Novel Determination of Anti-Hypertensive Combination; Benidipine Hydrochloride and Nebivolol Hydrochloride by High Performance Chromatographic Method

This research work was designed to establish and validate a novel stability indicating RP-HPLC method for the combined determination of Benidipine hydrochloride (BHE) and Nebivolol hydrochloride (NHE) in bulk and tablets, dependent on ICH guidelines.The assay method to analyse BHE and NHE was optimized with isocratic elution using acetonitrile: 0.1M acetate buffer (45:55, pH 5.1), Lichrospher ODS RP-18 column and flow pace of 1 ml/min. Total time for single run was 14 min. The injection quantity was 20μl, and was detected at 249nm. The method was verified on a concentration series of 1.25-10μg/ml (NHE) and 1.0-10μg/ml (BHE) for precision, accuracy and linearity. The LOD values were 0.059µg/ml and 0.028µg/ml for NHE and BHE, respectively. The LOQ values were 0.196µg/ml for NHE and 0.094µg/ml for BHE. The recovery percentages were 98.60-100.11% (BHE) and 98.94-101.50% (NHE) with relative standard deviation 0.250-0.694% (BHE) and 0.183-0.400% (NHE). The method was also observed to be efficient, and was sufficiently specific to measure BHE and NHE in the presence of stress-produced degradation products.

Effect of Hydroxypropyl Methylcellulose and Microcrystalline Cellulose in Design and Optimization of Nebivolol Hydrochloride Immediate Release Tablets by Response Surface Methodology

The goal of the research is to design and optimize Nebivolol Hydrochloride immediate-release tablet using response surface methodology. Nebivolol Hydrochloride immediate-release tablets used in the treatment of heart attacks, myocardial infarction. Response surface methodology calculations for this optimization study were performed utilizing Minitab 17. Different formulations of immediate-release were prepared by applying 2 factors 3 levels full factorial design using Minitab 17, which gave 9 formulations by using the wet granulation method. Independent variables like the amount of hydroxypropyl methylcellulose (X1), and microcrystalline cellulose (X2) and dependent variables like the per cent drug release at 45 minutes (Y1), disintegration (Y2) were selected for optimization. The prepared batches of Nebivolol Hydrochloride immediate-release tablets were evaluated for the pre-compression and post-compression parameters like weight variation, thickness, hardness, and friability, disintegration, and in-vitro drug release studies. All the Physico-chemical parameters were found satisfactory for prepared tablets. The optimized formulation F7 showed disintegrated in 83 sec, percentage dissolution release 97.85 at the end of 45th minute. The results shows that formulated immediate-release tablets of Nebivolol HCl were better to meet patient compliance with respect to effectiveness.

Investigation of the Potential of Nebivolol Hydrochloride-Loaded Chitosomal Systems for Tissue Regeneration: In Vitro Characterization and In Vivo Assessment

In this study, we evaluated the synergistic effect of nebivolol hydrochloride (NVH), a third-generation beta-blocker and NO donor drug, and chitosan on the tissue regeneration. Ionic gelation method was selected for the preparation of NVH-loaded chitosomes using chitosan lactate and sodium tripolyphosphate. The effect of different formulation variables was studied using a full factorial design, and NVH entrapment efficiency percentages and particle size were selected as the responses. The chosen system demonstrated high entrapment efficiency (73.68 ± 3.61%), small particle size (404.05 ± 11.2 nm), and good zeta potential value (35.6 ± 0.25 mV). The best-achieved formula demonstrated spherical morphology in transmission electron microscopy and amorphization of the crystalline drug in differential scanning calorimetry and X-ray diffraction. Cell culture studies revealed a significantly higher proliferation of the fibroblasts in comparison with the drug suspensions and the blank formula. An in vivo study was conducted to compare the efficacy of the proposed formula on wound healing. The histopathological examination showed the superiority of NVH-loaded chitosomes on the wound proliferation and the non-significant difference in the collagen deposition after 15 days of the injury to that of intact skin. In conclusion, NVH-loaded chitosomes exhibited promising results in enhancing skin healing and tissue regeneration.

SOLID DISPERSION OF NEBIVOLOL HYDROCHLORIDE IMPREGNATED BUCCAL PATCH: FORMULATION AND CHARACTERIZATION

Objective: The objective of the present investigation was to design and characterize a mucoadhesive buccal patch of Nebivolol hydrochloride in order to administer a small dose of a drug to treat hypertension effectively and thereby avoiding disadvantages such as patient noncompliance and low bioavailability. Methods: The buccal patches were prepared by solvent casting method. The polymers used to formulate patches were HPMC K 15 M, PVP K 30, and propylene glycol was used as plasticizer and ethanol as the solvent. The drug-polymer compatibility studied was conducted by FTIR. Results: All the developed Patches had good transparency and stability. All formulated patches showed pH in the range of 6.49 to 7.22, and drug content was more than 90%. The folding endurance value showed that the patches are flexible and non-brittle. The in vitro residence time was found to more than 30 min. Thickness, % moisture absorption, and % moisture loss values were in a normal range. The drug release study was conducted for 8 h, and it was found drug release was decreased with the increase in polymer concentration. The in vitro release profiles of the drug from all the formulations appeared to follow Korsmeyer Peppa's exponential model, and release exponent (n) was found to be more than 0.45 so that the release can be characterized by Non–Fickian (anomalous) diffusion. Conclusion: From the results, it was concluded that drug released from formulated buccal patches follows sustained release pattern, Hence can be used for the treatment of the hypertensive patient.

Spectrophotometric Method Development and Validation for Simultaneous Estimation of Nebivolol hydrochloride and Valsartan in Bulk and Combined Pharmaceutical Dosage Form in Release Media

A simple, rapid, precise, accurate and sensitive spectrophotometric method has been developed for the simultaneous estimation and validation of Nebivolol Hydrochloride (NEB) and Valsartan (VAL) in pure and combined tablet dosage forms. Pure drug samples of NEB and VAL were dissolved in 67 mM Phosphate buffer pH 6.8 with 0.5% sodium dodecyl sulphate (SDS) and found to have absorbance maxima at 280 nm for NEB and 250 nm for VAL, respectively. The linearity lies between 10-70μg/ml for NEB and 10-60μg/ml for VAL in this method. The correlation coefficient (r2) was found to be 0.9965 for NEB and 0.9960 for VAL. The % recoveries obtained were 95.65%-109.85% for NEB and 97.42%-101.43% for VAL. The % RSD found 0.271%-1.490% for intraday and 0.334%-1.917% for interday for NEB and 0.188%-0.944% for intraday and 0.392%-1.197% for interday for VAL. The limit of detection and limit of quantitation for NEB were found to be 4.608μg/ml and 13.965μg/ml respectively and the limit of detection and limit of quantitation for VAL were found to be 4.348μg/ml and 13.178μg/ml respectively. Simultaneous calibration of both drugs in 67 mM Phosphate buffer pH 6.8 with 0.5% SDS shows that λmax of one drug does not interfere on the λmax of other drug. Recovery study was performed to confirm the accuracy of the method. The results of analysis have been validated statistically by recovery studies as per International Conference on Harmonization guidelines. The method showed good reproducibility and recovery with % RSD Lessthan 2. Hence, this proposed method was found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of NEB and VAL in pure and combined tablet dosage form.

Comparative Study of Antihypertensive Drugs Amlodipine Besylate /Metoprolol Succinate and Nebivolol Hydrochloride /Valsartan Combinations in Bilayer Tablets

The present research is an approach to develop a formulation platform that shall help in minimizing the time and effort taken to develop a drug delivery system. Taking bilayer tablet technology as a representation for drug delivery system, well accepted antihypertensive drugs, Amlodipine besylate and Metoprolol succinate were considered as model drugs for the study. Initially the process variables like concentration of the disintegrants, Sodium starch Glycolate and cross carmellose sodium, Polymers HPMC K100M and K4M were standardized with these drugs so that the incorporation of a new combination drugs would provide predictable results with a minimal trial runs. Nebivolol hydrochloride and Valsartan were considered as test drugs since they are novel antihypertensive drug combination and their physicochemical and pharmacokinetic parameters were almost similar to that of the model drugs. The r value 0.98943 indicates a good correlation between the release profile of Amlodipine besylate (model drug) and Nebivolol hydrochloride (test drug) from the IR layer. Similarly, the r value in the range of 0.9998 indicates a good correlation between the release profile of Metoprolol succinate (model drug) and Valsartan (test drug) from the SR layer. The comparable experimental results of the model drugs and test drugs considered for this study infer that if two drugs are similar in their physicochemical and pharmacokinetic parameters, their behavior with respect to in vitro parameters will be similar provided formulation variables remains constant. This concept could be productive in developing drug delivery system for new drugs for which extensive research and time are major constraints. Keywords: Bilayer tablets, fixed unit dosage form, Amlodipine besylate, Metoprolol Succinate Nebivolol hydrochloride, Valsartan.

Formulation and Evaluation of Bilayer Matrix Tablets of Nebivolol Hydrochloride and Valsartan

The present study is an attempt to develop bilayer matrix tablets of Nebivolol Hydrochloride and Valsartan with immediate release for Nebivolol Hydrochloride and sustained release for Valsartan. Superdisintegrants such as sodium starch glycolate and Crosscarmellose sodium were evaluated for immediate release of Nebivolol Hydrochloride and polymers HPMC K100M and K4M for sustained release of Valsartan. Preformulation studies were performed prior to compression. The compressed bilayer tablets were evaluated for weight variation, thickness, hardness, friability, drug content and in vitro drug release using USP dissolution apparatus type 2 in 0.01N HCl and phosphate buffer pH 6.8. All the pre and post compression parameters were found to be within the acceptable limits. The results of dissolution show that the formulations B3 was the best of all immediate and sustained release layer batches. The release kinetics of Valsartan was subject to curve fitting analysis in order to identify the best fit kinetic model. The regression analysis proves that the best formulations follow zero order release and drug release by diffusion process based on Fick’s law of diffusion. The data for stability studies infer no considerable change in drug content and dissolution rates as per ICH guidelines. The best formulation B3 was subjected to in vivo pharmacokinetic studies in rabbit model. In vitro, In vivo correlation (IVIVC) showed considerable linearity. Hence a novel bilayer tablet formulation of Nebivolol Hydrochloride and Valsartan was successfully developed by combining both immediate (IR) and sustained (SR) release layers. Keywords: Bilayer tablets, fixed unit dosage form, Nebivolol hydrochloride, Valsartan, LC-MS analysis.