Tablet Formulation Studies on Recrystallized Active Pharmaceutical Ingredients of Valsartan and Olmesartan Medoxomil

Both the Valsartan (VAL) and Olmesartan medoxomil (OLM) are widely prescribed anti-hypertensive agents with angiotensin II type I receptor antagonistic activity. Both VAL and OLM are type of BCS class II drugs and having a low and variable oral bioavailability. Recrystallization of VAL and OLM from different organic solvents improved its aqueous solubility and thereby in vitro dissolution properties. In the present investigation, tablets containing Valsartan (VAL), Olmesartan medoxomil (OLM and) recrystallized products were prepared by direct compression method and evaluated for drug content, uniformity of weight, hardness, friability, disintegration time and dissolution properties. All the tablets fulfilled the compendial requirements with regarding to weight variation, friability and disintegration time etc for immediate release tablets. The DP15 (drug percent dissolved at 15 min) values for V-1 (tablets of VAL), V-4 (tablets of methanol recrystallized product with crospovidone as disintegrant) and DIOVAN™ 40mg tablet formulations are 45.97, 98.95 and 82.65 respectively and V-4 formulation showed higher dissolution rate when compared to other formulations. The DP15 values of O-1(tablets of OLM), O-4 (tablets of acetonitrile recrystallized product with crospovidone as disintegrant and OLMY™ (20mg) tablet formulations are 29.25, 99.93 and 84.82 respectively. O-4 tablet formulations showed higher dissolution rate when compared to other tablet formulations. Keywords: Valsartan, Olmesartan medoxomil, Recrystallization, Aqueous solubility

In silico assessment of chronic toxicity of a combination drug namely ‘Olmesartan medoxomil and Hydrochlorothiazide’, marketed in Bangladesh

Background Nowadays combination therapy has become more popular due to their additional effect, synergistic effect and antagonistic effect. Any of these can influence the treatment profile. Combination therapy is used to treat some chronic diseases like diabetes, hypertension, cancer etc. But recently India has banned some fixed dose drug combinations due to their increased chances of adverse drug effects and drug interactions. So it is the time to take a look on the present drug combinations available in Bangladesh. An in silico study may provide important information about their probable toxicities. Drugs available in the combination may deposit slowly in the body and may lead to toxicities. Here an antihypertensive drug combination ‘Olmesartan medoxomil and Hydrochlorothiazide’ had been studied. Results Olmesartan medoxomil and Hydrochlorothiazide have not been found to comply any similar protein to interact with each other, thus no possible chance of additional toxicity of the combination in case of long term use. Conclusions At first, using PubChem the ligand was searched for a canonical SMILE. By inputting the canonical SMILE in Protox, a basic information about toxicities was predicted. From Swiss Target Prediction, target proteins responsible for both efficacy and toxicity were identified. These protein structures were downloaded from Protein Data Bank and edited with Flare. Undesired amino acid, ligand–ligand complex, fatty acid, and water molecules were removed by PyMOL. Structurally modified proteins and ligands were inputted in Swiss PDB viewer for energy minimization. Energy minimization is a very important step because unfavorable bond length, bond strength and torsion angle between protein and ligand may interfere with docking procedure. Then docking between Olmesartan medoxomil (ligand) and the proteins responsible for efficacy and toxicity was performed by PyRx. Vina binding affinity provided the value of binding strength between the ligand and the proteins, which determines how strong the bond is. The more negative the vina binding affinity, the stronger the bond. Discovery studio software was used to visualize the docking complexes. Same steps were followed for Hydrochlorothiazide to identify proteins responsible for desired and undesired effects, but no toxic effect was found from protox.

ANTIHYPERTENSIVE PHARMACOTHERAPY IN HYPERTENSIVE PATIENTS AT A TERTIARY CARE TEACHING HOSPITAL AND MEDICAL COLLEGE IN INDIA

Aim and Objectives: The aim of the study was to compare the efficacy of Atenolol and Olmesartan in Stage-1 hypertension (HTN), and the adverse effect profile of Atenolol and Olmesartan in Stage-1 HTN. Methods: A prospective, randomized, open, and parallel study was carried out in 100 patients attending the outpatient department of General Medicine Department MMIMSR, Mullana, Ambala, India with Stage -1 HTN according to joint national committee VII. The patients were randomly divided into two groups to receive Tab. Atenolol 50 mg od (Group A, n=50) and Tab. Olmesartan medoxomil 20 mg (Group B, n=50) od for a total period of 12 weeks with regular follow up every 2 weeks from the baseline. At each visit, blood pressure (BP), heart rate, and adverse effects were evaluated. Laboratory investigations were carried out at baseline and end of the study period. p<0.005 was considered statistically significant. Results: Atenolol and Olmesartan medoxomil both significantly reduce BP and heart rate (p<0.005). Olmesartan medoxomil is more efficacious in reducing BP. Conclusion: Olmesartan medoxomil is a better choice for Stage -1 HTN between the two drugs as it leads to a greater decrement in BP.

The Clinical Efficacy of Clopidogrel Bisulfate Tablets Combined with Olmesartan Medoxomil for Ischemic Stroke with Hypertension and the Effect of Angiotensin II Type 1 Receptor Level on Prognosis

Background. Ischemic stroke combined with hypertension can increase risks of stroke recurrence and death. Aim. The aim of this study is to investigate the clinical efficacy of clopidogrel bisulfate tablets combined with olmesartan medoxomil in the treatment of ischemic stroke patients with hypertension and the effect of angiotensin II type 1 receptor (AT1R) level on prognosis. Methods. Ninety ischemic stroke patients with hypertension were chosen for continuous treatment with clopidogrel bisulfate tablets and olmesartan medoxomil for 12 months. The Modified Edinburgh Scandinavian Stroke Scale (MESSS) score, Brunnstrom score, Barthel score, death, recurrence, and progression of cerebrovascular residual lesions were observed and recorded during the treatment period. According to the plasma AT1R expression of the patients before treatment, the patients were divided into a high-AT1R group and low-AT1R group. Then, survival analysis was performed. Results. Compared with pretreatment, the MESSS scores of the patients at the first, second, third, sixth, ninth, and twelfth months after treatment were reduced ( p < 0.01 ) while the Brunnstrom score and Barthel score were prominently boosted ( p < 0.01 ). Compared with the low-AT1R group, patients in the high-AT1R group had higher rates of stroke recurrence and progression of residual cerebrovascular lesions ( p < 0.05 ). Conclusion. Clopidogrel bisulfate tablets combined with olmesartan medoxomil has prominent clinical effects in the treatment of ischemic stroke patients with hypertension, evidently improving the prognosis. In addition, the level of AT1R may be a vital factor affecting the prognosis.