Labetalol HCl Research Articles

Formulation and evaluation of extended-release floating tablets of labetalol hydrochloride 200 mg

The aim of present work is to formulate and evaluate extended-release floating tablets of Labetalol HCL to improve the bioavailability, Patient compliance and solubility on oral floating drug of Labetalol HCL. Labetalol HCL is mainly used in the treatment of hypertension, which is BCS Class Ⅰ drug i.e. Highly soluble and highly permeable. The tablets were prepared by wet granulation method by using different concentrations of HPMC polymer. The tablets were evaluated for Preformulation characteristics, Pre compression parameters and post compression parameters. In-vitro dissolution studies were performed for all prepared formulations by using dissolution test apparatus employing a paddle stirrer at 50 rpm and 37 ± 0.5°C, 0.1N HCL buffer was used as dissolution medium. Samples of 5ml each were withdrawn at different time intervals. Each sample withdrawn was replaced with an equal amount of fresh dissolution medium. Samples were diluted and assayed at 302 nm using Agilent UV Visible double beam spectrophotometer. The increased drug release is due to the presence of low concentration of HPMC K4 m. The drug release kinetics was calculated for all the formulations, among all the formulations F8 was taken as optimized formulation whose percentage drug release was found to be 96%. It indicates the release follows zero order and Hixon kinetics. Hence formulation F8 was Considered as the optimized batch and stability studies were conducted at 40oc±2oc/75±5%RH, Storage condition for 3 months and no change was observed.

Development and In-Vitro Evaluation of Plantago ovata Based Rapid Disintegrating Tablets of Labetalol Hydrochloride

Objectives: To avoid swallowing problems of conventional tablets and improved patient compliance Plantago Ovata based Labetalol HCl Rapid disintegrating tablets have been prepared. Methods: Six different (F1 to F6) batches of Labetalol HCl Rapid disintegrating tablets were developed by ‘direct compression method’ using Plantago ovata as a natural super-disintegrating agent. The formulated RDT were tested for angle of repose’, densities like tapped and bulk density, Hausner’s ratio, Carr’s index like pre-compression parameters and for thickness, weight variation or weight uniformity, tablet hardness, % drug content or content uniformity, water absorption ratio’, time require for wetting of tablets’ means wetting time, in-vitro drug disintegration time and in-vitro drug dissolution studies under post-compression parameters of evaluation. Results: It was found that the all the results of these pre-compression and post-compression parameters comply with official standards. The drug release was determined using dissolution media of pH 6.8 phosphate buffer through in-vitro dissolution of drug. This study showed that a rapid drug release by prepared tablets. The optimized formulation F6 showed higher water absorption ratio`, lower wetting time, minimum in-vitro disintegration time’ and higher drug release amongst all the formulations. The F6 formulation was considered the best among all formulations. Conclusion: The prepared rapid disintegrating tablets shows rapid onset of action by quick drug release, minimize side effects and enhanced patient compliance. These prepared tablets containing selective alpha-1 and non-selective beta adrenergic antagonist’ drug candidate Labetalol HCl, will be very useful in the treatment of high blood pressure with enhanced bioavailability.
 Keywords: Rapid disintegrating tablets, Labetalol Hydrochloride, Bioavailability Enhancement, Natural Superdisintegrant, Plantago Ovata, High Blood Pressure, RDT, Patient Compliance

The Outcome of Lignocaine HCL, and Labetalol HCL in Low Doses for Attenuation of Hemodynamic Response to Laryngoscopy and Intubation

Background: Recently lower dosages of lignocaine and labetalol have been proven to be beneficial in reducing perioperative adverse cardiovascular events. Objective: In this study our main goal is to evaluate the outcome of lignocaine HCL, and labetalol HCL in low doses for attenuation of hemodynamic response to laryngoscopy and intubation. Method: This prospective study was done at tertiary hospital from January 2020 to December 2021. In this study 100 consenting patients of age group 31–60 years of either sex and various general surgical procedures under endotracheal anesthesia were included in this study. During the study, 100 patients were randomly divided into two groups depending on the study drug to be given: Group LB: Injection labetalol HCL 0.25 mg/kg body weight diluted to 10 ml with 0.9% saline was given IV 5 min before intubation over 60 s, n=50 and Group LG: Injection lignocaine HCL 1 mg/kg body weight diluted to 10 ml with 0.9% saline was given IV 5 min before intubation over 60 s, n=50. Results: during the study, majority were belonged to 41-50 years age group and 60% were male. The increase in mean HR was observed in LG groups but least in labetalol group. Besides that, increase in SBP in group lignocaine but not in labetalol group whereas DBP increased in all both groups almost similarly. RPP in peri-intubation period was most stable in group LB whereas mean atrial pressure increase in group LG was higher than that in group LB. Conclusion: Labetalol was found to be superior for the reduction of HR, SBP, DBP, mean arterial pressure, and RPP during and after laryngoscopy and endotracheal intubation in both intra- and inter-group comparisons.

A Oral Fast Dissolving Films Containing Lyophilized Labetalol HCL with Hydroxy Propyl β-Cyclodextrin/ Soluplus: Formulation Development, In Vitro Evaluation

Introduction: Labetalol HCL is an antihypertensive drug used to treat high blood pressure in the long term management of angina. Labetalol HCL is readily absorbed after oral administration. Labetalol HCl undergoes considerable hepatic first-pass metabolism due to its lipid-soluble nature. 
 Objective: The drug has an absolute bioavailability of approximately 25%. To overcome extensive hepatic first-pass metabolism the oral fast-dissolving film for labetalol HCL need to be developed. Lyophilized inclusion complexes of Labetalol HCL were developed with the hydrophilic carrier as Soluplus a Polyvinyl acetate polyethene glycol graft copolymer and Hydroxy Propyl β-cyclodextrin.
 Experimental: Lyophilized inclusion complexes of labetalol: Soluplus and labetalol HCL: HP-β-CD were prepared with 1:0.5 weight ratios. The prepared lyophilized inclusion complexes were evaluated for solubility estimation, drug content, and In-vitro dissolution study. 
 Results: The prepared inclusion complexes were characterized by Fourier transforms infrared spectroscopy and differential scanning calorimetry. Characterization of the lyophilized complex showed changed crystallinity of labetalol HCL. The fast dissolving oral film of labetalol HCL was prepared by solvent casting method by adding film-forming polymer as HPMC K 4M/ PVA in different proportions and Propylene Glycol was used as a plasticizer. The prepared batches of films were evaluated for weight variation, tensile strength, folding, endurance, disintegration time, surface pH, and drug content uniformity. All formulations prepared among F5 and F 7 showed a better result as compared to other formulations. 
 Conclusion: The study confirms the use of a lyophilized product containing Soluplus is best as that of HP-βCD for the preparation of fast dissolving film with HPMC/ PVA as film forming agent and propylene glycol as plasticizer respectively to improve dissolution rate and oral bioavailability of Labetalol HCl.

Design, Formulation Development and Evaluation of Matrix Tablet Containing Labetalol HCL

Design, Formulation Development and Evaluation of Matrix Tablet Containing Labetalol HCL

Design and Characterisation of Bi-layer Tablets Containing Simvastatin as Sustained Release and Labetalol HCl as Immediate Release

The objective of present investigation is to design and characterise sustained release Simvastatin and immediate release of Labetalol HCl, a bi-layer tablet. The combination therapy of Simvastatin and Labetalol HCl can be useful in severe cardiovascular disease such as hypertension, angina pectoris, congestive heart failure which may occur along with increasing cholesterol level in the blood, while this combination remain preferable choice to the patient as compared to single dosage form. The bi-layer tablet is suitable for sequential release of two drugs in combination which are compatible with each other. Objective of present investigation is to prepare bi-layer tablet in which one layer is sustained while another one is immediate release. For the preparation of bi-layer tablet, different super disintegrants like cross carmellose cellulose, micro crystalline cellulose is used for immediate release and HPMC and Carbapol as controlled release polymer. The pre-formulation parameter such as solubility, melting point, compatibility study (FTIR) were studied. Pre-compression parameter such as angle of repose, bulk density, tapped density, hausner’s ratio and compressibility index were studied. The tablets were evaluated by physical and chemical parameters such as weight uniformity, hardness, thickness, diameter, friability, drug content, disintegration time and in-vitro drug release. The dissolution data were subjected to various release kinetic model to recognize the mechanism of drug release. Keyword: sustained release tablet, bi-layer tablet, Simvastatin, Labetalol HCl.

Stability of regularly prescribed oral liquids formulated with SyrSpend® SF.

The purpose of this research was to evaluate the stability of 12 oral liquid formulations frequently compounded in hospital and community settings formulated in a specific vehicle: SyrSpend® SF. The stability of melatonin, glycopyrrolate, ciclosporin, chloral hydrate, flecainide acetate, tiagabine HCl, labetalol HCl, ciprofloxacin HCl, spironolactone/hydrochlorothiazide, hydrocortisone, itraconazole and celecoxib in SyrSpend SF PH4 (liquid) was investigated at 0, 30, 60 and 90 days and stored at both controlled room temperature and refrigerated. Itraconazole samples were also investigated at 15 and 45 days. No change in odor, color or appearance was observed in the formulations during the test period. Based on the results, a beyond-use date of 30 days can be assigned to tiagabine HCl 1.0 mg/ml in SyrSpend SF when stored at controlled room temperature, and 90 days under refrigeration, improving stability data previously published using other vehicles. A beyond-use date of 60 days can be assigned to chloral hydrate 100.0 mg/ml. In this case, stability is not enhanced by refrigeration. With the rest of the formulations, less than 10% API loss occurred over 90 days at either controlled room temperature or under refrigeration. Including for example itraconazole 20.0 mg/ml, thus providing extended stability compared to simple syrup and other oral liquid vehicles. The findings of this study show that SyrSpend SF is an appropriate suspending vehicle to be used for personalized formulations of the APIs studied here.

Limited Influence of Excipients in Extemporaneous Compounded Suspensions.

Objective: The objective of this study was to identify whether compounding oral suspensions with SyrSpend SF based on tablets or capsules is a suitable alternative for using raw pharmaceutical materials. Methods: Suspensions based on 5 different tablets and capsules were studied in SyrSpend SF. The summary of product characteristics of these different tablets and capsules were obtained from the manufacturer. Our hypothesis was that, if the maximum beyond-use date of the study was reached, the excipient did not seem to have an influence on the stability of the active pharmaceutical ingredient (API) within the studied time frame. Results: All excipients used in flecainide acetate, labetalol HCl, and tiagabine HCl tablets as well as in celecoxib and oseltamivir capsules did not seem to influence the beyond-use date of the overall suspension based on SyrSpend SF. Conclusion: Although using raw materials as API sources is preferred, oral suspensions with SyrSpend SF prepared from crushed tablets or opened capsules could be a possible alternative. Based on this study, a wide range of different excipients does not seem to impact the beyond-use date of different APIs compounded in SyrSpend SF.

A Comparative Study of Intravenous Esmolol, Labetalol and Lignocaine in Low Doses for Attenuation of Sympathomimetic Responses to Laryngoscopy and Endotracheal Intubation.

Background:Direct layngoscopy and endotracheal intubation is a noxious stimuli and induces sympathomimetic responses. Although well tolerated in healthy subjects, it may impose life threatening arrhythmias, left ventricular failure or rupture of cerebral aneurysm in susceptible patients. Esmolol, Labetalol and Lignocaine attenuate these responses but are associated with side effects of bradycardia, hypotension etc. In lower doses, chances of these side effects are comparatively low. So we designed this prospective clinical trial to assess the efficacy of intravenous esmolol, labetalol and lignocaine in low doses for attenuation of sympathomimetic responses to endotracheal intubation.Materials and Methods:Seventy-five consenting patients of ASA physical status I or II of age range 20 to 60 years, scheduled for different general surgical procedures were randomly assigned to one of the three groups; group ES, group LB and group LG. Participants of group ES, group LB and group LG was given esmolol HCL 0.5 mg/Kg, labetalol HCL 0.25 mg/kg and lignocaine HCL 1 mg/Kg body weight respectively. Outcome variables were HR, SBP, DBP, MAP and RPP. These variables were recorded just after intubation and thereafter at 1,3,5, 7 and 10 minutes of intubation.Results:There was no statistically significant difference regarding the demographic characteristics of the groups. Heart rate and systolic blood pressure was lower throughout the study period in labetalol group. But the values of study parameters were always higher than the baseline in esmolol and lignocaine group. Values of mean arterial pressure was slightly higher in labetalol group but it was much higher in two other groups throughout the study period. Diastolic blood pressure was higher in all the groups. Values of rate pressure product was higher during intubation and at 1minute after intubation in labetalol group but thereafter it was always lower than baseline values.Conclusion:Labetalol 0.25 mg Kg-1 is an effective and safe drug to be used for attenuation of sympathomimetic responses to endotracheal intubation. Esmolol 0.5 mg Kg-1 and lignocaine 1 mg Kg-1 are also effective to some extent and are safe.

Formulation and Evaluation of Controlled Release Matrix Tablets of Labetalol HCl

Oral controlled drug delivery systems have received much attention of the researchers during the past two decades. The rationale for developing a controlled release formulation is to enhance its therapeutic benefits, reducing its side effects and improving the management of diseased condition.

Formulation andin vitroEvaluation of Mouth Dissolving Tablets of Labetalol HCl by Sublimation Method

The objective of this research was to formulate fast dissolving tablets of Labetalol HCl that disintegrate in the oral cavity upon contact with saliva and there by improve therapeutic efficacy. Fast dissolving tablets of Labetalol HCl were prepared by direct compression method by using sublimation method. Seven formulations were prepared and evaluated for hardness, thickness, friability, weight variation, drug content, in vitro disintegration time, in vitro dispersion time, wetting time, water absorption ratio and in vitro dissolution studies. FTIR and DSC studies revealed that there was no chemical interaction between the drug and the excipients. Formulation S5 were found to be the best on the basis of wetting time, in vitro disintegration time and in vitro drug release. The formulation S5 containing Crospovidone as superdisintegrant and ammonium bicarbonate as subliming agent were found to be the optimized combinations. Stability studies were carried out for S5 at 400C±20C/75%±5% RH for 60 days. The results of stability studies indicated no significant changes with respect to physicochemical properties, in vitro disintegration time, wetting time and in vitro drug release.

Evaluation of a capillary electrophoresis method for routine determination of varenicline tartrate in quality control laboratories

<p class="Body"><span lang="EN-US">In this study, analyses were carried out in a fused-silica capillary (i.d. 50.0 µm, total length 48.5 cm and effective length 40.0 cm), in normal mode, applying a voltage of 20 kV. Sample injections were made in a hydrodynamic mode over 7 seconds under a pressure of 50 mbar. Capillary temperature was set at 35 <sup>°</sup>C and the detection was performed at 205 nm wavelenght. Background electrolyte was </span><span lang="EN-US">40 mM citrate buffer at pH 6.0 and the internal standard was labetalol HCl. Total analysis time was shorter than 5 minutes. The method was validated according to the ICH guidelines and it was found to be linear, precise, accurate, specific, robust and rugged. Linearity range was found to be </span><span lang="EN-US">1.0 – 60.0 µg mL<sup>-1</sup> and the limit of detection and quantitation were found as 0.5 and 1.0 µg mL<sup>-1</sup>, respectively. </span></p><p class="Body"><span lang="EN-US"> </span></p>

FORMULATION AND EVALUATION OF ORODISPERSIBLE LABETALOL TABLET FOR HYPERTENSIVE CRISIS

Labetalol HCl competitively blocks adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. Mouth dissolving drug delivery systems (MDTs) have acquired an important position in the market by overcoming previously encountered administration problems and contributing to extension of patent life. MDTs have the unique property of rapidly disintegrating and/or dissolving and releasing the drug as soon as they come in contact with saliva, thus obviating the requirement of water during administration. Taste masking was done by using Kyron-T 134 in ratio 1:3. The tablets were prepared by using direct compression method, using different Superdisintegrantsand they were then evaluated for pre and post compression parameters. More than 80% of drug was released from almost all the formulations within 5 min. Results of this study indicate among the superdisintegrants tried, Indion-414 showed the best result in 2% concentration.

Spectrophotometric Determination of Labetalol and Lercanidipine in Pure Form and in Pharmaceutical Preparations Using Ferric-1,10-Phenanthroline

A simple and sensitive spectrophotometric method was developed for the determination of labetalol HCl (LBT) and lercanidipine HCl (LER) in pure form and in dosage forms. The method was based upon oxidation of the LBT and LER with Fe+3 and the estimation of the produced Fe+2 with 1,10-phenanthroline. The absorbance of the tris(1,10-phenanthroline) Fe+2 complex was measured at 510 nm. Reaction conditions were optimized to obtain colored complex of higher sensitivity and longer stability. The absorbance concentration plots were rectilinear over the concentration rang of 5-90 and 1-20 μg/mL with lower detection limits of 0.74 and 0.01 μg/mL and quantification limits of 2.26 and 0.02 μg/mL for LBT and LER, respectively. The developed method was successfully applied for the determination of LBT and LER in bulk drugs and dosage forms. The common excipients and additives did not interfere in their determinations. There was no significant difference between the results obtained by the proposed and the reference methods regarding Student t-test and the variance ratio F-test.

Simultaneous Determination of Labetalol and Furosemide by First-Derivative Synchronous Spectrofluorimetry

A rapid, simple and highly sensitive first derivative synchronous spectrofluorimetric method was developed for the simultaneous analysis of a binary mixture of labetalol HCl (LBT) and furosemide (FUR) without prior separation. The method was based upon measuring the first derivative of synchronous fluorescence spectra of the two drugs at Deltalambda = 130 nm in aqueous ethanol (55% V/V). The different experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully studied and optimized. The first derivative amplitude-concentration plots were rectilinear over the range of 0.10 to 1.00 microg/mL and 0.05-0.50 microg/mL with lower detection limits of 0.0149 and 7 x 10(-3) microg/mL and quantification limits of 0.045 and 0.021 microg/mL for LBT and FUR, respectively. The proposed method was successfully applied for the determination of the studied drugs in synthetic mixtures. The results obtained were in good agreement with those obtained by the reference methods.

Drug–Organic Electrolyte Complexes as Controlled Release Systems

A water-insoluble complex between diltiazem HCl and Na deoxycholate was prepared to achieve sustained release dosage forms. Physicochemical characterization of the drug complex was carried out with differential scanning calorimetry, 1H-nuclear magnetic resonance, and Fourier transform infrared spectroscopy. These techniques showed that the characteristic peaks in both the drug and the complexing agent (protonated amine and carboxylate) disappeared and new peaks appeared upon formation of the ionic complex. The release of diltiazem from drug-complex tablets was sustained for a long period of time (>24 h) and was dependent on the pH of the dissolution medium. However, the dependence of drug release on pH was eliminated at pH 6–8 and minimized at pH 1.5 when drug-complex powders were incorporated in hydroxypropylmethylcellulose (HPMC) drug carriers. Unlike the release of diltiazem HCl from HPMC drug carriers, drug release from drug-complex/HPMC tablets was linear or near linear irrespective of the viscosity grade of the polymer (E15 to K4M). This is due to a shift in the controlling mechanism of drug release from drug diffusion to erosion of polymer. Also, drug release kinetics was not significantly affected by the water solubility of cationic drugs (diltiazem HCl, verapamil HCl, propranolol HCl, and labetalol HCl) ranging from 1.6 to 62% and the type of amine (i.e., secondary or tertiary). The same release characteristics were observed from the complexes between anionic drugs (Na salicylate, naproxen Na, and tolmetin Na) and benzathine diacetate as found from the complexes between cationic drugs and Na deoxycholate.

Rhinoplastic techniques for the nasal valve for the patient with sleep apnea

Treatment of nasal blockage is necessary to facilitate therapy of obstructive sleep apnea and improve continuous positive airway pressure tolerance. The importance of the nasal valve in controlling inspiratory airflow has been well documented. Defining the nasal valve region and correlating physiology with its anatomic and surgical findings can be confusing. Reliable interpretation of the different types of nasal valve dysfunction can be correlated with effective surgical repair to reduce nasal airway resistance. A simplified approach to standardizing surgical treatment of nasal valve problems is presented.

Controlled release from triple layer, donut-shaped tablets with enteric polymers

The purpose of this research was to evaluate triple layer, donut-shaped tablets (TLDSTs) for extended release dosage forms. TLDSTs were prepared by layering 3 powders sequentially after pressing them with a punch. The core tablet consisted of enteric polymers, mainly hydroxypropyl methylcellulose acetate succinate, and the bottom and top layers were made of a water-insoluble polymer, ethyl cellulose. Drug release kinetics were dependent on the pH of the dissolution medium and the drug properties, such as solubility, salt forms of weak acid and weak base drugs, and drug loading. At a 10% drug loading level, all drugs, regardless of their type or solubility, yielded the same release profiles within an acceptable level of experimental error. As drug loading increased from 10% to 30%, the drug release rate of neutral drugs increased for all except sulfathiazole, which retained the same kinetics as at 10% loading. HCl salts of weak base drugs had much slower release rates than did those of neutral drugs (eg, theophylline) as drug loading increased. The release of labetalol HCl retarded as drug loading increased from 10% to 30%. On the other hand, Na salts of weak acid drugs had much higher release rates than did those of neutral drugs (eg, theophylline). Drug release kinetics were governed by the ionization/erosion process with slight drug diffusion, observing no perfect straight line. A mathematical expression for drug release kinetics (erosion-controlled system) of TLDSTs is presented. In summary, a TLDST is a good design to obtain zero-order or nearly zero-order release kinetics for a wide range of drug solubilities.

Taste effects of lingual application of cardiovascular medications

Medications used to treat cardiovascular diseases such as congestive heart failure, high blood pressure, and arrhythmia, are prescribed extensively in Western countries. However, taste complaints are common side effects of many of these cardiovascular medications. Although clinical observations are helpful in determining potential taste problems from a medication, experimental studies are necessary to obtain quantitative data on taste. In the studies performed here, nine cardiovascular medications (labetalol HCl, captopril, diltiazem HCl, enalapril maleate, hydrochlorothiazide, propranolol HCl, mexiletine HCl, procainamide HCl, and propafenone HCl) were applied to the tongue in human volunteers to measure the direct effect of these drugs on taste receptors. The medications were applied topically to the tongue surface of both young and elderly subjects to mimic the situation in which the drug is secreted into the saliva. Detection thresholds ranged from 0.048 mM (propafenone) to 0.438 mM (procainamide). The detection thresholds of healthy elderly subjects did not significantly differ from young controls. The compounds tested had a predominantly bitter taste with other qualities as well. In addition, topical application of the medications to the tongue affected the taste of one or more taste stimuli, with medications differing in the pattern of taste effects exhibited. The mechanism of taste effects is not fully known, but the results of this study suggest one route may be due to medications' effect on peripheral taste receptors.

Enhanced and Retarded Drug Release from Hydrophobic Ionic Beads

Abstract The effect of drug solubility and drug loading on the kinetics of polymer ionization and drug release from poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been investigated. Acebutalol HCl, labetalol HCl, and propranolol HCl were chosen as model drugs, representing a range of liphophilicity. Polymer ionization and drug release rates increase with drug loading for a highly water-soluble drug, i.e., acebutalol HCl. Drug release and ionization rates, however, decrease with drug loading up to 11.0 and 12.2% for less water-soluble drugs, i.e., labetalol HCl and propranolol HCl, respectively, and then increase above the loading level of 18.6%. This decrease in rate is attributable to the low solubility of the drug, resulting in its slow diffusion and the need for increased electrolyte uptake to ionize the acidic components (i.e., polymer matrix and HCl). At a loading level below 18.6%, the ionization kinetics were governed by intraparticle diffusion and chemical reaction resistances, with an additional minor contribution from film diffusion resistance. At higher loading, above 24.6% of acebutalol HCl, however, the film diffusion resistance controlled the overall ionization kinetics of drug-loaded PMMA/MAA beads.