic acid derivatives and essential oil components. In the in vivo investigations, APAP-induced impaired liver function, several histopathological alterations, oxidative stress and inflammatory and apoptotic status signified severe hepatic failure. Whereas, pretreatment with the CARD extract prior to APAP administration diminished serum levels of the hepatic function test and augmented Nrf2 nucleoprotein and HO-1 and NQO-1. CARD down-regulated MDA, inflammatory mediators (IL-1ß, IL-6, TNF-α and NF-κB) and apoptotic markers (caspase 3 and 9 and Bax) and amplified the activities of SOD, catalase, GSH-Px and GSH-R in hepatic tissue samples. CONCLUSION: CARD extract mitigated the hepatic toxicity induced by APAP. The underlying mechanism of action of such hepato-protective action may be through upregulation of the Nrf2/HO-1/NQO-1 pathway with subsequent alleviation of the oxidative stress, inflammation and apoptosis induced by APAP. Many of the compounds identified in the CARD extract could be attributed to this pharmacological action of the extract.

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels.

Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.

Computational Design, Synthesis, and Pharmacological Evaluation of Naproxen-Guaiacol Chimera for Gastro-Sparing Anti-Inflammatory Response by Selective COX2 Inhibition.

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.

Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.

A series of 2,3-dihydroquinazolin-4(1H)-one derivatives (3a-3m) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 3l and 3m with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound 3k with an imidazole ring at the 2-position of the dihydroquinazolin-4(1H)-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively. The computational results revealed the mycobacterial pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (BioA) enzyme as the potential target for the tested compounds. In vitro, ADMET calculations and cytotoxicity studies against the normal human dermal fibroblast cells indicated the safety and tolerability of the test compounds 3k-3m. Thus, compounds 3k-3m warrant further optimization to develop novel BioA inhibitors for the treatment of drug-sensitive H37Rv and drug-resistant MTB.

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies.

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1−F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1) and Poloxamer 407 (X2)) on the response effects (gelation temperature (Y1) and % drug release (Y2) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) Cmax (~4-fold) and AUC0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS.

Sensitivity Enhanced Ecofriendly UV Spectrophotometric Methods for Quality Control of Telmisartan and Benidipine Formulations: Comparison of Whiteness and Greenness with HPLC Methods.

The development of an environmentally friendly analytical technique for simultaneous measurement of medicines with large concentration differences is difficult yet critical for environmental protection. Hence, in this work, new manipulated UV-spectroscopic methods with high scaling factors were established for concurrent quantification of telmisartan (TEL) and benidipine (BEN) in fixed-dose combinations. Two different methods were developed and established by calculation of peak height at zero crossing point of second derivative and the ratio of first derivative spectra with a scaling factor of 200 and 100, respectively. The absorption difference between the peaks and troughs of the ratio spectra, as well as continuous subtraction from ratio spectra, were established as additional methods. In addition, new procedures were validated using ICH recommendations. The proposed methods' linearity curves were constructed in the range of 0.5-10 µg mL-1 and 1-30 µg mL-1 for BEN and TEL, respectively, under optimized conditions. Furthermore, both the detection (0.088-0.139 µg mL-1 for BEN and 0.256-0.288 µg mL-1 for TEL) and quantification limits (0.293-0.465 µg mL-1 for BEN and 0.801-0.962 µg mL-1 for TEL) were adequate for quantifying both analytes in the formulation ratios. The accuracy and precision were confirmed by the good recovery percent (98.37%-100.6%), with low percent relative error (0.67%-1.70%) and less than 2 percent relative standard deviation, respectively. The specificity of the methods was proven by accurate and precise outcomes from the standard addition method and analysis of laboratory mixed solutions with large differences in concentrations of both analytes. Finally, the BEN and TEL content of the formulations was determined simultaneously without prior separation using these first ever reported spectroscopic methods. Furthermore, developed UV derivative spectroscopic methods demonstrated high greenness and whiteness when compared to the reported HPLC methods. These findings show that the projected methods were effective, practical, and environmentally acceptable for quality control of BEN and TEL in multicomponent formulations.

An Experimental Design Approach to Quantitative Expression for Quality Control of a Multicomponent Antidiabetic Formulation by the HILIC Method.

A rapid and reproducible hydrophilic liquid chromatography (HILIC) process was established for concomitant determination of remogliflozin etabonate (RE), vildagliptin (VD), and metformin (MF) in a formulation. A face-centered central composite experimental design was employed to optimize and predict the chromatographic condition by statistically studying the surface response model and design space with desirability close to one. A HILIC column with a simple mobile phase of acetonitrile (65% v/v) and 20 mM phosphate buffer (35% v/v, pH 6, controlled with orthophosphoric acid) was used to separate RE, VD, and MF. RE, VD, and MF were separated in 3.6 min using an isocratic mode mobile phase flow at a flow rate of 1.4 mL at room temperature, and the analytes were examined by recording the absorption at 210 nm. The developed HILIC method was thoroughly validated for all parameters recommended by ICH, and linearity was observed in the ranges 20−150 µg/mL, 10−75 µg/mL, and 50−750 µg/mL for RE, VD, and MF, respectively, along with excellent regression coefficients (r2 > 0.999). The calculated percentage relative deviation and relative error ascertained the precision and accuracy of the method. The selectivity and accuracy were further confirmed by the high percentage recovery of added standard drugs to the formulation using the standard addition technique. The robustness of the HILIC processes was confirmed by developing a half-normal probability plot and Pareto chart, as the slight variation of a single factor had no significant influence on the assay outcomes. Utilization of the optimized HILIC procedure for concurrent quantification of RE, VD, and MF in solid dosage forms showed accurate and reproducible results. Hence, the fast HILIC method can be regularly employed for the quality assurance of pharmaceutical preparations comprising RE, VD, and MF.

1,2,3-Triazolyl-tetrahydropyrimidine Conjugates as Potential Sterol Carrier Protein-2 Inhibitors: Larvicidal Activity against the Malaria Vector Anopheles arabiensis and In Silico Molecular Docking Study.

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure-activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules' potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.

Biotechnological Approaches for Production of Artemisinin, an Anti-Malarial Drug from Artemisia annua L.

Artemisinin is an anti-malarial sesquiterpene lactone derived from Artemisia annua L. (Asteraceae family). One of the most widely used modes of treatment for malaria is an artemisinin-based combination therapy. Artemisinin and its associated compounds have a variety of pharmacological qualities that have helped achieve economic prominence in recent years. So far, research on the biosynthesis of this bioactive metabolite has revealed that it is produced in glandular trichomes and that the genes responsible for its production must be overexpressed in order to meet demand. Using biotechnological applications such as tissue culture, genetic engineering, and bioreactor-based approaches would aid in the upregulation of artemisinin yield, which is needed for the future. The current review focuses on the tissue culture aspects of propagation of A. annua and production of artemisinin from A. annua L. cell and organ cultures. The review also focuses on elicitation strategies in cell and organ cultures, as well as artemisinin biosynthesis and metabolic engineering of biosynthetic genes in Artemisia and plant model systems.

Environmental sustainable mathematically processed UV spectroscopic methods for quality control analysis of remogliflozin and teneligliptin: Evaluation of greenness and whiteness.

Environmental sustainable analytical methods were developed by mathematical modification of UV absorption spectra for quality control study of multicomponent formulations consisting of remogliflozin (REM) and teneligliptin (TEN), with good sensitivity and selectivity. Then analytes were quantified by measuring the peak amplitude of the first derivative spectra at zero crossing points at 230.2 nm and 213.8 nm for REG and TEN in the first derivative method. The second method involves the formation of ratio spectra and taking the absorption difference at two selected wavelengths of peak and trough of a spectrum. In the ratio first derivative method peak amplitudes were measured at 235.2 nm and 259.1 nm for simultaneous quantification of REM and TEN respectively. The fourth method was based on the measurement of the peak amplitude of zero-order spectra of analytes generated from the mixture spectrum by subtraction of a constant from the ratio spectrum followed by multiplication with divisor spectrum, Further, the proposed methods were validated systematically to confirm the linearity, precession, accuracy, sensitivity, and selectivity. Finally, validated UV spectroscopic methods were applied for simultaneous quantification of REM and TEN from formulation, and laboratory mixed solutions and statistically compared with the reported HPLC method. Further, recently developed AGREE, Hexagonal greenness and white analytical chemistry, a whiteness evaluation tools were applied to the proposed UV spectroscopic methods and found to be safer analytical methods, compared to the reported expensive, time-consuming and toxic HPLC method. Hence, proposed UV spectroscopic methods could be used for routine quality control of formulations containing REM and TEN.

Progress Report: Antimicrobial Drug Discovery in the Resistance Era.

Antibiotic resistance continues to be a most serious threat to public health. This situation demands that the scientific community increase their efforts for the discovery of alternative strategies to circumvent the problems associated with conventional small molecule therapeutics. The Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report (published in June 2021) discloses the rapidly increasing number of bacterial infections that are mainly caused by antimicrobial-resistant bacteria. These concerns have initiated various government agencies and other organizations to educate the public regarding the appropriate use of antibiotics. This review discusses a brief highlight on the timeline of antimicrobial drug discovery with a special emphasis on the historical development of antimicrobial resistance. In addition, new antimicrobial targets and approaches, recent developments in drug screening, design, and delivery were covered. This review also discusses the emergence and roles of various antibiotic adjuvants and combination therapies while shedding light on current challenges and future perspectives. Overall, the emergence of resistant microbial strains has challenged drug discovery but their efforts to develop alternative technologies such as nanomaterials seem to be promising for the future.

Formulation and Evaluation of Self-Nanoemulsifying Drug Delivery System Derived Tablet Containing Sertraline.

Being a biopharmaceutics classification system class II drug, the absorption of sertraline from the gut is mainly limited by its poor aqueous solubility. The objective of this investigation was to improve the solubility of sertraline utilizing self-nanoemulsifying drug delivery systems (SNEDDS) and developing it into a tablet dosage form. Ternary phase diagrams were created to identify nanoemulsion regions by fixing oil (glycerol triacetate) and water while varying the surfactant (Tween 80) and co-surfactant (PEG 200) ratio (Smix). A three-factor, two-level (23) full factorial design (batches F1-F8) was utilized to check the effect of independent variables on dependent variables. Selected SNEDDS (batch F4) was solidified into powder by solid carrier adsorption method and compressed into tablets. The SNEDDS-loaded tablets were characterized for various pharmaceutical properties, drug release and evaluated in vivo in Wistar rats. A larger isotropic region was noticed with a Smix ratio of 2:1 and the nanoemulsion exhibited good stability. Screening studies' data established that all three independent factors influence the dependent variables. The prepared tablets displayed optimal pharmaceutical properties within acceptable limits. In vitro sertraline release demonstrated from solid SNEDDS was statistically significant (p < 0.0001) as compared to pure sertraline. Differential Scanning Calorimetry and X-Ray Diffraction data established the amorphous state of the drug in SNEDDS formulation, while FTIR spectra indicate the compatibility of excipients and drug. Pharmacokinetic evaluation of the SNEDDS tablet demonstrated significant increment (p < 0.0001) in AUC0-α (~5-folds), Cmax (~4-folds), and relative bioavailability (386%) as compared to sertraline suspension. The current study concludes that the solid SNEDDS formulation could be a practicable and effective strategy for oral therapy of sertraline.

Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box-Behnken Design and In Vitro Evaluation.

Topical therapy of antifungals is primarily restricted due to the low innate transport of drugs through the thick multi-layered keratinized nail plate. The objective of this investigation was to develop a gel formulation, and to optimize and evaluate the transungual delivery of terbinafine using the constant voltage iontophoresis technique. Statistical analysis was performed using Box-Behnken design to optimize the transungual delivery of terbinafine by examining crucial variables namely concentration of polyethylene glycol, voltage, and duration of application (2-6 h). Optimization data in batches (F1-F17) demonstrated that chemical enhancer, applied voltage, and application time have influenced terbinafine nail delivery. Higher ex vivo permeation and drug accumulation into the nail tissue were noticed in the optimized batch (F8) when compared with other batches (F1-F17). A greater amount of terbinafine was released across the nails when the drug was accumulated by iontophoresis than the passive counterpart. A remarkably higher zone of inhibition was observed in nails with greater drug accumulation due to iontophoresis, as compared to the passive process. The results here demonstrate that the optimized formulation with low voltage iontophoresis could be a viable and alternative tool in the transungual delivery of terbinafine, which in turn could improve the success rate of topical nail therapy in onychomycosis.

Development of Ecofriendly Derivative Spectrophotometric Methods for the Simultaneous Quantitative Analysis of Remogliflozin and Vildagliptin from Formulation.

Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method.

Nanotechnology Integration for SARS-CoV-2 Diagnosis and Treatment: An Approach to Preventing Pandemic.

The SARS-CoV-2 outbreak is the COVID-19 disease, which has caused massive health devastation, prompting the World Health Organization to declare a worldwide health emergency. The corona virus infected millions of people worldwide, and many died as a result of a lack of particular medications. The current emergency necessitates extensive therapy in order to stop the spread of the coronavirus. There are various vaccinations available, but no validated COVID-19 treatments. Since its outbreak, many therapeutics have been tested, including the use of repurposed medications, nucleoside inhibitors, protease inhibitors, broad spectrum antivirals, convalescence plasma therapies, immune-modulators, and monoclonal antibodies. However, these approaches have not yielded any outcomes and are mostly used to alleviate symptoms associated with potentially fatal adverse drug reactions. Nanoparticles, on the other hand, may prove to be an effective treatment for COVID-19. They can be designed to boost the efficacy of currently available antiviral medications or to trigger a rapid immune response against COVID-19. In the last decade, there has been significant progress in nanotechnology. This review focuses on the virus's basic structure, pathogenesis, and current treatment options for COVID-19. This study addresses nanotechnology and its applications in diagnosis, prevention, treatment, and targeted vaccine delivery, laying the groundwork for a successful pandemic fight.