Telmisartan

Telmisartan is a long-acting angiotensin II receptor blocker widely used for hypertension management. Although generally well tolerated, it has been associated with various adverse drug reactions (ADRs) ranging from mild symptoms to serious events. To review telmisartan’s ADR profile from a clinical pharmacist’s perspective and illustrate key insights through a case of drug-induced acute kidney injury (AKI). A comprehensive literature review and analysis of the Pharmacovigilance Programme of India data were conducted. A 40-year-old male who developed pre-renal AKI following dose escalation of telmisartan is presented. Common ADRs include dizziness, headache, diarrhoea, and respiratory symptoms. Serious reactions encompass hyperkalemia, angioedema, hypotension, and AKI. PvPI reports have highlighted rare cutaneous reactions such as lichenoid keratosis. In the case study, serum creatinine rise from 1.3 to 1.8 mg/dL within 48 hours of increasing the telmisartan dose and normalized after discontinuation. Vigilant monitoring and pharmacist-led interventions are essential to detect and manage telmisartan-related ADRs, optimize therapy, and ensure patient safety.

Hypertension (HT) is a very common disorder, particularly for past middle age. It is not a disease in itself, but is an important risk factor for cardiovascular mortality and morbidity. For improved treatment of hypertension, Telmisartan and Benidipine HCl is the newer combination in market, this combination was developed to improve medication for Stage II hypertension. The aim of this review is to focus on comprehensive update of different analytical methods used for estimation of anti-hypertensive drugs like Telmisartan and Benidipine HCl for the treatment of hypertension. This review delivers a detail description on different analytical methods like UV and RP-HPLC for Telmisartan and Benidipine HCl individually and combination with other drugs. For this review, data searches were conducted by scientific papers in the literature as well as in official compendium. All reported methods are found to be simple, accurate, economic, precise and reproducible in nature.

A sensitive and rapid HPLC method was developed and validated for the determination of potential genotoxic impurities i.e (Bromomethyl)biphenyl methyl ester and (Dibromomethyl)biphenyl methylester at trace level in Telmisartan drug substance by applying the concept of threshold of toxicological concern (TTC). The HPLC method was developed and optimized on Symmetry Shield RP18, 3.5 m (150mm × 4.6mm) column with oven temperature maintaining at 40°C and 0.02M Phosphate buffer pH 2.5 was chosen as mobile phase A and mixture of acetonitrile and Phosphate buffer (55:45) was selected as mobile phase B in gradient reverse phase mode in isocratic mode of composition. Chromatographic parameters i.e flow rate: 1.0 ml/min, wavelength detection: 205 nm, injection volume: 20µl and run time: 25 min were applied in this methodology.  Based on validation data, the method is found to be specific, sensitive, accurate and precise. The established limits of Limit of detection and Limit of quantification for subjected impurities are found to be 2.4 µg/g and 4.7 µg/g respectively for each impurity. The recovery at LOQ level obtained was 98.2% for (Bromomethyl) biphenyl methyl ester and 99.2% for (Dibromomethyl) biphenyl methyl ester. This method can be used as good quality control tool for quantization of these impurities at low level. The experimental results are discussed in detail in this research paper.

A new selective, sensitive and Rapid Reverse phase-UPLC method was developed and validated to determine the known potential impurities present in Telmisartan (TL) and Hydrochlorothiazide (HC) in fixed dose combination drug product. The quantification was carried out by using Acquity UPLC, HSS T3 (100 × 2.1) mm, 1.8m column, with a flow rate of  0.5mL/min at 225 nm .The mobile phase consists of 0.1% ortho phosphoric acid pH adjusted to 2.6 with diluted sodium hydroxide as Mobile phase A and acetonitrile as Mobile phase B. Separation of the impurities was achieved within 10.0 minutes of run time. Typical retention times of TL and HC were found to be about 5.4 and 2.0 minutes respectively. The product was subjected to various degradation conditions and validated in terms of linearity, precision, accuracy, LOD, LOQ and robustness in accordance with ICH guidelines. The known impurities quantified in this study were HC imp-1 to 4 for Hydrochlorothiazide and TL imp-1 to 6 for Telmisartan. Recovery was established for all the impurities with respective to LOQ to 150%. The data supports that the newly developed method is capable to determine all the potential impurities of TL and HC.

The aim of present work was to develop an accurate, precise, reproducible and economical UV spectrophotometric method for estimation of 1H, 1’-H-2, 2’-Bibenzimidazole Impurity In Telmisartan Bulk and Formulation. This method was based on area under curve of UV spectrum between 235 to 254 nm and validated as per ICH guideline Q2 (R1). The method has followed linearity in the range of 5-30μg/ml. The value of correlation coefficient was 0.998. Satisfactory values of Percent relative standard deviation for the intra-day and inter-day precision indicated that method is precise. Results of the recovery studies (97.63% to 98.66 %) showed accuracy of the method. LOD and LOQ were calculated as 0.3221μg/ml and 0.9761 μg/ml, respectively. The developed method can be used for routine estimation of 1H, 1’-H-2, 2’-Bibenzimidazole Impurity In Telmisartan Bulk and Formulation.

The objective of the present study was to enhance the dissolution profile, absorption efficiency of water insoluble drugs like Telmisartan. A novel “Powder Solution Technology” involves absorption and adsorption efficiency, which makes use of liquid medications admixed with suitable carriers and coating materials and formulated into a free flowing, dry looking, non adherent and compressible powder forms. Based upon a new mathematical model expression improved flow characteristics and hardness of the formulation has been achieved by changing the proportion of carrier and coating material ratio from 15:1 to 5:1. Avicel ® PH 102 was showing acceptable flow properties compared with Avicel ®PH 200. Higher dissolution rates were observed in optimized liquisolid formulation containing Poly ethylene glycol 400 and Avicel ®PH 102 compared with marketed product (SARTAN® 20mg tablets). Poly ethylene glycol 400 was showing highest solubility compared with poly ethylene glycol 200, propylene glycol and glycerin.The crystalline state of telmisartan drug state was changed to amorphous state due to liquisolid formation and was confirmed by both X-ray diffraction and Fourier transform infrared spectroscopy results, this transition occur as the drug is in solution form. Additionally, increasing the wetting properties and subsequent surface area of the drug available for dissolution.

Present study was carried out to study compatibility of Atorvstatin Calcium (ATR) and Telmisartan (TEL) with selected generally regarded as safe (GRAS) excipients and to prepare bilayer tablet. Isothermal stress testing was performed in binary mixtures which was subjected to 50°C for 4 weeks. Isothermal stressed samples were evaluated with RP-HPLC method and FTIR analysis. A trial was conducted with single disintegrant and diluent with direct compression technique and in-vitro dissolution was carried out. To improve the release profile of ATR layer, multiple disintegrants were used namely croscarmellose sodium (CCS), sodium starch glycolate (SSG)  and crosprovidone (CP). These disintegrants were taken as variable in Box-behnken design (BBD) in Minitab 16.2.3.0. The tablets were prepared from obtained design formulations by direct compression. Similarly, Telmisartan layer was prepared by wet granulation technique. TEL was treated with alkalizing agent, sodium hydroxide in stoichiometrical proportion. Croscarmellose sodium, sodium starch glycolate and crosprovidone were taken as variable and subjected to BBD. Intra and extra granulation was done with mixtures of disintegrants. Optimized formulation as per response surface optimizer in Minitab 16 contains be 10.0 mg of SSG, 7.36 mg of CP and 10.0 mg of CCS per tablet for ATR layer. Similarly in case of TEL tablet, it was found that as concentration of SSG, CP and CCS increases, the release of drug also increases. When multiple disintegrants were used in the combination, better release was obtained. Optimize formulation as per response surface optimizer in Minitab 16  contains 22.03 mg of SSG, 15 mg of CP and 15 mg of CCS per tablet for Telmisartan layer. Bilayer tablet was prepared with this optimized formulation in 10 station compression machine. The prepared bilayer tablet was further evaluated and in-vitro dissolution were compared with market products. Thus, the conversion of salt form, optimized combination of disintegrants, use of polyvinyl pyrrolidone K-30 as carrier, intra and extra granulation was observed to be effective in release of TEL from the dosage form where as only the optimized combination of disintegrants was  sufficient for release of ATR from the dosage form.

Two simple, specific, precise and accurate spectrophotometric methods have been developed for the simultaneous estimation of Telmisartan (TEL) and Amlodipine besylate (AML) involving: second derivative Spectrophotometric method (I) and first derivative Ratio -Spectrophotometric Method (II). Method (I) is based on measurement of amplitude of second derivative spectrum absorbance at two wavelengths; 329 nm and 368 nm for Telmisartan and Amlodipine besylate respectively. The latter (method II) depends on measurement of amplitude of the first derivative of the ratio spectrum at two wavelengths, 319 nm and 288 nm for Telmisartan by using 2 µg/mL of AML as a divisor and 393 nm for Amlodipine besylate by using 4 µg/mL of TEL as a divisor. Beer's law obeyed in concentration range of 1 - 35 µg/ mL and 2- 16 µg/ mL for Telmisartan and Amlodipine besylate respectively for both methods. The proposed methods are recommended for routine analysis since they are rapid, simple and specific. The described UV methods were successfully employed for the analysis of each drug in their combined dosage form. For method (I), the mean% recoveries were found to be 100.49±0.15 for Amlodipine besylate and 98.99±1.83 for Telmisartan. For method (II), the mean% recoveries were found to be 99.55±0.92 and 100.48±1.69 for Telmisartan at 319 nm and 288 nm respectively and 99.92±1.69 for Amlodipine besylate at 393 nm. The validation of methods was carried out utilizing ICH guidelines.

A simple, accurate, precise and stability-indicating RP-HPLC method has been developed and validated for the simultaneous estimation of Telmisartan and Chlorthalidone in fixed-dosage formulation. The separation was achieved on a octadecyl C-18 reversed phase column (Symmetry C-18, 250mm x 4.6mm , 5µ) using acetonitrile:phosphate buffer at pH 6.5 (70:30 v/v) as mobile phase at a flow rate of 1.0mL/min and temperature of 25°C. The UV detection was carried out at 270nm. The retention time of Chlorthalidone and Telmisartan was found to be 5.48 and 13.38 min. respectively. The method has been validated for Specificity, Linearity, Accuracy, Precision and Robustness. The calibration curve for Chlorthalidone and Telmisartan were linear from the range of 1.25-20.01 µg/mL and 8.0 to 128.4 µg/mL respectively. The mean recoveries obtained for Telmisartan and Chlorthalidone were 100.9% and 99.7% respectively. The developed method was found to be Specific, accurate, Precise, Robust and rapid for the simultaneous estimation of Telmisartan and Chlorthalidone in Telmisartan and Chlorthalidone Tablets 80mg/12.5mg.

The emerging new fixed dose combination of Glipizide (GLZ) as sustained release and Telmisartan (TEL) as immediate release were formulated as a bilayer matrix tablet using guggul. Guggul used as a binding agent with three different concentrations (70%, 80%, and 90%; F1-F6) was used for the preparation of first layer of tablet containing glipizide. The conventional tablet of telmisartan was prepared as a second layer. Prepared bilayer tablets were studied for the in vitro release study carried out at pH 1.2 for first two hours and then at pH 6.8 for 6 hours using USP dissolution apparatus II (Basket). All the evaluation tests were found to be within the acceptance limits specified in Indian Pharmacopeia. The assay and dissolution study of tablets were done by HPLC which was developed and validated according to the ICH Q2 (B) guidelines. The contents of assay of the tablets were found to be 90.92% - 103.84% for F2-F5. The release of glipizide from the tablet was extended up to 8 h. Tablet containing 2.5 mg of glipizide with 80% of guggul release of drug after 8 h was found to be 82.36% and tablet containing 5 mg of glipizide with 90% guggul release of glipizide after 8 h was found to be 74.67%. The release pattern of each formulation (F2-F5) was fitted into the dissolution kinetics models and all the formulations were best fitted in the Higuchi model kinetic. From the results, we have concluded that the guggul act as a binding agent as well as rate retarding agent.