Telmisartan Research Articles

Specialized greenness sustainability tools for evaluation of the spectrophotometric methodologies greenness: spectral signal manipulation for resolving the interfering telmisartan and metoprolol succinate spectra in their bulk and pharmaceutical formulation.

Hypertension is a leading cause of cardiovascular mortality, often accompanied by complications such as arrhythmia and stroke. This silent killer requires a multifaceted pharmacological approach for effective management. This article presents new, environmentally friendly spectrophotometric methods for simultaneous quantification of telmisartan (TER) and metoprolol succinate (MTR) in laboratory prepared mixtures and pharmaceutical formulations. The suggested methodologies include the following: area under the curve method (AUC) utilizing area at specific wavelength ranges 228 -233 nm (λ1 – λ2) and 240 – 245 nm (λ3 – λ4) for each analyte and Fourier self-deconvolution method (FD) depending on built-in function to address spectral interferences. In addition, the induced dual wavelength method (IDWL) employing equality factors to obtain absorbance differences at designated wavelengths, ratio difference method (RD) utilizing divisor-based ratio spectra where the utilized divisors were TER 40 μg/mL and MTR 90 μg/mL, and ratio derivative method (RDV) generating spectra through first derivative application that was measured at 266 nm and 246 nm for TER and MTR, respectively. These methods offer green alternatives for the accurate and precise determination of TER and MTR with exceptional linearity of 3 – 45, and 15 – 200 μg/mL for TER and MTR, respectively. Furthermore, the methods showed a coefficient of determination exceeding 0.9995 and good detection and quantification levels. A comprehensive greenness assessment, employing five distinct evaluation tools, confirmed the reduced environmental impact of the proposed methods in terms of waste generation, chemical consumption, and instrument safety. Successful analysis of pharmaceutical formulations and laboratory prepared mixtures containing different TER and MTR ratios confirmed the validity of the proposed methods. Standard addition studies further supported these findings, and the statistical results were comparable to those obtained using a reference method.

Complexation of telmisartan with cyclodextrins as a tool of solubility enhancement: A comparative analysis of influence of the cyclodextrin type and method of solid dispersion preparation

Cardiovascular telmisartan (TMS) was complexed with modified cyclodextrins (CD) aiming at improvement of its poor solubility which results into low bioavailability. Inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) in liquid and solid state was evaluated for first time. Phase solubility isotherm diagrams of TMS versus the CD concentration were plotted in a buffer pH 7.4. It was found that TMS/CD complexes are formed in solution in an equimolar stoichiometric ratio of 1:1. The aqueous solubility of TMS with the addition of 0.05 mol·L−1 HP-β-CD increased by 23 times and was 38.9·10−5 mol·L−1, and the presence of the same amount of SBE-β-CD in solution increased the solubility of the drug by 7 times, reaching a value of 12.6·10−5 mol·L−1.The binding constants were found to 468 and 114 L·mol−1 for HP-β-CD and SBE-β-CD, respectively. Novel solid forms of TMS with both CDs were prepared using the grinding and evaporation approaches. Successful formation of supramolecular TMS/HP-β-CD and TMS/SBE-β-CD solid complexes was confirmed by FTIR, PXRD, DSC, TGA and SEM. The residual crystallinity of all obtained solid dispersions of TMS/CD did not exceed 10 %. Supersaturation was observed during the dissolution of all the solid complexes. The grinding technique was found to be more advantageous as it ensured the biggest improvement of the drug maximum concentration in the aqueous solution: the TMS solubility in the TMS/HP-β-CD(gr) and TMS/SBE-β-CD(gr) solid complexes increased by 27 and 33 times, respectively. Besides, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG) were tested as crystallization inhibitors. Addition of 1 wt% PVP as a stabilizer is a promising approach for the preparation of TMS pharmaceutical formulations with improved bioavailability.

Atorvastatin and telmisartan do not reduce nasopharyngeal carriage of SARS-CoV-2 in mild or moderate COVID-19 in a phase IIb randomized controlled trial

Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥ 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ≥ 40 and C-reactive protein < 27 mg/L. We randomized 294 patients: 96 to LPVr, 100 to LPVr + TLM, 98 to LPVr + ATV arms. Baseline characteristics were well balanced between arms. In the primary analysis (missing = failure), 46% patients in the LPVr arm reached viro-inflammatory success at day 11 vs 43% in the LPVr + TLM arm (p = 0.69) and 43% in the LPVr + ATV arm (p = 0.68). The median time from baseline to resolution of COVID-19 related symptoms was not different between arms. Nine patients were hospitalized: 2 in the LPVr arm, 5 in the LPVr + TLM arm and 2 in the LPVr + ATV arm and 4 patients died. Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard LPVr treatment is not associated with a better virological or clinical outcome.Trial registration: NCT04466241, registered on 10/07/2020

Transformation of sartan blood pressure regulators by ferrate(VI) and its activation systems: Kinetics and mechanisms

With the increasing number of patients diagnosed with hypertension, the annual consumption of sartan drugs has surged, resulting in their ubiquitous detection in aquatic environments. This increases concerns about their environmental persistence and unexpected toxicity. This study explores the applications of ferrate(VI) (Fe(VI)) in removing sartan blood pressure regulators (losartan (LOS), valsartan (VAL), and telmisartan (TEL)). Results demonstrate that sartans could be effectively removed by Fe(VI). Oxidation of LOS by Fe(VI) was pH-dependent at pH 7.0–9.0, with HFeO4– dominating the reaction. The second-order rate constants (kapp) of LOS with Fe(VI) decreased with increasing solution pH, and kapp was calculated to be 148.37 M−1 s−1 at pH 8.0. Furthermore, the Fe(VI)-Fe(III), Fe(VI)-S(IV), and Fe(VI)-S2O32– systems demonstrated the enhancement for the elimination of LOS, while the Fe(VI)–HCO3– system inhibited the reaction. Oxidizing product (OP) analysis suggested that the major transformation patterns of LOS, VAL, and TEL treated by Fe(VI) and its activation systems included oxidation, imidazole ring cleavage, cyclization, N-dealkylation, and bond cleavage. Multiple OPs were estimated to be more persistent and mobile than parent sartans, while their toxicity toward aquatic organisms might be several times lower than those of their parents. Overall, this study elucidates the oxidizing feasibility of Fe(VI) and related activation systems to eliminate sartans in water treatment.

A sustainable HPLC method coupled with diode array detection for versatile quantification of telmisartan, chlorthalidone and amlodipine in a fixed-dose antihypertensive formulation and dissolution studies

Cardiovascular diseases, especially hypertension, stand as prominent contributors to global mortality. Hypertension, often referred to as a silent killer syndrome, necessitates the use of multiple medications for effective control and management. A new environmentally friendly HPLC–DAD method is introduced in this study for the concurrent analysis of telmisartan (TEL), chlorthalidone (CHT) and amlodipine besylate (AML), in both pure forms and combined pharmaceutical dosage form. An isocratic elution mode was employed to achieve chromatographic separation, utilizing an Inertsil C18 column (250 × 4.6 mm, 5.0 µm) and a mobile phase mixture of acetonitrile and phosphate buffer (pH 3.0 ± 0.1) with ratio of 35:65, v/v. The separation was achieved within 10 min at a flow rate of 1.0 mL/min. The proposed method's validation was carried out following the guidelines outlined by the International Council for Harmonisation (ICH). The achieved linearity range was 1.0–140.0 μg/mL for TEL and 1.0–100.0 μg/mL for CHT and AML with quantification limits of 0.061, 0.177, and 0.313 μg/mL for TEL, CHT, and AML, respectively. The fixed combination tablet dosage form demonstrated acceptable release profile, as indicated by the in-vitro dissolution studies. The studied dissolution media were phosphate buffer pH 7.5, 0.01 N HCl, and water, utilizing a USP type II apparatus at 37 ± 0.5 °C with a stirring rate of 75 rpm. The proposed method was applied successfully for the quality assessment of Telma-ACT® Tablets with good precision and accuracy. Various tools were used for evaluating the level of greenness, including Green Analytical Procedure Index (GAPI), Analytical Greenness Metric for Sample Preparation (AGREEprep), Analytical Eco-Scale (AES), and Analytical Method Greenness Score (AMGS). These tools had confirmed the eco-friendliness of the proposed method. Additionally, the newly introduced White Analytical Chemistry (WAC), and the Blue Applicability Grade Index (BAGI) have been specifically developed to evaluate the sustainability and the applicability of the method.

HPTLC – densitometric method of analysis for estimation of efonidipine hydrochloride and telmisartan used in treatment of hypertension

Precise, accurate, and sensitive high performance thin layer chromatographic method has been developed and validated for simultaneous determination of efonidipine hydrochloride (EFD) and telmisartan (TEL) in a tablet dosage form which is used in treatment of hypertension. The proposed method used aluminum plates pre-coated with silica gel 60 F254 as a stationary phase and n-butanol: toluene: acetic acid (3:7:0.2, v/v/v) as a mobile phase for separation purpose. Compact spots of TEL and EFD were obtained at Rf 0.73 and 0.37, respectively. Densitometric detection was carried out at 299 nm in UV. Linear responses were shown by the detector over the range of 200–1200 ng/band for both drugs. The proposed method was validated as per ICH guidelines. The method was successfully applied for estimation of both drugs in tablet formulations. Forced degradation study was carried and efonidipine was found to be susceptible to base hydrolysis and oxidative stress degradation while TEL was stable in acid-base hydrolysis, oxidative stress, dry heat and photo stability testing conditions. The developed method can be used for the analysis of stability samples. Greenness assessment of developed method was performed using AGREE software. The method was found to be greener having greenness score of 0.69.

SPHERICAL AGGLOMERATION OF TELMISARTAN - AN APPROACH TO IMPROVE PHYSICOCHEMICAL PROPERTIES

The study explains the preparation of spherical agglomerates (SA) of telmisartan (TLS), a BCS class II drug used to improve it’s physicochemical and bulk properties. Drugs of this class could potentially exhibit dissolution rate limited absorption. TLS spherical agglomerates were designed using hydrophilic polymer (PVP K-30), dimethyl formamide (DMF), water and ethyl acetate (bridging liquid) by solvent change method and evaluated for micromeritic properties. The SA were characterized by particle size determination, FTIR, PXRD and SEM. The results of micromeritic studies indicated that SA showed improved flow properties due to their spherical shape and bigger size. Absence of strong interaction at molecular level and alteration in the crystal structure of TLS with modification in crystallinity was confirmed by FTIR and PXRD respectively. TLS solubility characteristics were improved by this approach.

Telmisartan loaded lipid nanocarrier as a potential repurposing approach to treat glioma: characterization, apoptosis evaluation in U87MG cells, pharmacokinetic and molecular simulation study

The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized. In vitro anticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC50 for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC, V ss, MRT with lower Clt for TLNs suggesting improved bioavailability, in vivo residence and sustained drug availability than free TS administration. Docking studies rationalized in vitro/in vivo results as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further, in vivo studies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.

Influence of angiotensin II and telmisartan on in vivo high-resolution renal arterial impedance in rats.

Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high-resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three-element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10-1) min·mL-1. ANG II significantly increased the slope by 0.72 ± 0.29 (× 10-1) min·mL-1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10-1) mmHg·min·mL-1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10-1) mmHg·min·mL-1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANG II or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature.NEW & NOTEWORTHY This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II.

Enhancing simultaneous determination of some angiotensin II receptor antagonists and amlodipine in plasma using HPTLC with fluorescence densitometry: Independent fluorescence detection of the co-administrative drugs in the mixture across various pH conditions

A novel and highly sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated to quantify a combination of five pharmaceutical mixtures spiked to human plasma. The compounds comprised Amlodipine (AML) along with five angiotensin II receptor antagonist drugs (AIIRAs), namely Olmesartan (OLM), Telmisartan (TLM), Candesartan (CAN), Losartan (LOS), and Irbesartan (IRB). HPTLC was performed on silica gel 60 F254 plates using a mobile phase of Toluene: ethyl acetate: methanol: acetone: acetic acid (6:1.5:1:0.5:1, v/v/v/v/v). In a pioneering move, a reflectance/fluorescence detection mode was employed to identify two concurrently administered drugs at different pH levels for the first time. This method utilized the same chromatographic system, incorporating a specific measurement for AML at a neutral medium to achieve its maximum fluorescence at a 360 nm excitation wavelength, and measuring emission using a 540 nm optical filter. The process involved obtaining a very low fluorescence response from AIIRA. Subsequently, to enhance AIIRA’s fluorescence, the plate was sprayed with perchloric acid to transition to a strong acidic medium, ultimately attaining the maximum fluorescence of AIIRA using various excitation wavelengths and a 400 nm emission filter. Through this strategic process, we could optimize the fluorescence signals of both drugs, thereby elevating the sensitivity of detection for this drug combination. AML demonstrated a linear range of 18–300 ng/band, while AIIRAs drugs exhibited a linear range of 6–150 ng/band. The method satisfied the International Conference on Harmonization (ICH) criteria for recovery, precision, repeatability, and robustness, showcasing exceptional sensitivity. The approach was successfully applied to quantify AML and AIIRAs drugs in both bulk drug and plasma samples, achieving high recovery percentages and minimal standard deviations.

Perturbations of Telmisartan Alone and in Combination with Ranolazineor Dapagliflozin on the Amplitude and Gating of Voltage-gated Na + Current in Neuroblastoma Neuronal Cells.

A recent study investigated the correlation between telmisartan (TEL) exposure and Alzheimer's disease (AD) risk among African Americans (AAs) and European Americans. Their findings indicated that moderate-to-high TEL exposure was linked to a decreased incidence of AD among AAs. These results suggest a potential association between TEL and a reduced risk of AD specifically within the AA population. Here, we investigated the effects of TEL, either alone or in combination with ranolazine (Ran) or dapagliflozin (Dapa), on voltage-gated Na + currents ( INa ) in Neuro-2a cells. TEL, primarily used for treating hypertension and cardiovascular disorders, showed a stimulatory effect on INa , while Ran and Dapa reversed this stimulation. In Neuro-2a cells, we demonstrated that with exposure to TEL, the transient ( INa(T) ) and late ( INa(L) ) components of INa were differentially stimulated with effective EC 50 's of 16.9 and 3.1 μM, respectively. The research implies that TEL's impact on INa might be associated with enhanced neuronal excitability. This study highlights the complex interplay between TEL, Ran, and Dapa on INa and their potential implications for AD, emphasizing the need for further investigation to understand the mechanisms involved.

Effect of irradiated nonionic surfactant on drug-protein binding

In this work, the effect of γ-irradiated surfactants on drug–protein binding has been assessed. Irradiated aqueous solutions of Pluronic F-127, Pluronic L-35, Tween 20, and Tween 80 surfactants were used. Gamma irradiation was carried out for three different doses, to these four surfactants viz., 6, 30, and 36 kGy. Two drugs, Ornidazole (ONZ) and Telmisartan (TMS) were used for the binding study. The effect of four irradiated surfactants in the presence of drug – Bovine serum albumin (BSA) protein was analyzed. The drug solutions in methanol-aqueous media were combined with BSA in the initial step. In the next two succeeding steps, drug–BSA interaction in the presence of unirradiated and irradiated surfactants were carried out. The results of drug-BSA due to addition of irradiated and unirradiated surfactants were compared. The interaction processes were assessed through UV Spectroscopy, DLS, zeta potential, turbidity, and docking studies. Improved binding was observed for both the drugs and four surfactants for irradiated surfactants as determined from the binding constant values using UV spectroscopic studies. The DLS measurements demonstrated no general trend of increase or decrease in micellar size with absorbed dose. The binding and change in the size of micelles were observed to be highly drug and surfactant-specific. Among the four surfactants, irradiated Pluronic F-127 showed higher binding affinity. To the best of our knowledge, this is the first report on the effect of γ-irradiated surfactant on drug–BSA interaction. This can be applied to other drug–protein systems to tune their interaction to the required level. Communicated by Ramaswamy H. Sarma

Multicomponent Amorphous Solid Forms of Telmisartan: Insights into Mechanochemical Activation and Physicochemical Attributes.

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.

Upregulation, Functional Association, and Correlated Expressions of TRPV1 and TRPA1 During Telmisartan-Driven Immunosuppression of T Cells

ABSTRACT TRPV1 and TRPA1, are known to be functionally expressed in T cells, where these two channels differentially regulate effector immune responses. Telmisartan (TM), an anti-hypertension drug, has been recently repurposed to suppress various inflammatory responses. However, the possible involvement of TRP channels during TM-driven suppression of T cells responses has not been explored yet. In this study, we investigated the potential role of TRPV1 and TRPA1 during TM-driven immunosuppression of T cells in vitro. We observed a significant elevation of both TRPV1 and TRPA1 during TM-induced immunosuppression of T cells.We found that TRPA1 activation-driven suppression of T cell activation and effector cytokine responses during TM treatment is partially, yet significantly overridden by TRPV1 activation. Moreover, the expressions of TRPV1 and TRPA1 were highly correlated in various conditions of T cell. Mechanistically, it might be suggested that TRPV1 and TRPA1 are differentially involved in regulating T cell activation despite the co-elevation of both these TRP channels’ expressions in the presence of TM. T cell activation was delineated by CD69 and CD25 expressions along with the effector cytokine levels (IFN-γ and TNF) in TM-driven suppression of T cell. These findings could have broad implications for designing possible future immunotherapeutic strategies, especially in the repurposing of TM for T cell-TRP-directed immune disorders.

Development of Telmisartan Nanocrystal-Based Dissolving Microneedle for Brain Targeting via Trigeminal Pathway: A Potentially Promising Treatment for Alzheimer's with an Improved Pharmacokinetic Profile.

Telmisartan (TMN), an angiotensin receptor blocker (ARB) drug, is being considered as an alternative therapy for Alzheimer's disease (ALZ). However, when taken orally, its low water solubility leads to a low bioavailability and brain concentration. To overcome this problem, TMN was formulated as nanocrystals (NC), then incorporated into dissolving microneedles (DMN) to enhance drug delivery to the brain via the trigeminal route on the face. TMN-NC was formulated with 1% PVA using the top-down method and stirred for 12 h, producing the smallest particle size of 132 ± 11 nm and showing a better release profile, reaching 89.51 ± 7.52% (2 times greater than pure TMN). TMN-NC-DMN with a combination of 15% PVA and 25% PVP showed optimal mechanical strength and penetration ability; they could dissolve completely within 15 min, and their surface pH was safe for the skin. The permeation test of TMN-NC-DMN showed the highest concentration, reaching 285.80 ± 32.12 μg/mL, compared to TMN-DMN and patch control, which only reached 87.17 ± 11.24 and 94.00 ± 11.09 μg/mL, respectively. The TMN-NC-DMN combination showed better bioavailability and was found to be well-delivered to the brain without any irritation to the skin. Pharmacokinetic parameters had a significant difference (p > 0.05) compared to other preparations, making it a promising treatment for ALZ.

QUALITY BY DESIGN SUPPORTED CONSTRUCTION OF ORAL FAST-DISSOLVING FILMS FOR TELMISARTAN: RECONNOITERING THE QUALITY ATTRIBUTES

Objective: The angiotensin II receptor antagonist telmisartan (TMS) is often used to treat hypertension. The BCS class II antihypertensive drug TMS has a low solubility, poorly absorbed when taken orally. The goal of this study was to formulate an oral fast-dissolving film (OFDF) of TMS. In recent years, the concept of a rapidly dissolving dosage form as an innovative delivery system has gained popularity. By decreasing dosing frequency, maximize therapeutic effectiveness, bioavailability, and stability. It will also prevent the drugs from being metabolized in the first place. This technique allows for faster drug absorption from the gastrointestinal tract (GIT), which might result in a more rapid onset of action. Methods: An experimental design known as Box-Behnken was employed to optimize a OFDF. Mango kernel (100-300 mg), maltodextrin (200-350 mg), and propylene glycol (PG) (15-30%) were chosen as independent variables with the highest preference. Included measurements of T5 tensile strength, disintegration time, folding endurance, elongation, and drug release efficiency as dependent variables. Results: The physical properties of the films were found to be satisfactory, and Fourier transform infrared (FTIR) analysis failed to detect any drug-polymer interaction. F4 was found to have the greatest bioadhesive strength of 49.82 gm and the longest ex-vivo mucoadhesion duration of 189 min. A higher concentration of mango kernel in the formulation resulted in a greater rate of drug release. More than 60% of the drug was discharged within 10 min. Conclusion: The oral mucosa of a rat was used for ex-vivo for irritation studies. Based on the pharmacokinetic plasma parameters, which is made into quick-dissolving films that are taken by mouth, is much better absorbed than aqueous suspensions. Studies of the enhanced formulation's stability showed that F4 may be stored for up to three months without deterioration.

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.

Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan.

Telmisartan (TEL) is a promising antihypertensive agent among other angiotensin receptor blockers. However, its oral application is limited by its poor water solubility. This study presents the successful utilization of biomaterial-based hydrogel-forming microneedles integrated with a direct compressed tablet reservoir (HFMN-DCT) for the transdermal delivery of telmisartan in the treatment of hypertension. The combination of PVP, PVA, and tartaric acid was used in the HFMN formulation. A range of cross-linking temperatures and times were employed to optimize the characteristics of the HFMN. The HFMN exhibited excellent swelling capacity, mechanical strength, and insertion properties. Additionally, the poorly soluble characteristic of TEL was improved by the inclusion complex formulation with β-cyclodextrin (βCD). Phase solubility analysis showed an Ap-type diagram, indicating a higher-order complex between TEL and βCD, with respect to βCD. A ratio of TEL:βCD of 1:4 mM demonstrates the highest solubility enhancement of TEL. The inclusion complex formation was confirmed by FTIR, XRD, DSC, and molecular docking studies. A significantly higher release of TEL (up to 20-fold) from the inclusion complex was observed in the in vitro release study. Subsequently, a DCT reservoir was developed using various concentrations of sodium starch glycolate. Essentially, both the HFMN and DCT reservoir exhibit hemocompatibility and did not induce any skin irritation. The optimized combination of the HFMN-DCT reservoir showed an ex vivo permeation profile of 83.275 ± 2.405%. Notably, the proposed system showed superior pharmacokinetic profiles in the in vivo investigation using male Wistar rats. Overall, this study highlights the potential of HFMN-DCT reservoir systems as a versatile platform for transdermal drug delivery applications.

Encapsulation of telmisartan inside insulinoma-cell-derived extracellular vesicles outperformed biomimetic nanovesicles in modulating the pancreatic inflammatory microenvironment.

Diabetes mellitus (DM) is a chronic metabolic condition, characterized by hyperglycaemia, oxidative imbalance, pancreatic β-cell death, and insulin insufficiency. Angiotensin II (Ang II) increases oxidative stress, inflammation, and apoptosis, and Ang II type 1 receptor (AT1R) blockers (ARBs) can ameliorate inflammatory response and oxidative stress. However, like other small-molecule drugs, free ARBs show poor in vivo efficacy and dose-limiting toxicities. Hence, in this study, we developed nano-formulations of telmisartan (TEL), an ARB, by encapsulating it inside a murine insulinoma cell-derived extracellular vesicle (nanoTEL) and a bio-mimetic lipid nanovesicle (lipoTEL). Both nano-formulations showed spherical morphology and sustained release of TEL. In vitro, nanoTEL restored oxidative equilibrium, attenuated reactive oxygen species levels, enhanced the uptake of glucose analogue, and increased the expression of glucose transporter protein 4 better than lipoTEL. In a streptozotocin-induced murine model of diabetes, nanoTEL lowered blood glucose levels, improved glucose tolerance, and promoted insulin synthesis and secretion significantly better than lipoTEL. Moreover, nanoTEL was found superior in ameliorating the pancreatic inflammatory microenvironment by regulating NF-κBp65, HIF-1α, and PPAR-γ expression; modulating IL-1β, IL-6, tumor necrosis factor-α, IL-10, and IL-4 levels and inducing the polarization of macrophage from M1 to M2. Further, nanoTEL administration induced angiogenesis and promoted the proliferation of pancreatic cells to restore the structural integrity of the islets of Langerhans more efficiently than lipoTEL. These findings collectively suggest that nanoTEL outperforms lipoTEL in restoring the function of pancreatic β-cells by modulating the pancreatic inflammatory microenvironment and show potential for the treatment of DM.

SIMULTANEOUS ESTIMATION OF THREE ANTIHYPERTENSIVE AGENTS BY ABSORBANCE CORRECTION METHOD

The estimation of amlodipine besylate (AML), telmisartan (TEL) and chlorthalidone (CHL) in a tablet form has been carried out simultaneously using a straightforward, precise, accurate UV method using absorbance correction. This procedure involved the measuring of absorbance at three wavelengths using methanol as a solvent. The wavelengths selected were 364.6 nm absorbance due to amlodipine besylate only, 322 nm absorbance due to telmisartan and amlodipine besylate and 275 nm absorbance due to all three drugs. The plot of absorbance versus concentration was found to be linear in concentrations ranging from 2-18 µg mL-1 for AML, 10-60 µg mL-1 for TEL and 2-20 µg mL-1 for CHL. The different parameters of the method were validated as per the requirements given by ICH. The results were validated statistically and % RSD for proposed method were ≤2. The above suggested approach can be used for simultaneously estimating the above medications in a combined dosage form.