49 research outputs found
Microwave-derivatized enhanced-spectrofluorophotometric characterization of nateglinide-loaded solid dispersion adsorbate and greenness profile assessment of method
No full textNateglinide is an oral meglitinide that treats diabetes. Nateglinide was determined in several commercial formulations using chromatographic and spectrophotometric methods in published research. Quality-by-design approach was applied to develop the in-house nateglinide-loaded Solid Dispersion Adsorbate (SDA) for improving bioavailability and solubility. To determine nanogram-level nateglinide concentration for the in-house developed nateglinide-SDA pharmacokinetics required time-consuming and expensive hyphenated analytical techniques such as LC-MS or UPLC-MS. Hence, a sensitive spectrofluorophotometric method was developed to estimate nateglinide using NBD-Cl (7-chloro-4-nitrobenzoxadiazole) as the fluorophore. Microwave-aided chemical derivatization of nateglinide with NBD-Cl sped up sample analysis. Chemical reaction solvents were eco-friendly to safeguard aquatic life and environment. The chemical process was optimized by quality by design approach using screening design and response surface modelling. The fluorescence intensity of nateglinide was found to be linear over the concentration range of 20–250 ng/mL with a correlation coefficient of 0.9978. The limits of detection and quantification were found to be 10 and 20 ng/mL respectively. Precision and robustness investigations of the spectrofluorimetric method showed less than 2% relative standard deviations. Nateglinide-SDA drug-release study and pharmacokinetics were performed using the sensitive spectrofluorophotometric method. The in-house developed nateglinide-SDA released 95% of the drug in 30 min time duration. In-house-developed nateglinide-SDA has 1.5 times the oral bioavailability of commercial formulations due to in-vivo absorption. The published analytical methods were compared to the enhanced-spectrofluorophotometric method for user-friendliness, efficiency, cost-of-analysis, and environmental friendliness. The proposed sensitive-spectrofluorophotometric method was found to be robust, rapid, eco-friendly, cost-effective, and simple for the estimation of nateglinide.This work was supported by the Researchers Supporting Project number (RSPD2024R726), King Saud University, Riyadh, Saudi Arabia
Cycloartane-type glycosides from Astragalus brachycalyx FISCHER and their effects on cytokine release and hemolysis
No full textTwo new tridesmosidic cycloartane-type triterpene glycosides (1 and 2) were isolated from the methanolic extract of the roots of Astragalus brachycalyx FISCHER (A. brachycalyx) along with ten (3-12) known cycloartanetype triterpene glycosides. Structures of the new compounds were established as 3-O-beta-D-xylopyranosyl-6-O-beta-Dglucopyranosyl- 16-O-beta-D-glucopyranosyl-3 beta, 6a, 16 beta, 24(S)-25-pentahydroxycycloartane (1), 3-O-[a-L-arabinopyranosyl-(1. 2)-beta-D-xylopyranosyl]-6-O-beta-D-glucopyranosyl-16-O-beta-D-glucopyranosyl-3 beta, 6 alpha, 16 beta, 24(S)-25-pentahydroxycycloartane (2), by using 1D and 2D-NMR techniques and mass spectrometry. In vitro immunomodulatory effects and hemolytic activities of the new saponins (1 and 2) and acetylated form of 1 (1a) were studied together with the BuOH and MeOH extracts of Astragalus brachycalyx. The results have proven that tridesmosidic Astragalus cycloartanes are noteworthy immunomodulatory compounds via induction of cytokine production, namely IL-2 and IFN-gamma. The test compounds also resulted slight hemolysis at very high doses substantiating a safer profile compared to the positive control QS-21.Ege University Research FoundationEge University [15-FBE-001]The authors gratefully acknowledge to the financial support of Ege University Research Foundation (15-FBE-001) for the finical support and thank Prof. Dr. Ali Asghar Maassoumi for the identification of the plant material, and special thanks to NMR operators of both Ege University and Prince Sattam bin Abdulaziz University namely Salih Gunnaz and Anzarul Haque, respectively
Surface-engineered Niosomes of Esculin Hydrate for the management of depression via intranasal route: Optimization, In vitro, Ex vivo and pharmacokinetic assessment
No full textPresent research explored the potential of surface-engineered niosomes of Esculin hydrate (ESCH), coated with chitosan, as a novel approach for managing depression through intranasal administration. Formulation optimization was done by Design Expert® software, employing Central Composite Rotatable Design (CCRD) to investigate the impact of independent factors on dependent variables. Characterization of the chitosan-coated ESCH-loaded niosomes (Ch-ESCH-Ns) included the assessment of vesicle-size (190.3 nm), polydispersity-index (PDI; 0.243), zeta potential (ZP, +27.5 mV), and surface morphology by TEM. In vitro release and ex vivo permeation studies were performed to evaluate the formulation's performance compared to the pure drug suspension (ESCH-SUSPN), revealing sustained drug release (89.2 %) with increased drug permeation (353.1 μg/cm2) at 24 h from Opt-Ch-ESCH-Ns. Antioxidant properties were assessed by ABTS assay, demonstrating the formulation's ability to mitigate oxidative stress, with Opt-Ch-ESCH-Ns exhibiting 79.8 % scavenging activity as compared to 52.6 % for ESCH-SUSPN. Confocal laser scanning microscopy revealed an efficient penetration of Opt-Ch-ESCH-Ns that reaches to 45 μm deep into nasal mucosa layer, indicating a promising carrier for intranasal delivery of ESCH to cross blood-brain barrier and manage neurological disorders. Un-noticeable changes in physical appearance, phase separation, size, PDI and ZP, confirmed 6-months storage stability of Opt-Ch-ESCH-Ns at 4 °C and 25 °C. The intranasal Opt-Ch-ESCH-Ns has shown substantially increased pharmacokinetics in plasma (Cmax 18.98 μg/mL; AUC0-t 152.05 μg/mL; MRT0-∞ 9.5 h; t1/2 of 6.1 h) and brain (Cmax 27.89 μg/mL; AUC0-t 334.67 μg/mL; MRT0-∞ 15.9 h and t1/2 of 10.5 h) of rats, which significantly improved the neuroprotection against the induced neurotoxicity as compared to oral ESCH-SUSPN. Thus, this study highlighted the potential of Opt-Ch-ESCH-Ns as a promising strategy for enhancing the therapeutic efficacy of ESCH in depression management via intranasal delivery, which requisite the further clinical investigations
Red, green, and blue model assessment and AQbD approach to HPTLC method for concomitant analysis of metformin, pioglitazone, and teneligliptin
No full textBackground
The CDSCO of India has authorized a combination of metformin hydrochloride, teneligliptin hydrochloride, and pioglitazone hydrochloride for the treatment of insulin-independent diabetes. For the purpose of estimating metformin, teneligliptin, and pioglitazone combinations as well as individual commercial formulations, there are a plethora of publicly accessible chromatographic techniques. More importantly, the development of these chromatographic procedures has included the use of chemical solvents that are dangerous to both animals and the environment.
Objectives
However, to date, there has been no documented chromatographic technique that can concomitantly estimate various commercial formulations of drugs under study employing a uniform chromatographic condition and environmentally friendly solvents. In order to concomitantly estimate drugs under study utilizing unified chromatographic conditions, a green HPTLC method was developed.
Method
The AQbD approach was used to carry out the method development. To determine the most important method parameters and response variables, the analytical risk assessment was conducted using the risk priority number ranking and screening approach. Critical method parameters and response variables were modeled using the response surface modeling approach, which relies on the central composite design. Optimal ranges for the intended method operable design region were determined, and control strategy was framed. The chromatographic separation was carried out on preparative TLC plate precoated with silica gel G-60 F254 using 1.0%W/V ammonium acetate in ethanol: water: triethylamine (6.5:0.4:0.6, V/V) as mobile phase. The detection of the anti-diabetic drugs under study was carried out at 267 nm wavelength.
Results
The linearity of metformin, teneligliptin, and pioglitazone was found to be 5000–25000 ng/band, 200–1000 ng/band, and 150–750 ng/band, respectively. The %RSD for robustness and precision study was found to be less than 2.0%. The %recovery of method was found to be 98–102%. The assay results were shown to be in compliance with respective labeled claims of anti-diabetic medications when the suggested method was used for concurrent analysis of several formulations and combinations of drugs under study.
Conclusion
The suggested technique was evaluated utilizing red–green–blue model scoring tools. The suggested technique was determined to be precise, accurate, rapid, cost-effective, and easy to apply for the estimation of drugs under study
Failure Mode Effects Analysis and Design of Experiments to Sensitive and Sustainable Microwave-Aided Spectrofluorophotometric Estimation of Teneligliptin and Method's Chlor-Tox Scale and Blue Applicability Grade Index Assessment
No full textTeneligliptin hydrobromide hydrate is efficiently controls blood sugar levels while minimizing the risk of hypoglycemia. Determination of teneligliptin in commercial formulations and biological-fluids has been documented in literature using a plethora of chromatographic, spectrophotometric, and hyphenated methods and they required toxic organic solvents. But, there was no published spectrofluorophotometric technique for teneligliptin estimation. Hence, microwave-aided spectrofluorophotometric method was developed to estimate teneligliptin with using green solvents and 7-chloro-4-nitrobenzoxadiazole as a fluorescent probe. An integrated approach of white analytical chemistry and analytical quality by design was used to estimate teneligliptin in a robust, accurate, and precise manner. The failure mode effect analysis was used to identify the critical analytical method parameters and response variables. The design of experiments was used to carry forward the important analytical method parameters and response variables for response surface modeling. The proposed spectrofluorophotometric method was applied to evaluate commercially available formulations and investigate the pharmacokinetics of teneligliptin–loaded nano-carriers that was developed in-house. The fluorescent product that was derivatized using microwaves was separated and studied using mass spectrometry. After greenness and whiteness profile assessment, researchers discovered that the suggested approach to teneligliptin estimate was eco-friendly, precise, robust, rapid, economical, and easy to apply
A Selective and Accurate LC-MS/MS Method for Simultaneous Quantification of Valsartan and Hydrochlorothiazide in Human Plasma
No full textThe fixed dose combination of valsartan (VAL) and hydrochlorothiazide (HCTZ) is the most commonly prescribed medicine for the effective treatment of hypertension. In this study, a simple sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantitation of VAL and HCTZ in human plasma by using irbesartan (IRB) and hydroflumethiazide (HFMZ) as their specific internal standards (ISs). HLB cartridge-based solid-phase extraction was used for the extraction of analytes and ISs. The chromatographic separation was achieved on Lichrocart RP Select (125 × 4 mm), 5 nm with the mobile phase composition of acetonitrile: 10 mM ammonium acetate buffer: 95:05, v/v, at flow rate of 0.5 mL/min. The turbo ion electrospray ionization in negative mode was used as ion source for the sample ionization. The precursor to product ion transitions were 434.10 > 179.10 (VAL), 295.70 > 204.90 (HCTZ), 427.10 > 192.90 (IRB), and 329.90 > 302.40 (HFMZ) for detection and quantification of analytes and their ISs. The retention times of VAL and HCTZ were 1.90 min and 2.30 min, respectively. The range for the calibration curves of VAL and HCTZ were 50.2–6018.6 ng/mL and 1.25–507.63 ng/mL, respectively, with good linearity having correlation coefficient values of ≥0.995 for both VAL and HCTZ. All validation parameter results (selectivity, precision and accuracy, matrix effects and stabilities) were within the acceptable range as per USFDA guideline for bioanalytical method validation. The intra-day and inter-day accuracy data for VAL were within the range of 105.68–114.22% and 98.41–108.16%, respectively, whereas for HCTZ they were 87.01–101.18% and 95.16–99.37%, respectively. The ion suppression effects produced for VAL and ion enhancement effects produced for HCTZ were insignificant according to the proposed sample cleanup procedure. The developed LC-MS/MS method was successfully applied to bioequivalence study on healthy volunteers
Targeting protein receptors and enzymes for precision management of urolithiasis: A comprehensive review
No full textUrolithiasis, characterized by the formation of solid crystalline structures within the urinary tract, presents a significant global health burden with high recurrence rates and limited treatment efficacy. Recent research has identified various protein receptors and enzymes implicated in the pathogenesis of urolithiasis, offering potential targets for therapeutic intervention. Protein receptors such as the calcium-sensing receptor and vasopressin V2 receptor play crucial roles in regulating urinary calcium excretion and water reabsorption, respectively, influencing stone formation. Additionally, modulation of receptors like the angiotensin II receptor and aldosterone receptor can impact renal function and electrolyte balance, contributing to stone prevention. Furthermore, enzymes such as urease inhibitors and xanthine oxidase inhibitors offer targeted approaches to prevent the formation of specific stone types. This review discusses the potential of targeting these receptors and enzymes for the treatment of urolithiasis, exploring associated drugs and their mechanisms of action. Despite promising avenues for personalized and precision medicine approaches, challenges such as the need for robust clinical evidence and ensuring cost-effectiveness must be addressed for the translation of these interventions into clinical practice. By overcoming these challenges, receptor-targeted therapies and enzyme inhibitors hold promise for revolutionizing the management of urolithiasis and reducing its global burden.This work was supported by Qatar University through a National Capacity Building Program Grant (NCBP) [
QUCPCAM-22/24-463]. The publication of the article was financially supported by the Qatar National Library. Statements made herein are solely the responsibility of the authors
A novel mucoadhesive paliperidone-nanoemulsion developed using the ultrasonication method in the treatment of schizophrenia
No full textAim: To develop paliperidone mucoadhesive-nanoemulsion (PLP-NE) to enhance brain bioavailability. To evaluate comparative effects of PLP-NE and CS-PLP-NE in the treatment of schizophrenia, followed by a toxicity study of opt-NE. Material and methods: Oil: oleic acid, surfactant: Tween-80, and co-surfactant: Labrasol were chosen based on the solubility and maximum nanoemulsion area. The ultrasonication technique was applied with the aqueous micro titration method for the development of PLP-NE. The optimization of the method for the excellent PLP-NE was performed using a central composite design based on a five-factor and four-level. Oil (% v/v), Smix (v/v%), ultrasonication intensity in percentage, ultrasonication time in minutes, and temperature (°C) were optimized and used to the independent variables. Results: The parameters i.e., oil (5%), Smix (10%), ultrasonication time (5.0 min), ultrasonication intensity (25%), and temperature (38 °C) were optimized and used as independent and dependent variables for the development of novel PLP-NE. Based on experimental data, the dependent variables, i.e., globule size (53.90 ± 4.01 nm), % transmittance (92.56% ± 1.06%), PDI (0.218 ± 0.007), and zeta potential (−11.60 ± 0.031 mV), were determined. The smooth near about spherical shaped of PLP-NE globules with, refractive index i.e., 1.62 ± 0.021, viscosity: 39 ± 6 cp with the pH: 7.40 ± 0.089, and content of drug (97.98 ± 0.39%) for optimized-PLP-NE. The optimized PLP-NE with oleic acid, Tween-80, and Labrasol was used to improve brain bioavailability with good permeation via the intranasal route. CS-PLP-NE yielded good mucoadhesive property results compared to paliperidone-nanoemulsion, and PLP-S containing a 0.751 minutes retention time with their deuterated-IS (0.806 min) and m/z of 427.2/207.2 with IS (m/z: 431.2/211.2) for PLP and PLP-IS. A calibration curve was plotted with a linear range of 1-2000 ng mL−1 with inter- and intraday accuracy (97.03-99.31%) and precision (1.69-50.05%). The results of AUC(0-24) and Cmax for PLP were found to be highly significant (p < 0.001) as an improvement of brain bioavailability in rats via intranasal delivery of CS-PLP-NE. Furthermore, the locomotion test, social interaction, and forced swimming test (forced swimming, climbing, and immobility) of a mucoadhesive CS-PLP-NE (intranasally) provided highly significant results with the improvement of behavioral analysis when compared to the PLP-NE and PLP-S studies. Conclusion: CS-PLP-NE (i.n.) showed highly significant results, i.e., p < 0.001 for the improvement of bioavailability of the brain in the treatment of schizophrenia. Optimized-mucoadhesive-CS-based-PLP-NE is safe and shows no toxicity.This study is supported via funding from “Prince Sattam Bin Abdulaziz University Project Number (PSAU/2024/R/1445)”
Development of novel nanoemulsion of pioglitazone used in the treatment of diabetes and its gel form for the treatment of skin diseases
No full textPioglitazone (PGL), an antidiabetic drug within the thiazolidinedione class, is utilized in managing type-2-diabetes-mellitus. Additionally, it has been observed to exhibit therapeutic effects on various inflammatory markers. PGL falls under BCS Class II, which is defined by its low water solubility and slow dissolution rate. The dual aim of our study was to optimize an oral as well as topical PGL-loaded nanoemulsion (PGL-NE) in order to enhance their bioavailability orally as well as topically. Using the Box–Behnken Design Expert software, Pioglitazone-loaded nanoemulsions (NanoE1 to NanoE17) were optimized. The ultrasonication method was employed following excipients-screening and the preparation of PTPD. The optimized nanoformulation (NanoE13) was determined based on its particle size (137.7 ± 7.92 nm), %Transmittance (91.07 ± 1.03), and PDI (0.221 ± 0.004). NanoE13 exhibited sustained drug release, adhering to the Korsemeyer-Peppas model. When converted into a gel (PGL-NE-Gel), it enhanced permeation of the skin and topical bioavailability. The results of dermatokinetic demonstrated a significant i.e., p˂0.001 increase in CSkinmax & AUC0–8h in skin treated with the optimized PGL-NE-Gel compared to PGL-NE and conventional PGL gel. After 2 weeks, reductions of 40.06 %, 27.34 %, and 37.45 % were observed for diabetic control, PGL-S, and PGL-NE, respectively. PGL-NE also significantly lowered the levels of blood-glucose i.e., p < 0.05 as compared to the diabetic-control -group throughout the experiment. We successfully developed a novel PGL-NE and PGL-NE-Gel, which enhanced the solubility, skin permeation, and bioavailability of Pioglitazone for both oral and topical applications.This study received financial support from “Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia, project number PSAU/2024/R/1446”
Solubility of a poorly soluble immunosuppressant in different pure solvents: Measurement, correlation, thermodynamics and molecular interactions
No full text
