Propranolol Hydrochloride Binding in Calcium Alginate Beads

Abstract

The interaction of propranolol hydrochloride with alginate molecular chains in calcium alginate beads was investigated. The drug was either incorporated into formed calcium alginate gel beads or incorporated simultaneously with the gelation of alginate beads by Ca²⁺. Bed produced by the former method had a higher drug content and lower Ca²⁺ level compared to those prepared by the latter method. The extent of drug binding to the alginate molecules increased with decreasing Ca²⁺ levels in the beads, indicating that propranolol and Ca²⁺ shared common binding sites in the alginate chains, me appearance of the beads and the molphology of the alginate polymer in the beads were affected by the amounts of both propranolol and Ca²⁺ in the beads. Differential scanning calorimetry (DSC) analyses showed that the formation of the calcium alginate gel structure was impeded in the presence of propranolol molecules.     

An In Vitro Evaluation of Fenugreek Mucilage as a Potential Excipient for Oral Controlled-Release Matrix Tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46–0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

In Vitro Adsorption of Propranolol Hydrochloride by Various Antacids

The purpose of this study was to investigate by in vitro methods whether an interaction takes place between propranolol hydro-chloride and adsorbents when antacids are taken concomitantly with the beta-blocker or when excipients having adsorbent properties are present in formulations of the drug products containing propranolol hydrochloride.

Specific surface areas of magnesium trisilicate, magnesium oxide, magnesium hydroxide, dihydroxy aluminum sodium carbonate, magnesium carbonate and kaolin were calculated from nitrogen adsorption isotherm using single pint method and it was found. that magnesium trisilicate has the largest specific surface area.

The adsorption of propranolol hydrochloride to these adsorbents was investigated by in vitro methods. The adsorption isotherms were drawn and the adsorptive capacities of the adsorbents were calculated from the slopes. It was found that magnesium tri-silicate, magnesium hydroxide arid dihydroxy aluminum sodium carbonate possess the highest adsorptive capacities while kaolin and magnesium carbonate possess the lowest.

The results of the adsorption studies indicate that the concomitant use of propranolol hydrochloride and the above mentioned adsorbents could affect the bioavailability of the beta-blocker adversely.     

Gas Liquid Chromatographic Determination of Promethazine Hydrochloride in Cocoa Butter-White Wax Suppositories

Abstract

A gas liquid chromatographic method is described for the determination of promethazine hydrochloride in cocoa butter-white wax suppositories. This assay method is capable of distinguishing promethazine hydrochloride from its thermal and photolytic degradation products. Promethazine and promazine were eluted in 15 minutes with retention times of 8.6 and 10.1 minutes respectively. A linear relationship between peak height ratio (promethazine/promazine) and promethazine hydrochloride concentration was found up to 600 μg/ml. The coefficient of variation of the assay method over several days were found to be 2.07%. Finally, the recovery of promethazine ranged from 72 - 76% in the presence and absence of cocoa butterwhite wax vehicles.     

Release and permeation studies of propranolol hydrochloride from hydrophilic polymeric matrices

Abstract

In-vitro release of propranolol hydrochloride, from various hydrophilic polymeric bases was studied. These included: methocel®, avicel® CL-611/ methylcellulose, polyvinyl alcohol/gelatin based systems. Several additives, such as, ethyl alcohol, dimethylsulfoxide (DMSO) and polyethylene glycol-400 were included in the formulations for possible enhancement of the drug release. The release studies were carried out using the cellulose membrane and the hairless mouse skin as the diffusion barriers. The general rank order for the drug release through these membranes was observed to be: the methocel® matrix > the avicel® CL-611 matrix > the polyvinyl alcohol/gelatin matrix > and the emulsion base. The additives in the formulations had little or no effect in enhancing the drug release. However, when the hairless mouse skin was soaked in (DMSO) for one hour prior to its use in the diffusion studies, the drug release was found to increase by 40% from the methocel® matrix formulation.

The drug release data were treated with various kinetic principles to assess the relevant parameters, such as the diffusion, partition and permeability coefficients. Using these information, the formulations were screened for their suitability to deliver propranolol hydrochloride via the diadermatic dosage form.     

A Simplified Rat Model for Studying Nasal Drug Absorption

Abstract

A simple and rapid rat model for studying nasal drug absorption was developed. In this model, a solution of the test drug, propranolol hydrochloride, was gradually deposited into the nasal cavity of an anesthetized rat through a PE-20 polyethylene catheter connected to a tuberculin syringe via a 30 gauge needle. The extent of drug bioavailability was assessed by measuring propranolol blood levels and the changes in heart rate. For comparative purposes, identical experiments were repeated using the intravenous route of administration, an established rat model requiring surgery, and the proposed model after tracheal cannulation and esophageal li-gation. Although the pharmacokinetic parameters for the various models tested indicated bioavailabilities that were quite similar to that obtained by the intravenous route of administration, the drop in heart rates appeared to be more pronounced with the proposed model than with any of the other two models. In addition to its simplicity, the proposed rat model represents a less stressful and more physiological means of delivering a drug by the nasal route.     

Effect of Particle Size on the Dissolution Characteristics of Chlorthalidone

Abstract

The particle size reduction of chlorthalidone by fluid energy milling, Alpine milling and Fitzpatrick milling were evaluated. The desired particle size was achieved by both the fluid energy milling and Alpine milling processes. Alpine mil1ing, however, is a more complex process and is susceptible to product decomposition, whereas fluid energy milling is a simple and efficient process without any risk of product decomposition. The desired particle size cannot be achieved by Fitzmilling because of the low probability of impaction force on particles. The dissolution rate of the chlorthalidone from chlorthalidone/propranolol hydrochloride tablets (25/80 mg) prepared with fluid energy milled chlorthalidone was significantly better than the tablets prepared with Fitzpatrick - milled chlorthalidone. The minimum effective specific surface area of chlorthalidone needed for maximum dissolution in water was found to be around 3.5 m²/g.     

Sustained-Release Dosage Form of Nicardipine Hydrochloride: Application of Factorial Design and Effect of Surfactant on Release Kinetics

Abstract

Microcapsules of nicardipine hydrochloride with core:wall ratios of 1:1, 2:1, and 1:2 were prepared by the coacervation-phase separation method, using ethyl-cellulose as the coating material. Two batches of nicardipine hydrochloride microscapsules were divided into size fraction by using standard sieves ranging from 840 μm to 476 pn. Dissolution rate studies from microcapsules were performed using the USP XXII basket method. The kinetic model according to the Rosin-Rammler-Sperling-Bennet-Weibull (RRSBW) distribution was applied for the parametric representation of the dissolution curves. Preparation and dissolution rate studies on the nicardipine hydrochloride microcapsules were pellformed and the influence of particle size, core:wall ratio, and the amount of nicardipine hydrochloride on the release rate was examined by 2³ factorial design. The sign@cance of the observed effects was tested with the F test. A surface active substance was added in the dissolution medium to understand how this substance effects the release of drug from ideal microcapsule form which is found by the findings of the 2³ factorial design. Dissolution studies were repeated with this ideal formulation using different ratio of Tween 20.

The results of this study suggested that the solubility and bioavailability of the sustained-release dosage forms of nicardipine hydrochloride using sullface active substances could be increased.     

Quantitation and Stability of Verapamil Hydrochloride using High-Performance Liquid Chromatography

Abstract

A high-performance liquid chromatography method for the quantitation of verapamil hydrochloride in pharmaceutical dosage forms has been developed. The method is precise and accurate with a relative standard deviation of 0.63% based on six injections. No preliminary extraction procedure is required to assay injections and a very simple extraction procedure is needed for tablets. There is no interference from the excipients and the method appears to be stability-indicating. The optimum pH range of stability is about 3.2 to 5.6 and the phosphate buffer and ionic strength have very little effect on the stability. Verapamil hydrochloride appears to be a very stable compound since in 105 days at 50°, the aqueous solutions (0.5 mg/ml) did not decompose.     

Pharmaceutical development of an amorphous solid dispersion formulation of elacridar hydrochloride for proof-of-concept clinical studies

Objective: A novel tablet formulation containing an amorphous solid dispersion (ASD) of elacridar hydrochloride was developed with the purpose to resolve the drug’s low solubility in water and to conduct proof-of-concept clinical studies.

Significance: Elacridar is highly demanded for proof-of-concept clinical trials that study the drug’s suitability to boost brain penetration and bioavailability of numerous anticancer agents. Previously, clinical trials with elacridar were performed with a tablet containing elacridar hydrochloride. However, this tablet formulation resulted in poor and unpredictable absorption which was caused by the low aqueous solubility of elacridar hydrochloride.

Methods: Twenty four different ASDs were produced and dissolution was compared to crystalline elacridar hydrochloride and a crystalline physical mixture. The formulation with highest dissolution was characterized for amorphicity. Subsequently, a tablet was developed and monitored for chemical/physical stability for 12 months at +15–25?°C, +2–8?°C and ?20?°C.

Results: The ASD powder was composed of freeze dried elacridar hydrochloride–povidone K30–sodium dodecyl sulfate (1:6:1, w/w/w), appeared fully amorphous and resulted in complete dissolution whereas crystalline elacridar hydrochloride resulted in only 1% dissolution. The ASD tablets contained 25?mg elacridar hydrochloride and were stable for at least 12 months at –20?°C.

Conclusions: The ASD tablet was considered feasible for proof-of-concept clinical studies and is now used as such.     

An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel^® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

Drug release from lipid liquid crystalline phases: relation with phase behavior

Introduction: We studied the release of propranolol hydrochloride (PHCl), a water-soluble amphiphilic drug, from monoolein (MO)/water and phytantriol/water systems. Methods: We related the dissolution profiles with phase behavior and viscosity of the different liquid crystalline phases. Diolein has been added aiming to stabilize the cubic phases and thus preventing formation of less viscous (lamellar) phases. Results: Formulations display first-order release rates and diffusion release mechanism. Some formulations (mostly MO) were close to zero-order release in the first 120 minutes. Discussion: Release mechanism can be influenced by phase changes during dissolution. Conclusions: Both MO and phytantriol show good potential to be used for propranolol hydrochloride sustained drug release.     

Determination of Hydralazine Hydrochloride and Hydrochlorothiazide in Dosage Forms by High Performance Liquid Chromatography

Abstract

A high performance liquid chr0matOgraphiC method is presented for the simultaneous determination of hydralazine hydrochloride and hydrochlorothiazide in combination dosage forms. ccmpounds are chromatographed on a radialpak cyanopropylsilane cartridge with a mixture of methanol, water and dibutylamine phosphate as mobile phase and W detection at 254 run. hydralazine hydrochloride and hydrochlorothiazide showed linear detector responses over a range of 50-150% of label claim with correlation coefficients of 0.999. Assay recoveries (n = 5) were found to contain an average of 98.9% hydrochloride and 98'.8% 2 1.1 of hydrochlorothiazide. proposed method showed excellent resolution and reproducibility. It will be helpful in routine quality control analysis of such combination dosage forms.     

Effect of Various Factors on the Corrosion and Rusting of Tooling Material Used for Tablet Manufacturing

Abstract

Various factors that cause the rusting of tablet punches and dies by a hydrochloride salt were evaluated. Tooling material rich in nickel content was found to have the best resistance to rusting by the hydrochloride salt. Other factors such as humidity, temperature and contact time with this hydrochloride salt were also found to be responsible for rusting of tooling material.

The hydrogen chloride liberated from the salt was found to be the cause of rusting of tooling. A correlation between the stability of hydrochloride salt as determined by thermogravimetric analysis and its effect on rusting of tooling material was demonstrated. Optimization of tooling composition during preformulation is recommended.     

Quantitation of Promethazine Hydrochloride in Pharmaceutical Dosage Forms Using High Performance Liquid Chromatography

Abstract

A stability-indicating HPLC assay method has been developed to quantify promethazine hydrochloride in pharmaceutical dosage forms, injection, oral liquids, suppositories and tablets. The method is accurate and precise with a percent relative standard deviation of 0.4 based on 6 readings. The recoveries from the synthetic mixtures were quantitative. Three new peaks in the chromatogram were detected from a decomposed sample. A number of active and inactive ingredients, colors, preservatives, flavors, antioxidants, phenylephrine and codeine present in the dosage forms did not interfere with the assay procedure.     

Evaluation of the percutaneous absorption of chlorpromazine from PLO gels across porcine ear and human abdominal skin

Objective: The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life.

Methods: PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (C_ss) of chlorpromazine was calculated from the flux values.

Results: The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical C_ss of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50?ng/ml, respectively. PLO gels only marginally increased the flux and theoretical C_ss of chlorpromazine.

Conclusion: From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.     

Dissolution Profiles of Long-Acting Quinacrine Hydrochloride Pellets II

Abstract

Quinacrine hydrochloride is a well known drug used safely as an antimalarial agent and also could be used for permanent non-surgical female sterilization. In the present investigation the dissolution studies of the long-acting quinacrine hydrochloride pellets were carried by U.S.P. basket method. And it is seen that the drug release is principally through leaching and drug diffusion from the matrix. The plot of drug dissolved against time in the semilogaritmic presentation showed that the release kinetics is of first order.     

Analysis of Metoclopramide and Related Compounds in Tablets by Liquid Chromatography

Abstract

A rapid, sensitive, stability indicating, reversed phase HPLC method for the quantitation of Metoclopramide and its related compounds is described. The sample is extracted in methanol and injected on a reverse phase CIS column with a mobile phase of 0.15M ammonium acetate and acetonitrile (80:20) with Wdetection at 268 nm. The method is highly specific, sensitive and has the ability to separate Metoclopramide from its related compunds; narnely, 4-acetylamino-5-chloro-N[2(diethylamino)ethyll-2-methoxybenzamide hydrochloride and 4-amino-5-chloro-2-methoxybenzoic acid in quantities of up to 10 ucg/mL. The method is highly reproducible with average assay recovery of 104.7 2 1.1%.     

Dsc Screening for Drug-Drug Interactions in Poly Pharmaceuticals Intended for the Alleviation of the Symptoms of Colds and Flu. II.

Abstract

DSC screening for drug-drug interactions of a polypharmaceutical capsule dosage form containing salicylaminde, ascorbic acid, pyrilamine maleate and phenylephrine hydrochloride was performed. The results show the following:

1. Ascorbic acid is incompatible with salicylamide, pyrilamine maleate and pheynylephrine hydrochloride.

2. Salicylamide is incompatible with ascorbic acid, pyrilamine maleate and phenylephrine hydrochloride.

3. Pyrilamine maleate is incompatible with ascorbic acid, salicylamide and phenylephrine hydrochloride.

4. Phenylephrine hydrochloride is incompatible with salicylamide, pyrilamine maleate and ascorbic acid.     

Quantitation of Ranitidine Hydrochloride in Tablets and Injections Using High-Performance Liquid Chromatography

Abstract

A stability-indicating reverse-phase high-performance liquid chromatography method without the use of a counterion has been developed to quantify ranitidine hydrochloride in pharmaceutical dosage forms. The method is accurate and precise with a percent relative standard deviation of 1.5 based on 5 injections. The extraction procedure for ranitidine from tablets is very simple and there was no interference from the excipients present. Ranitidine appears to be stable to heat on the acidic side and very susceptible to decomposition on the basic side. It lost 84.4% of potency on 20 minute boiling with sodium hydroxide with a new peak in the chromatogram. It lost 37.8% of the potency on treatment with hydrogen peroxide solution for 20 minutes at room temperature with 2 new peaks in the chromatogram.