Olmesartan

The stability of drug product or a drug substance is a critical parameter which may affect purity, potency and safety. The stability indicating method is that employed for the analysis of stability samples in pharmaceutical industry. Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated condition. Thus, this review discuss the current trends in performance of stability indicating method to force degradation by providing strategy for conducting studies on degradation mechanism Stability testing by reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been performed of cilinidipine and olmesartan. All the drugs were separated. The retention time of cilinidipine and olmesartan was founded respectively. Ranges of 50 -300μg/ml for cilinidipine and 25 – 150 μg/ml for Olmesartan. Keyword: Olmesartan, Cilnidipine, RP-HPLC.

Current study was undertaken to improve solubility and bioavailability of poorly water soluble drug, Olmesartan. A mixed hydrotropic method was used to prepare the hydrotropes of Olmesartan. On the basis of screening Sodium Benzoate, Potassium Acetate and Tri Sodium Citrate hydrotropes were selected to prepare various hydrotropic solid dispersions of Olmesartan using selected hydrotropic agent in different ratio with the drug. The prepared solid dispersions were evaluated for solubility analysis, Drug Content Estimation, Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and In-vitro Dissolution Study of hydrotropes. From the study the results revealed that solubility was increased by using certain ratio (1:1:1:0.5) of drug with hydrotropic agents alone as well as in the combination. In the present study an attempt was made to prepare hydrotropes of a poorly water soluble drug Olmesartan to enhance the solubility and bioavailability of drug. The screening of different hydrotropic agents was performed to evaluate the best suited agent for drug hydrotrophs. On the basis of solubility analysis, the Sodium Benzoate, Potassium Acetate and Tri Sodium Citrate agents   have the ability to enhance the solubility of the drug more than 3 times of its original solubility. The method is economical and simple, to enhance the solubility of Olmesartan.

The present study involved preparation of solid dispersions of Olmesartan medoxomil to improve the aqueous solubility and dissolution rate in order to enhance bioavailability. Olmesartan is a BCS Class II anti-hypertensive drug, having low aqueous solubility and low bioavailability of 26%.  In the present study, solid dispersions of Olmesartan with different carriers like Poloxamer 407, PEG 4000  and crospovidone in different ratios (1 : 1, 1 : 2, 1 : 3, 1 : 4) were prepared by solvent evaporation method.  The formulations were further characterized for percentage yield, drug content, in vitro release study,  and stability study. In vitro release studies revealed that the solid dispersions prepared by solvent evaporation method crospovidone (1 : 4) was considered as the best formulation because of its faster drug release among all formulations.  Infrared spectroscopy (IR) studies revealed that no interactions exist between drug and polymer. Powder X-ray diffraction studies showed a significant decrease in crystalline nature of drug in solid dispersions. In conclusion, solid dispersions of Olmesartan in crospovidone (1:4) have shown to be a promising approach to enhance the bioavailability of Olmesartan.

A specific, sensitive and rapid LCMS/MS method was developed for simultaneous determination of olmesartan and hydrochlorothiazide in human plasma using olmesartan D4 and hydrochlorothiazide 13C6 as internal standards. Solid-phase extraction (SPE) method was used to extract the analytes from biological matrix. Analysis was carried out on phenomenex Luna C18 column with a flow rate of 0.600 mL/minute with 80% flow splitting. Detection was carried out on a triple quadrupole linear mass spectrometer, equipped with turbo ion spray source. The method was validated over the concentration range of 32.32 ng/mL to 2676.60 ng/mL for olmesartan and 5.12ng/mL to 423.83ng/mL for hydrochlorothiazide. Olmesartan and hydrochlorothiazide were found to be stable upto 75 days in K3EDTA based Human Plasma at -20ºC. Inter and intra-batch precision of olmesartan and hydrochlorothiazide were less than 15% and the accuracy was within 85–115% in plasma.  The mean % recovery was 53.09 % for olmesartan and 59.12 % for hydrochlorothiazide in human plasma. The stability of olmesartan and hydrochlorothiazide in plasma were confirmed up to five freeze-thaw cycles at -20°C and on bench up to 24 hours and 15 minutes at ambient temperature. The method was validated satisfactorily and was suitable for the quantitation of olmesartan and hydrochlorothiazide from plasma samples in a pharmacokinetic study.

A new stability indicating RP-HPLC method was described for the assay of olmesartan in market formulations. This developed RP-HPLC method was based on high performance liquid chromatographic (HPLC) separation of olmesartan with the use of a reversed phase HPLC column [Kromasil BDS, C18, 100 x 4.6 mm, 5μ] with mobile phase consisting of .01M KH2PO4 buffer (pH-4.5) and acetonitrile in the ratio of 55:45 %v/v at ambient temperature. The flow rate of the mobile phase was adjusted to 1.0mL/min and the injection volume was 10μL. Detection was performed by photodiode array detector at a wavelength of 257nm and the chromatographic runtime was 8 minutes for the analysis. The reliability and analytical performance of the proposed method, including linearity, range, precision, accuracy, detection and quantitation limits, were statistically validated. The proposed method can be adopted apparently for routine quality control analysis of raw materials, formulations and testing

An accurate, efficient Stability indicating reversed-phase high-perfomance liquid chromatographic (RP-HPLC) method has been developed and validated for the simultaneous estimation of Olmesartan, Cilnidipine and Chlorthalidone. All the drugs were separated on a KROMASIL 250 x 4.6 mm, column packed with 5 µm particles. The mobile phase, optimized through an experimental design, was a 45:55 (v/v) mixture of acetonitrile and Ortho phosphoric acid buffer(0.1%OPA), pumped at a flow rate of 1 ml/min. UV detection was performed at 230 nm. The retention time of Olmesartan, Cilnidipine and Chlorthalidone was found to be 2.280min, 8.356 min and 2.804min respectively. The method was validated in the sample concentration ranges of 20-120 µg/ml for Olmesartan and 5-30 µg/ml for Cilnidipine, and Chlorthalidone 6.25-37.5µg/ml.  The method demonstrated to be robust, resisting to small deliberate changes in pH and flow rate of the mobile phase. The LOD values were 0.08µg/ml, 0.04µg/ml and 0.05 µg/ml, while the LOQ values were 0.24µg/ml, 0.12µg/ml and 0.16µg/ml for Olmesartan, Cilnidipine and Chlorthalidone respectively.

A new simple fast accurate and economical reverse phase high performance liquid chromatographic method was developed for the determination of Ramipril and Olmesartan in bulk and tablet dosage form. The separation was eluted on a Inertsil C8 column (100 mm x 4.6 mm; 5µ) using a mobile phase mixture of mixed phosphate buffer 6.8 and acetonitrile in a ratio of 65:35 v/v at a flow rate of 1.0ml/min. The detection was made at 219 nm. The retention times were 2.28min for Ramipril and 3.76min for Olmesartan. Calibration curve was linear over the concentration range of 2.5-15 µg/ml for Ramipril and 10 to 60 µg/ml for Olmesartan. The propose method was validated as per the ICH guidelines parameters like Linearity, specificity, precision, accuracy, robustness and ruggedness. The method was accurate, precise, specific and rapid found to be suitable for the quantitative analysis of the drug and dosage form.