Bosentan

Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. The aim of the present study was to develop sustained release formulation of Bosentan to maintain constant therapeutic levels of the drug for over 12 hrs. Various synthetic polymers were employed as polymers. Bosentan dose was fixed as 62.5 mg. Total weight of the tablet was considered as 200 mg. the tablets are prepared by employing direct compression method using 8mm punch. And the Polymers were used in the concentration of 31.5, 41.25, 62.5 mg concentration. All the formulations were passed various physicochemical evaluation parameters and they were found to be within limits. And the drug and excipient compatibility studies showed that there is no interaction between the drug and polymers employed in the formulation. Whereas from the dissolution studies it was evident that the formulation F3, F16 showed better and desired drug release pattern i.e., 98.15±0.06, 96.64±0.02 % respectively in 12 hours. the project work is successful in developing sustained release formulations of Bosentan.

A simple, sensitive and accurate method employing HPTLC has been developed and validated as per ICH guidelines for determination of Bosentan in bulk and Tablet dosage form. The absorption maxima of the drug were found to be 288 nm in methanol. The method was validated as per ICH guidelines. The linearity range was found to be 50-300 ng/ml with a regression coefficient of 0.98.Subsequent validation parameters like precision, repeatability in terms of Interday and Intraday precision and recovery studies were evaluated with satisfactory results, the % RSD for these parameters was found to be 1.73%,1.30-0.48%,1.80 – 0.45 % , 1.54 – 1.48 % respectively with an Rf value of 0.23.

An accurate and precise high performance liquid chromatographic method was developed for quantitative estimation of bosentan in tablet dosage forms. Chromatographic separation of the drug was achieved on a Kromasil C18 column (150 x 4.6 mm; 5µ) by eluting with a mobile phase consisting of phosphate buffer (pH 4.0) and acetonitrile (30:70 v/v) at a flow rate of 1.0 mL/min. The drug in the eluate was monitored by U V detection at 270 nm. The retention time obtained for the drug was 3.54 min. The calibration curve plotted was linear over the range of 25-175 µg/mL of the drug. The validation of the method was done following the ICH guidelines. The proposed method could be applied for determination of bosentan in its tablet dosage forms without any interference from excipients. The method is suitable for routine quality control analysis of bosentan formulations.

This study is aimed at Developing and validating an UPLC method for Bosentan and its related substances that might coexist in bulk drugs and its tablet formulations as impurities that may originate from synthesis process or degradation. A chromatographic system consisting Waters Acquity UPLC HSS PFP, 2.1x 50mm (2.5 µm) column, mobile phase of 0.02M KH2PO4with pH 2.0 as Buffer phase and Acetonitrile: Methanol in 1:1 ratio as organic phase, with gradient elution at flow of 0.6 mL/min and UV detector set at 220 nm has shown a good chromatographic separation for Bosentan and its related substances. The developed method was validated as per ICH Guidelines and shown equivalency with API Vendor method. The developed UPLC method has run time of only 13 minutes making the method productive and may be applied for Quality control Testing.

  Bosentan is a dual endothelin receptor antagonist. It is used in the treatment of pulmonary artery hypertension (PAH). Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors [endothelin type-A (ETA) and/or type-B (ETB)] on the surface of endothelial and smooth muscle cells. Bosentan is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer. Bosentan, is a non-peptide and orally active. Bosentan is highly protein-bound, with approximately 98% bound to albumin. This paper reviews the pharmacological and pharmaceutical properties of Bosentan. Bosentan could be an attractive target for the generic industries.