Dissolution Of Telmisartan Research Articles

Prediction of Chemistry of Cocrystallization and its Realistic Impact on the Enhancement of Solubility and Dissolution of Telmisartan: Molecular mechanics, ab initio and Descriptor Analysis

Prediction of Chemistry of Cocrystallization and its Realistic Impact on the Enhancement of Solubility and Dissolution of Telmisartan: Molecular mechanics, ab initio and Descriptor Analysis

Preparation and Evaluation of Telmisartan Solid Dispersion as Sublingual Tablets

Background: Telmisartan is an antihypertensive angiotensin II receptor antagonist drug commonly used to treat hypertension and renal disease. Based on the Biopharmaceutical Classification System. It’s a Class II poorly soluble drug. Objective: To prepare a sublingual tablet by increasing the dissolution and solubility of Telmisartan utilizing the solid dispersion method. Methods: Three methods were obtained to prepare the solid dispersion of telmisartan: solvent evaporation, Kneading, and microwave method. Each method uses surplus as a hydrophilic carrier in different ratios of 1%, 2%, and 3%. Preparation of ternary solid dispersion by adding potassium carbonate salt to the binary solid dispersion. After that preparing the sublingual tablets by applying a direct compression method, using different types and ratios of superdisintegrants such as crospovidone, croscarmellose and sodium starch glycolate in 5% and 10%. Study the evaluation tests of sublingual tablets, such as friability, hardness, disintegration time and dissolution time. Results: The solid dispersion showed an improvement in solubility over the pure medication. The best result was obtained with the formula (Telmisartan, soluplus and k2co3 salt at 1:1:0.3 ratio) prepared by microwave method, in this method and the high ratio of soluplus, the solubility increased more than the solvent evaporation and kneading method. The selected tablet is prepared using crospovidone 10% as a superdisintegrant that appears disintegration time in 5 seconds and releases in 1 min in dissolution media. Conclusion: The solubility and dissolution of Telmisartan were improved by microwave-based ternary solid dispersion using hydrophilic carriers and salt in a ratio of 1:1:0.3 (drug: carrier: salt). The analysis exerts the increases in wettability, enhanced solubility, and dissolution due to conversion from crystal to amorphous state. Received May. 2023 Accepted Aug. 2023 Published Jan. 2024

Improvement of Solubility and Dissolution of Telmisartan by Solid Dispersion Technique: An investigation on Effects of Carrier using Multiple Comparison Analysis

Improvement of Solubility and Dissolution of Telmisartan by Solid Dispersion Technique: An investigation on Effects of Carrier using Multiple Comparison Analysis

In Vitro Sensitivity Analysis of the Gastrointestinal Dissolution Profile of Weakly Basic Drugs in the Stomach-to-Intestine Fluid Changing System: Explanation for Variable Plasma Exposure after Oral Administration.

An in vitro methodology for simulating the change in the pH and composition of gastrointestinal fluid associated with the transition of orally administered drugs from the stomach to the small intestine was developed (the stomach-to-intestine fluid changing system (the SIFC system)). This system was applied to in vitro sensitivity analysis on the dissolution of weakly basic drugs, and the obtained results were discussed in relation to the intrasubject variability in the plasma exposure in human bioequivalence (BE) study. Three types of protocols were employed (steep pH change: pH 1.6 FaSSGF → pH 6.5 FaSSIF, gradual pH change: pH 1.6 FaSSGF → pH 6.5 FaSSIF, and high gastric pH: pH 4.0 FaSSGF → pH 6.5 FaSSIF). Regardless of the protocols and the forms of drug applied in active pharmaceutical ingredient powder or formulation, dissolution profiles of pioglitazone after fluid shift were similar and the final concentrations in FaSSIF were approximately equal to the saturation solubility in FaSSIF, supporting its small intrasubject variance in human BE study. In contrast, dissolved concentration of terbinafine in the SIFC system became less than half in the high gastric pH protocol than that in other protocols, suggesting the fluctuation of gastric pH as one of the factors of high intrasubject variance of terbinafine in human. Plasma exposure of telmisartan was highly variable especially at the high dose. Although the dissolution of telmisartan in the SIFC system was greatly improved by formulation, it considerably fluctuated during fluid shift especially at the high dose, which corresponds well to in vivo results.

Improved in vitro and in vivo properties of telmisartan in the co-amorphous system with hydrochlorothiazide: A potential drug-drug interaction mechanism prediction

The aim of this study is to improve in vitro and in vivo properties of an antihypertensive poorly soluble drug Telmisartan (TEL) by co-amorphization with a pharmacologically relevant drug Hydrochlorothiazide (HCT), and to improve the stability of single amorphous drugs. Herein, TEL-HCT co-amorphous systems (CAMs) (1:1, 2:3, 1:2, 1:3) were prepared by solvent evaporation. The apparent solubility and the dissolution of TEL in the TEL-HCT CAM (1:3) were increased by 79 times and 10 times compared to crystalline TEL, which showed the optimal properties. Cmax and AUC0-48h value of TEL-HCT CAM (1:3) were 10-fold and 3-fold as the crystalline state. Moreover, TEL-HCT CAM (1:3) remained stable in 60 °C, 0 % RH (30 days), 40 °C, 75 % RH (90 days) and 25 °C, 0 % RH (180 days). Positive ΔTgs were observed in all CAMs, suggesting the existence of potential intermolecular force. Fourier Transform-Infrared and Raman spectra were used to further prove the drug-drug interaction and predict potential mechanisms. Therefore, in the strategy of combined medication, CAM provides a promising way to transfer drugs with poor properties into systems with enhanced dissolution, greater bioavailability, and stabilized amorphous state, which has been proven in this study.

Assessment of Effects of Solvents on Cocrystallization by Computational Simulation Approach.

The sole purpose of this study is to improve the solubility and dissolution of telmisartan by cocrystallization technique and apply a computational simulation approach to assess the nature of chemical interactions between telmisartan and coformer as well as the solvent contribution to the molecules for furnishing cocrystallization. The effects of various concentrations of coformer i.e. oxalic acid on physicochemical parameters and drug release were investigated. Solubility studies suggested that cocrystallization technique with oxalic acid helps to increase the solubility of pure telmisartan of about 7 folds and drug release study revealed that telmisartan-oxalic acid cocrystals showed greater dissolution as compared to pure telmisartan. SEM study suggested that prepared telmisartan cocrystals showed rhomboid-shaped crystals with sharp edges and smooth surface. FTIR study revealed that shifting in the vibrational frequencies of C=O group of telmisartan in telmisartan- oxalic acid cocrystal indicates the formation of supra molecular hetero synthon of the cocrystal. DSC and XRD studies confirmed the formation of telmisartan-oxalic acid cocrystals. Computational simulation approach revealed that telmisartan and oxalic acid can interact with each other in the presence of methanol and water where oxalic acid can form interactions principally with the others. The interactions, thereof, may form several associations or bondings in between the drug and carrier modifying the planarity, bond energy, bond angles of both which subsequently lead to cocrystallization. So, the present research concluded that prepared telmisartan-oxalic acid cocrystal is a successful application of crystal engineering approach to improve the physicochemical properties as well as to enhance the solubility and dissolution of telmisartan.

Solubility and modeling of telmisartan in binary solvent mixtures of dichloromethane and (methanol, ethanol, n-propanol, or n-butanol) and its application to the preparation of nanoparticles using the supercritical antisolvent technique

In this study, the mole-fraction solubility data for telmisartan in dichloromethane + primary alcohol (methanol, ethanol, n-propanol or n-butanol) mixtures were measured at five different temperatures by employing a solid-liquid equilibrium using the shake-flask technique. In addition, the melting temperature and enthalpy of telmisartan were determined by differential scanning calorimetry, while powder X-ray diffraction analysis was used to evaluate the crystal form of telmisartan obtained before and after the solubility experiments. The solid state characterization confirmed no transformation of telmisartan into polymorphs. The solvent synergistic effect was observed in all binary mixtures. In particular, the telmisartan solubility in the mass fraction values of dichloromethane (w) of 0.8 at 298.15 K was found to be approximately 90.77 and 4.98 times higher than that in pure methanol and pure dichloromethane, respectively. The experimental solubility data for telmisartan were correlated and fitted to the van't Hoff, modified Apelblat, simplified CNIBS/R-K, Jouyban-Acree, Jouyban-Acree-van't Hoff, Jouyban-Acree-Apelblat, Ma, and Sun models. The thermodynamic parameters, such as the dissolution enthalpy (∆H°), Gibbs free energy (∆G°), and dissolution entropy (∆S°), confirmed that the dissolution of telmisartan in the mixtures was an endothermic process. Furthermore, dichloromethane and primary alcohol mixtures (w = 0.8) were used as the solvent in the preparation of telmisartan nanoparticles using the supercritical antisolvent (SAS) technique. The smallest particle size (630.8 nm) of the telmisartan nanoparticle obtained from a solvent mixture of dichloromethane and methanol was obtained. Results confirmed that the solubility data and estimated equations for telmisartan in the dichloromethane + primary alcohol mixtures with a strong synergistic solvation are useful in research and development for the purification and preparation of nanoparticles as well as in future studies on telmisartan to design and develop dosage forms.

The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations

In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%. Changing the salt forming agent as well resulted in approximately 20% of flux reduction compared to the brand formulation. This significant difference was clearly shown in the published in vivo results as well. The use of additional lactose monohydrate in the formulation also leads to approximately 10% reduction in flux. The results show that by changing excipients, the dissolution of telmisartan was not altered significantly, but the flux through the membrane was found to be significantly changed.These results pointed out the limitations of traditional USP dissolution tests and emphasized the importance of simultaneously measuring dissolution and absorption, which allows the complex effect of formulation excipients on both processes to be measured. Moreover, the in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo bioequivalence study results.

Determination of Effect of pH, Temperature and RPM on dissolution of Telmisartan by Two Factorial Design

The main intend of present study was to determine how the dissolution parameters such as rpm, temperature and pH affects drug release for the marketed Telmisartan IR tablets. They were quantitatively and statistically studied by applying two factorial design. The dissolution parameters like temperature of the medium, pH of the medium and rpm were taken from low level to high levels and factorial design was applied at -1,+1 levels. The experiment was performed and drug release was estimated. Factorial design proved, the drug release up to 90% within 30 min. Finally, change in pH was found to be having more prominent effect on drug release than temperature and rpm.

Dissolution rate improvement of telmisartan through modified MCC pellets using 32 full factorial design

Context: Microcrystalline cellulose (MCC) is the most widely used excipient for the production of pellets but it retards the release of poorly water soluble drugs. Objective: The present investigation reports incorporation of camphor, cross carmellose sodium (CCS) and spray dried lactose (SDL) into MCC pellets to enhance the dissolution rate of telmisartan. Materials and methods: A full factorial design (32) was used in the study. Concentration of camphor and CCS was selected as independent variables whereas percentage porosity and percentage drug release at 60min were selected as dependent variables. Pellets were produced by extrusion–spheronization technique and evaluated for percentage yield, particle size analysis, flow characteristics, percentage porosity, drug content and in vitro drug release. Contour plots and 3-D surface plots were presented for graphical expression of the results. Results and discussion: Pellet formulations exhibited acceptable morphological, flow and mechanical properties. As against to 38.54% drug release after 60min with MCC pellets, pellets prepared with optimized formulation, composed of proper combination of MCC, SDL, camphor and CCS, released 100% drug after 60min. Conclusion: Our study underlines the fact that dissolution of telmisartan from MCC pellets can be successfully enhanced by incorporating water soluble excipient, disintegrant and pore formers.

Preparation and Characterisation of Telmisartan Solid Dispersions Prepared by Solvent Evaporation Method

Enhancement of the solubility and dissolution of Telmisartan using solid dispersion (SD) with PVP K-90, PVP K-30 and Eudragit RS-100 by a solvent evaporation technique. In this method, SDs were prepared by the solvent evaporation method using minimum quantity of ethanol. Infrared (IR) spectroscopy was performed to identify physio-chemical interaction between the drug and the polymers, and differential scanning calorimetry (DSC) was performed to identify the melting point of SDs and their effect on dissolution behaviour. Morphology of the SDs was studied using scanning electron microscopy (SEM) and powdered X-ray diffractometry (PXRD). A comparative evaluation of the dissolution of Telmisartan SDs, pure drug and marketed formulation (tablet) was carried out. In the Results section, dissolution of Telmisartan significantly improved in SDs as compared to the pure drug. Telmisartan exhibited better aqueous solubility in the presence of all the polymers used. IR spectroscopy and DSC showed no change in the crystal structure of Telmisartan. It was concluded that SD prepared by the solvent evaporation method can be successfully used for the improvement of dissolution of Telmisartan.

FORMULATION AND OPTIMIZATION OF TELMISARTAN MULTIPARTICULATE SYSTEM USING A 22 FACTORIAL DESIGN

Telmisartan is used in the treatment of hypertension. It exhibits poor water solubility. It belongs to class II of Biopharmaceutical Classification system (BCS). It needs enhancement in dissolution and hence bioavailability. The dissolution of drug was improved by coating the drug and carrier over sugar spheres.Size of sugar spheres and concentration of the carrier were two critical variables that were found to affect the dissolution of drug. A 22 factorial design was used to study the effect of concentration of carrier and size of the non-pareil seeds on dissolution. Dissolution of telmisartan was found to increase with increasing concentration of carrier and decreased with respect to size of non-pareil seeds.