Hypertension

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.

The present study aimed at improvement of solubility and bioavailability of Lercanidipine HCl using self-nanoemulsifying drug delivery systems (SNEDDS). The extent of self-emulsification was checked with various oils with suitable surfactants and co-surfactants. The final optimized formulation contained Caproyl 90, Tween 80 and Labrosol as oil, surfactant and co-surfactant respectively. Based on Lercanidipine solubility analysis, ternary phase diagrams were constructed for optimizing the system. The formulations were evaluated for solubility, droplet size determination, zeta potential and stability studies. The droplet size was found to be 5.1 nm & Z-Average of 14.6 nm. The zeta potential of the optimized formulation (F16) was found to be -19.7 mV. In vitro drug release from SNEDDS was significantly higher than pure drug. From in vivo bioavailability studies the optimized formulation was exhibited a significantly greater Cmax (56.2±0.04ng/ml) than the pure drug suspension (35.1±0.03ng/ml). AUC0-∞ for SNEDDS formulation was higher (190.5±2.04 ng.h/ml) than the pure drug suspension 145.7±2.02ng.h/ml. Statistically, AUC0-t of the SNEDDS formulation was significantly higher (p<0.05) as compared to pure drug suspension formulation. The study demonstrated that SNEDDS was a promising strategy to enhance the solubility and oral bioavailability of Lercanidipine.

In current investigation an attempt has been made to formulate and evaluate Quinapril mouth dissolving films using HPMC 50cps, E5, E15 and in combination of Pullulan by Solvent evaporation method. Sodium starch glycolate acts as a super disintegrating agent and it is shown that as the concentration of the super disintegrates increases the disintegration time decreases. The films were evaluated for weight variation, surface pH, folding endurance, drug content, dissolving time, disintegration time, and in-vitro dissolution studies. Based on the evaluation parameters F17 was to be optimized formulation. The optimized film (F17) showed the more drug release i.e 99.40±5.30% within 7 min, lowest in vitro disintegration time 10 sec. FTIR studies proved no drug polymer interaction takes place. From in vivo bioavailability studies, Cmax of the optimized formulation F17 was 72.43±0.3ng /ml, was significantly higher as compared to pure drug suspension, i.e., 42.32±0.1ng/ml. Tmax of optimized formulation was decreased significantly when compared with pure drug (1.00±0.05hr, 2.00±0.1hr), AUC0-∞ and AUC0-t for optimized films was significantly higher (p<0.05) as compared to marketed product. These results revealed that fast dissolving films of Quinapril could be formulated for quick onset of action which is required in the efficient management of hypertension.

The study was aimed to formulate solid dispersions of Manidipine by using different novel carriers like Labrafac PG, Kolliwax RH 40, Soluplus, Kolliwax GMS II, Kolliphor EL and SLS in drug carrier ratio by using solvent evaporation method. The formulations were characterized for physical appearance, solubility and in vitro dissolution studies. The optimized formulation was characterized by, Formulation SD13 was found to be optimized one based on the solubility, dissolution and other parameters using Kolliwax GMS II and SLS.  The drug release of the optimized formulation was found to be 99.41±5.38% within 90min. Powder X-ray diffraction studies performed on solid dispersion showed that Manidipine existed in the amorphous form within the solid dispersion formulation fabricated using the solvent evaporation process. Additionally, scanning electron microscopy studies suggested the conversion of crystalline Manidipine to an amorphous form. Furthermore, the pharmacokinetic parameters of the optimized Manidipine solid dispersions showed increased AUC0–t, AUC0–∞ and Cmax by 2-folds. These results suggest that the preparation of Manidipine solid dispersions using the solvent evaporation technique without might be a promising approach for improving the oral bioavailability of Manidipine. Therefore, the solid dispersions using Kolliwax GMS II as hydrophilic carrier in the combination of SLS can be successfully used for improvement of solubility and bioavailability of Manidipine.

Nimodipine, a poorly soluble drug, was considered to be fit for solid dispersions to improve its solubility and bioavailability. Our study intended to prepare Nimodipine solid dispersions by solvent evaporation method using various novel polymers. Solubility and dissolution studies indicate that Kolliwax RH 40 and SLS is the most suitable polymer. The solubility studies were corresponded with dissolution data and the formulation SD15 was found to be having highest drug release of about 98.96±5.15% in about 90 minutes. In-vitro release data from several formulations containing XRD and SEM studies indicate no crystallinity in the optimized formulation SD15. FTIR studies suggested good drug excipient compatibility between all components of prepared formulation. From in vivo bioavailability studies, Cmax of the optimized formulation SD15 was 4.34±0.08ng /ml, was significantly higher as compared to pure drug suspension, i.e., 2.78±0.35ng/ml. Tmax of optimized formulation was decreased significantly when compared with pure drug (1.00±0.05hr, 2.00±0.01hr), AUC0-? and AUC0-t for optimized solid dispersion formulation was significantly higher (p<0.05) as compared to pure drug suspension. The present study demonstrated that formulation of Nimodipine solid dispersion by solvent evaporation technique is a highly effective strategy for enhancing the bioavailability of poorly water soluble Nimodipine.

The main goal is to identify suitable to their Anti-hypertensive activity with reference (Clonidine Standard drug). Pubchem webserver, Chemsketch, Padel descriptor, Protein data bank (PDB), Autodocktools, E-dragon webserver. To generate the Scaffold molecule. To calculate different parameters of test sample with its biological activity. To fit the final series of compound with particular target. To predict ADMET of final series of compound. After substitution R1 & R2 of test sample we have found that the value of different descriptors of QSARs is nearby equal to standard drug of clonidine. All the descriptors are (QSARs parameters) of Scaffold molecule H1 was satisfactorily explained (R2 = Approximately 0.99) with the graphical plot of Hansch analysis. This compound had very poor blood brain barrier crossing label, good absorption, no hepatotoxicity, no mutagenecity. Beside this compound was non-carconogenic after in-silico predictions of ADMET. 

Diabetes mellitus and Hypertension are a common disease that is suffered by a huge percentage of total population. The coexistence of these two diseases is at a greater frequency than alone. Hypertension in the diabetic individual potently increases the risk and accelerates the risk of cardiac disease, stroke, peripheral vascular disease, nephropathy and retinopathy. The management of both this disease is equally important and the reduction in cholesterol level have significant role in preventing diabetic complication. Diabetic associated diseases like nephropathy also lead to the development of hypertension particularly in type I diabetic patient. The coexistence of hypertension in both type I and type II diabetic patients can lead to be increased peripheral vascular resistance and the exchangeable sodium ion can be a reason for hypertension in diabetics. The insulin resistance or hyperinsulinemia or elevated insulin can be one of the major pathogenesis of hypertension. In the present study we have reviewed the various literatures related to the coexistence of to life threatening disease that is hypertension and diabetic and it was observed that these two diseases are most commonly associated in a person. Thus there should be some modified treatment procedures for this kind of life threatening associated diseases.   

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.

Hypertension is the most important risk factor for cardio vascular disease. But, the key question remains: which of the many available types of blood pressure lowering drugs is the better choice as first line medication. Hence, the prospective, randomized, single blind , Comparative study was conducted  at tertiary care Hospital to  assess  the beneficial outcomes of drugs by comparative method. The study concludes that the physicians were prescribed the ACEIs for hypertension with various co morbidities as per JNC-7 guidelines. The study conclude that the A+E+N is the most effective combination therapy for better control of hypertension. The study indicates that the combination therapy can be individualized according to the presence of co morbidities  with  HTN.

Triamterene is a potassium-sparing diuretic which is commonly used in combination with Hydrochlorothiazide, a thiazide-type diuretic in clinical management of edema and moderate hypertension. In this study, a rapid and sensitive LC–MS/MS method was developed and validated for determination of Triamterene and Hydrochlorothiazide from K3EDTA based Human Plasma. Triamterene D5 and Hydrochlorothiazide 13C6 were used as an Internal Standards for analysis of Plasma Samples.  The analytes and internal standards, were extracted by liquid–liquid extraction method using Se Quant®ZIC-HILIC, (5um,200A 150 X 4.6 mm)  column with Acetonitrile and 2 mM Ammonium formate containing 0.1% formic acid (80:20 v/v) as the mobile phase. Linearity was assessed from 3.10ng/mL to 229.72 ng/mL for Triamterene and 5.47 ng/mL to 405.27 ng/mL for Hydrochlorothiazide in plasma.  No significant matrix effects were observed by analysing the plasma samples on LC–MS/MS. The accuracy was in the range of 98.32 % to 102.86 % for both compounds. Triamterene and Hydrochlorothiazide were found to be stable up to 120 days in K3EDTA based Human Plasma at -20ºC. The stability of Triamterene and Hydrochlorothiazide in plasma was confirmed up to five freeze-thaw cycles (−20°C) and on bench up to 25 hours. The proposed bioanalytical method for the quantitation of Triamterene and Hydrochlorothiazide from K3EDTA based human plasma samples was satisfactorily validated. It can be used to include study data for quantitation of Triamterene and Hydrochlorothiazide from K3EDTA based human plasma in bioequivalence and bioavailability study.