Quantitation of Cefaclor in Pharmaceutical Dosage Forms Using High Performance Liquid Chromatography

Abstract

A stability-indicating high-performance liquid chromatography for the quantitation of cefaclor in pharmaceutical dosage forms has been developed. The method is accurate and precise with a percent relative standard deviation of 1.2 based on 5 readings. A number of inactive ingredients present in the capsules and suspensions did not interfere with the assay procedure. The extraction procedure from the dosage forms is very simple. The recovery from the synthetic mixtures was quantitative. The capsules which had expired 3 years ago lost only 3% of the potency. The drug appears to be very sensitive to strong acids or bases since a 5 minute boiling caused 100% degradation of drug in both the solutions.     

Stability-Indicating HPLC Method for Betaxolol HCl and Its Pharmaceutical Dosage Forms

Abstract

The present work describes a specific, stability-indicating high-performance liquid chromatographic method for determination of betaxolol HCl and its pharmaceutical dosage forms. Betaxolol HCl was chromatographed on a microbondapak C18 column utilizing a simple mixture of methanol: acetonitrile:0.1% diethylamine (pH 3.0 adjusted using orthophosphoric acid). It was detected at 222 nm. The method is accurate and precise with a percent relative standard deviation of 0.11 based on 6 readings. A number of inactive ingredients present in the dosage forms (eye drop, tablet, gel) did not interfere in the assay procedure. The recovery from synthetic mixtures was quantitative. The extraction procedure from the dosage forms is very simple. The drug appears to be very sensitive to acids (such as sulfuric acid) since 100% of the drug decomposed on boiling for 5 min.     

Quantitation of Cephalexin in Pharmaceutical Dosage Forms Using High-Performance Liquid Chromatography

A high-performance liquid chromatography method has been developed to quantify cephalexin in pharmaceutical dosage forms, capsules, pediatric drops and suspensions. The method is accurate and precise with a percent relative standard deviation of 0.8 based on 6 readings. There is no interference from a variety of excipients present in the dosage forms. The procedure for the extraction of cephalexin from the dosage forms is very simple. The method is stability indicating since a sample decomposed using sodium hydroxide showed very little potency and new peaks in the chromatogram. In the powder form cephalexin appears to be very stable.     

Quantitation of Cephalexin in Pharmaceutical Dosage Forms Using High-Performance Liquid Chromatography

Abstract

A high-performance liquid chromatography method has been developed to quantify cephalexin in pharmaceutical dosage forms, capsules, pediatric drops and suspensions. The method is accurate and precise with a percent relative standard deviation of 0.8 based on 6 readings. There is no interference from a variety of excipients present in the dosage forms. The procedure for the extraction of cephalexin from the dosage forms is very simple. The method is stability indicating since a sample decomposed using sodium hydroxide showed very little potency and new peaks in the chromatogram. In the powder form cephalexin appears to be very stable.     

Quantitation of Cefadroxil in Pharmaceutical Dosage Forms Using High-Performance Liquid Chromatography

A high-performance liquid chromatography method for the quantitation of cefadroxil has been developed. The method has been applied to quantify cefadroxil in pharmaceutical dosage forms (capsules, suspensions and tablets) of 2 different manufacturers. A simple extraction procedure to extract cefadroxil from the dosage forms has been developed. The results were excellent with percent relative standard deviation of 1.2 based on 5 readings. A variety of inactive ingredients present in the dosage forms did not interfere with the assay procedure. After formulating, the suspensions were stable for longer periods at 5^o than recommended on the label.     

Quantitation of Nizatidine in Capsules Using High-Performance Liquid Chromatography

A stability-indicating high-performance liquid chromatography method for the quantitation of nizatidine in capsules has been developed. The method is accurate and precise with a percent relative standard deviation of 0.34 based on 6 readings. A number of inactive ingredients present in the capsules did not interfere in the assay procedure. The recovery from the synthetic mixtures was quantitative. The extraction procedure from the capsules is very simple. The drug appears to be very sensitive to bases (such as sodium hydroxide) since 100% of the drug decomposed on boiling for 35 minutes. The drug was very stable when boiled with sulfuric acid.     

Quantitation of 5-Flucytosine in capsules using high-pressure liquid chromatography

A stability-indicating reversed phase HPLC method for the quantitation of 5-flucytosine in capsules (the only dosage form available) has been developed. The method requires the use of a mobile phase without any counterion and the samples can be assayed at room temperature. The method is simple, reproducible, precise and accurate with percent relative standard deviation of 0.77 based on 6 readings. There was no interference from the excipients present in capsules and from fluorouracil (the major product of decomposition of 5-flucytosine). The recovery of 5-flucytosine from the synthetic mixtures was quantitative. A simple extraction procedure for 5-flucytosine from the capsules has been developed.     

Quantitation of fluoxetine hydrochloride in capsules using high-performance liquid chromatography

A stability-indicating high-performance liquid chromatographic method for the quantitation of fluoxetine hydrochloride in capsules (the only dosage form available) has been developed. The method is accurate and precise with a percent relative standard deviation of 1.04 based on 6 readings. An excellent separation of fluoxetine from methyltestosterone (the internal standard) was achieved, and sharp peaks were obtained by adding acetic acid to the mobile phase. The inactive ingredients present in the capsule powder did not interfere with the assay procedure. The recovery of fluoxetine from the synthetic mixtures was quantitative. The drug appears to be very stable in the acidic medium and highly susceptible to degradation in the basic medium.     

Quantitation of Sulfacetamide, Sulfadiazine, Sulfamerazine and Sulfame Thazine in Various Cominations Dsing High-Performance Liquid Chromatography

A reverse phase high-performance liquid chromatography method for the quantitation of sulfacetamide, sulfadiazine, sulfamerazine, and sulfamethazine in various combinations has been developed. The method is simple, accurate, precise and reproducible. The percent relative standard deviations based on 6 injections were 2.1, 0.6, 1.9, and 1.6 for sulfacetamide, sulfadiazine, sulfamerazine, and sulfamethazine, respectively. The ratio of peak heights (drug/internal standard) wer closely related (r value 0.99 or better) to concentrations (± 20% of the standard solution concentrations). The results of synthetic mixtures showed quantitative recovery and method was successfully applied to commercial dosage forms (tablets and suspension). Extraction of sulfa drugs from the dosage forms required a very simple procedure.     

Quantitation of Sulfacetamide,Sulfadiazine, Sulfamerazine and Sulfame Thazine in Various Cominations Dsing High-Performance Liquid Chromatography

Abstract

A reverse phase high-performance liquid chromatography method for the quantitation of sulfacetamide, sulfadiazine, sulfamerazine, and sulfamethazine in various combinations has been developed. The method is simple, accurate, precise and reproducible. The percent relative standard deviations based on 6 injections were 2.1, 0.6, 1.9, and 1.6 for sulfacetamide, sulfadiazine, sulfamerazine, and sulfamethazine, respectively. The ratio of peak heights (drug/internal standard) wer closely related (r value 0.99 or better) to concentrations (± 20% of the standard solution concentrations). The results of synthetic mixtures showed quantitative recovery and method was successfully applied to commercial dosage forms (tablets and suspension). Extraction of sulfa drugs from the dosage forms required a very simple procedure.     

Nuclear Magnetic Resonance Analysis of Phenytoin and Sodium Phenytoin in Solid Dosage Forms

A rapid and specific nuclear magnetic resonance (NMR) spectroscopic method was developed for determining phenytoin and its sodium salt in capsules and tablets. Acetamide was used as the internal standard and 0.5% sodium deuteroxide in deuterium oxide served as the NMR solvent. The concentration of drug per unit dose was calculated from the integration values for the resonance signals of phenytoin at about 7.40 ppm and of the internal standard at about 1.97 ppm. The average recovery value of phenytoin added to synthetic samples, in concentrations ranging from 84 to 122 mg, was 99.9 ± 0.2% (SD) with a coefficient of variation of 0.2%. The method using commercial products gave results comparable to those obtained by the titrimetric and gravimetric methods of USP XX. Excipients of tablets and capsules such as sucrose and lactose did not interfere with the determinations. The proposed method was found suitable for measuring the content uniformity of capsules and tablets, and offered a positive means of identification on phenytoin in these dosage forms.     

Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study

The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank’s solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank’s solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.     

Quantitation of Propranolol Hydrochloride in Pharmaceutical Dosage Forms by High-Performance Liquid Chromatography

Abstract

A high-performance liquid-chromatography method for the quantitation of propranolol hydrochloride in pharmaceutical dosage forms (capsules, injections and tablets) has been developed. The method can also be used for contents uniformity as required by USP-NF. There is no interference from the excipients present and from hydrochlorothiazide which is often mixed with propranolol hydrochloride. The method is accurate, reproducible and precise with a percent relative standard deviation of 0.6 based on 5 readings. A sample decomposed with sodium hydroxide treatment showed about 9% potency and 2 new peaks in the chromatogram.     

Determinaion of Hard Gelatin Capsule Brittlenss Using a Motorized Compression Test Stand

Hard gelatin capsules are solid dosage forms containing powders, granulations, or pellets enclosed in a hard soluble shell. Recent guidelines for submitting documentation for the stability of human drugs and biologics to the FDA have requested test data for capsule brittleness. A simple test has been developed using a compression gauge to quantify the force required to fracture and/or shatter hard gelatin capsules. The data generated from this test can be utilized for dosage form stability assessment as well as quality control and quality assurance of capsules prior to their use in dosage from manufacture.     

Quantitation of Acyclovir in Pharmaceutical Dosage forms using High-Performance Liquid Chromatography

A stability-indicating high performance liquid chromatography method for the quantitation of acyclovir in pharmaceutical dosage forms (capsules, ointment and injection) has been developed. The method is accurate and precise with a percent relative standard deviation of 1.2 based on 5 readings. The excipients present in the dosage forms did not interfere with the assay method. The recovery from the synthetic mixtures was quantitative. The samples decomposed under drastic conditions showed a new peak in the chromatogram. Acyclovir appears to be more stable in the alkaline than in the acidic solution. There appears to be a distribution/decomposition problem with the ointment sample being marketed in certain types of tubes used previously and still on the market.     

Correlation of Dissolution-Dialysis Rates with Bioavailability of Nitrofurantoin Solid Dosage Forms

The correlation of in-vitro dissolution-dialysis rates of solid dosage forms with in-vivo bioavailability was investigated. Dissolution-dialysis measurements were made of 50mg and 100mg tablets and capsules of Nitrofurantoin commercial products. The samples used represented product lots whose bioavailability had been previously reported. The dissolution-dialysis medium used was pH 7.2 phosphate buffer. A cellulose dialysis membrane was used. A high degree of correlation was osbserved between apparent dialytic rate constant (K_app) of the drug and reported in-vivo bioavailability parameters for all 50mg tablets. But the 50mg capsule K_app value, measured under the same test conditions, was higher and did not correlate with the tablet data. However a value correlating with tablet data was obtained when the stirring speed was reduced from 100 RPM to 10 RPM. A satisfactory correlation was not obtained for the 100 mg dosage forms. This might be due to bladder drug saturation reported to occur at higher dose levels of Nitrofurantoin.     

Determinaion of Hard Gelatin Capsule Brittlenss Using a Motorized Compression Test Stand

Abstract

Hard gelatin capsules are solid dosage forms containing powders, granulations, or pellets enclosed in a hard soluble shell. Recent guidelines for submitting documentation for the stability of human drugs and biologics to the FDA have requested test data for capsule brittleness. A simple test has been developed using a compression gauge to quantify the force required to fracture and/or shatter hard gelatin capsules. The data generated from this test can be utilized for dosage form stability assessment as well as quality control and quality assurance of capsules prior to their use in dosage from manufacture.     

Quality assurance in pharmaceutical powder processing: Current developments

Pharmacopoeia1 requirements relating to standardization of the physical performance of oral dosage forms containing powders are usually limited to tests on the final product.

Such tests are aimed at ensuring that all tablets or capsules have the correct, nominal, drug content and that the drug is released into solution within a specified time. Whilst dissolution or disintegration test to assess drug release can only be carried out on a finished dosage form, content uniformity tests currently carried out on tablets or capsules alone could also be usefully carried out earlier on component powders at different stages during processing. The aim of developing a quality assurance procedure for quantifying the homogeneity of powders prior to tablet compaction or encapsulation would be to pin-point more precisely the part of a process where content uniformity problems arise. Secondly, a good quality assurance procedure would provide full mechanistic information about the behaviour of a given powder system, so that appropriate remedies could be applied.

Eleven different methods of testing homogeneity of powder mixes have been cited in pharmaceutically oriented literature and these will be reviewed in terms of their usefulness as routine quality assurance procedures for drug content uniformity. Of these 11 methods, 2 test methods were considered to be especially useful: one based on a flow test and the other on vibration analysis. This techniques has been validated using a complete vibration analysis and testing rig under conditions encountered during routine powder processing.

It would be desirable to see standard powder mixes tested on apparatus of the same design in different laboratories as a means of assessing the reproducibility of the proposed quality assurance method when used by different personnel.     

Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies

Background: Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. Method: The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE®, aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40°C/75% relative humidity] for 3 months. Results: All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Conclusions: Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.     

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.