Formulation, optimization and evaluation of oral nanosuspension tablets of nebivolol hydrochloride for enhancement of dissoluton rate (original) (raw)
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International journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: Solubility is greater challenges for formulation which can be explain by different technological approaches during the pharmaceutical product development and to improve water solubility and drug release respectively. Methods: The solid dispersions of nebivolol were prepared in ratio 1:1, 1:3, 1:5 and 1:7 by fusion and solvent evaporation method using PEG 6000 and PVP K30 as carriers to enhance solubility of compound. Results: All the solid dispersions were evaluated for drug content, phase solubility, in vitro dissolution study. Deferential Scanning Calorimetric (DSC) and Fourier Transformer Infra Red (FTIR) showed no chemical interaction between the drug and its carriers. Solubility of PEG 6000 and PVP K30 indicates a linear relationship (AL Conclusion: The overall results showed that process of nebivolol transfer from water to carrier solution is more favorable at higher level of PVP K30. The solid dispersion of drug: PVP K 30 (1:7 ratio) prepared by solvent evaporation method was found to be optimum in term of solubility and dissolution rate. Hence, we can concluded that solubility of nebivolol can be enhanced using this carrier ratio. type of curve) in the investigated polymer concentration range. The Gibb's free energy showed declined trend with increase in the carrier concentrations. The uniformly of drug content was found in all solid dispersions. The drug release obtained from different drug-carrier concentration level fitted to different kinetic model and it was found that solid dispersions exhibited fickian diffusional characteristics and best fitted to higuchi model. A PVP K30 solid dispersion (1:7 ratio) prepared by solvent evaporation method showed faster dissolution rate (94.38 %) in 30 min among studied solid dispersions..
Enhancement of Solubility and Dissolution of Nebivolol by Solid Dispersion Technique
International Journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: Solubility is greater challenges for formulation which can be explain by different technological approaches during the pharmaceutical product development and to improve water solubility and drug release respectively. Methods: The solid dispersions of nebivolol were prepared in ratio 1:1, 1:3, 1:5 and 1:7 by fusion and solvent evaporation method using PEG 6000 and PVP K30 as carriers to enhance solubility of compound. Results: All the solid dispersions were evaluated for drug content, phase solubility, in vitro dissolution study. Deferential Scanning Calorimetric (DSC) and Fourier Transformer Infra Red (FTIR) showed no chemical interaction between the drug and its carriers. Solubility of PEG 6000 and PVP K30 indicates a linear relationship (AL Conclusion: The overall results showed that process of nebivolol transfer from water to carrier solution is more favorable at higher level of PVP K30. The solid dispersion of drug: PVP K 30 (1:7 ratio) prepared by solvent evaporation method was found to be optimum in term of solubility and dissolution rate. Hence, we can concluded that solubility of nebivolol can be enhanced using this carrier ratio. type of curve) in the investigated polymer concentration range. The Gibb's free energy showed declined trend with increase in the carrier concentrations. The uniformly of drug content was found in all solid dispersions. The drug release obtained from different drug-carrier concentration level fitted to different kinetic model and it was found that solid dispersions exhibited fickian diffusional characteristics and best fitted to higuchi model. A PVP K30 solid dispersion (1:7 ratio) prepared by solvent evaporation method showed faster dissolution rate (94.38 %) in 30 min among studied solid dispersions..
Pharmaceutical Nanotechnology, 2014
Nebivolol HCl (NBL) a third generation beta blocker poses lack of oral bioavailability (12%) owing to its low solubility and first pass biotransformation in liver. The present research was undertaken to prepare solid Selfnanoemulsifying drug delivery system (S-SNEDDS) of NBL which will present NBL at molecular level in nanoemulsion form throughout GIT. Increased solubility along with intestinal lymphatic transport of lipid rich nanoemulsified drug bypassing hepatic first pass may enhance bioavailability. Based on solubilization of the drug and spontaneity of selfemulsification, Peceol as an oily phase, Cremophore RH 40 and Gelucire 50/13 as surfactants and ethanol as cosurfactant/co-solvent were selected as the excipients to produce NBL loaded S-SNEDDS. Total 9 formulations were made with different ratios of the excipients and the optimized formulation was selected on the basis of solidification of SNEDDS on refrigeration and maintenance of the solid state. Spherical shaped morphology of oil globules was confirmed by TEM analysis. On dilution S-SNEDDS showed nanoparticles of size 180-190nm with a Polydispersity index 0.4-0.8 and Zeta potential-5.17,-7.56mV. The DSC and X-ray diffraction patterns of the S-SNEDDS show the amorphous state of NBL in the lipid matrix. Developed S-SNEDDS showed pH-independent drug dissolution which in SIF was fourfold greater as compared to plain drug. The intestinal permeability by everted sac technique showed threefold increase in transportation of NBL from S-SNEDDS formulation compared to NBL solid suggesting that S-SNEDDS of NBL is an excellent and practical approach of enhancing the oral bioavailability through improved solubility.
International Journal of Research in Pharmaceutical Sciences, 2021
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, disi...
2014
Nebivolol hydrochloride (NEB) is third generation beta-blocker, approved by the FDA to treat a hypertension. It’s a racemic mixture of a dNebivolol and l-Nebivolol. Oral delivery of the NEB shows a lower bioavailability due to its poor solubility and permeability. In a present study, solid self nanoemulsifying drug delivery (S-SNEDDS) is formulated to increase the bioavailability of drug by increasing solubility and permeability through the gastro intestinal membrane. The S-SNEDDS get formulated using Optimized SNEDDS formulation with the different adsorbent D-mannitol, Trehalose, and Lactose. Further, the effect of Dilution on the globule size, globule size and PDI, differential scanning calorimetry, Fourier transformed infrared spectroscopy of S-SNEDDS was studied. In-vitro drug release study was performed using dialysis bag method. Ex-vivo drug release studies were also carried out to determine the permeability of S-SNEDDS through the stomach and intestinal membrane. The best of ...
Brazilian Journal of Pharmaceutical Sciences, 2020
The objective of this study was to determine specific combination of pharmaceutical excipients that lead to formulation of efficient nebivolol hydrochloride SMEDDS and its subsequent formulation into IR-SET (Immediate release-Self emulsifying tablet) which will enhance its solubility and dissolution. Solubility and Pseudo-ternary phase studies were carried out to identify the excipients showing highest solubility and to identify the zone of microemulsion with selected ingredients. Liquid-SMEDDS (L-SMEDDS) were optimized for Concentration of oil(X1) and Smix(X2) and formulated using a combination of Kollisolv GTA as oil, Tween 80 as surfactant and propylene glycol as co-surfactant which gave smaller droplet size(Y1) 55.98nm , Emulsification time (Y2) 16±1.5 s,% transmittance (Y3) 99.94±0.47%. Neusilin US2 was used as solid carrier for solidification of L-SMEDDS in to Solid-SMEDDS (S-SMEDDS) by adsorption technique. IR-SET of nebivolol were formulated with S-SMEDDS and optimized for the concentration of binder (X1) (PVP K30) and superdisintegrant (X2) (KOLLIDON CL) which showed low Disintegration time (Y1) (92±0.5s) and low Friability(Y2)(0.424±0.03%). Also the DSC and XRD data revealed the molecular state of the drug in S-SMEDDS. The extent of in-vivo drug release and ex-vivo diffusion values from L-SMEDDS and IR-SET was much higher than pure drug and marketed tablet. In conclusion, the results showed potential of SMEDDS to improve solubility and thus the bioavailability.
DESIGN AND EVALUATION OF LIQUISOLID COMPACTS OF NEBIVOLOL HYDROCHLORIDE
International Journal of Applied Pharmaceutics, 2022
The aim of this study was to investigate the potential of a liquisolid system to improve the dissolution rate and the bioavailability of nebivolol hydrochloride. Methods: Solubility of nebivolol was determined in different nonvolatile solvents to finalize the best nonvolatile vehicle having maximum solubility. The liquisolid compacts were prepared using Fujicalin as a carrier material, Aerosil 200 as a coating material, Polyethylene glyc ol 400 as a liquid vehicle, and Croscarmellose sodium as a super disintegrating agent. 2 3 full factorial design was used to optimize the formulation in which the drug concentration, PVP K 30, Excipient ratio (R), and nebivolol containing nonvolatile solvent liquid level were selected as independent variables by using design expert software. The eight liquisolid compact formulations were prepared. Nebivolol liquisolid compacts were evaluated for drug content, tablet hardness, Friability, disintegration, and dissolution. An in vivo study was carried out in male Wistar rats. Results: The solubility of nebivolol hydrochloride in polyethylene glycol 400 was found to be greater than the other nonvolatile solvents. The liquisolid system of nebivolol was formulated successfully using Fujicalin, Aerosil 200, and polyethylene glycol 400. In vitro evaluation parameters for the liquisolid compact were within the prescribed limits. It was found that optimized liquisolid tablet formulation showed higher dissolution than the marketed tablet, with 88.33±0.94 % drug release within 120 min and the drug release was more than 75 % in 30 min for nebivolol LS-3N, which is optimized. LS-3N liquisolid compacts follow the Peppas model and exhibited first-order release. Conclusion: The liquisolid compacts can be a promising alternative for the formulation of water-insoluble drug nebivolol hydrochloride with improved dissolution and bioavailability.
Formulation and Evaluation of Bilayer Matrix Tablets of Nebivolol Hydrochloride and Valsartan
2019
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...
Solubility Enhancement of Nebivolol by Microemulsion Technique
Jhunjhunu, 2017
Nebivolol is a third-generation beta-a drenoceptor antagonist. It differs from other beta-a drenoceptor an tagonists as it combines highly selective beta (1)-adrenoceptor antagonist properties with nitric oxide-mediated vasodilator actions and beneficial effects on endothelial function. But this very useful drug use is limited due to challenge of poor water solubility (0.0403 mg/ml). Present study deals with enhancement of solubility of Nebivolol by micro emulsion technique. Various oils, surfactants, and co-surfactants were used to check solubility of Nebivolol. Pseudoternary phase diagrams were constructed using various combinations of ingredients i.e. oil: surfactant: co-surfactant. Micro emulsion batches were prepared by phase titration method. Developed micro emulsion was evaluated for various physicochemical, stability parameters, in-vitro and ex-vivo parameters. Results showed stable micro emulsion form of Nebivolol improved solubility.
Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs
International Journal of Pharmaceutics, 2006
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.