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

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

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 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.     

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

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.     

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

Abstract

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.     

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.     

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.     

The preparation of prolonged action formulations in the form of semi solid matrix into hard gelatin capsules of oxprenolol I. Thermocap method

Abstract

The aim of this study was to obtain prolonged action by preparing semi-solid matrices (SSM) into hard gelatin capsules using Oxprenolol as a model drug.

SSM formulations were prepared by using different lipophilic and hydrophilic pharmaceutical excipients, polyethylene glycols as channeling agent in the semi solid mass and Gelucires. The release kinetic of drug from these formulations was determined and compared with the commercial preparation in the form of polymeric matrix of this drug.

Among the generally used excipients, we have found that Gelucires were the most appropriate excipients for preparation of SSMs and drug release from these dosage forms can be improved by the method mentioned above depending on quantity and type of channeling agent which was used.     

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.     

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

Abstract

A stability-indicating high-performance liquid chromatography method for the quantitation of famotidine in injections, suspensions and tablets has been developed. The method is precise and accurate with a percent relative standard deviation of 1.1–1.3 based on 5 readings. The excipients present in the dosage forms did not interfere with the assay procedure. The recovery from the synthetic mixtures was quantitative. The samples decomposed under drastic conditions showed a total of 3 new peaks in the chromatograms     

Stability of Omeprazole Solutions at Various ph Values as Determined by High-Performance Liquid Chromatography

Abstract

A stability-indicating HPLC assay method for the quantitation of omeprazole has been developed. The developed method was used to study the effect of pH on the stability of omeprazole and to quantify the drug in capsules. The excipients present in the capsules did not interfere with the assay procedure. The pH-rate profile curve indicated that the maximum stability was at pH 11. Below pH 7.8, the decomposition was very fast. The decomposition constants have a direct relationship with the H+ concentrations of the solutions.     

Process and dosage form controlts: Formulation factors

Abstract

During the last decades, there have been considerable developments in the field of pharmaceutics, pharmaceutical technology and product manufacture.

The trend of the pharmaceutical industry is, like in most of the sophisticated industries, to produce, day after day, a better product, and as final goal, to manufacture continueously a perfect drug dosage form.

A few years ago, the defaults were counted in “percent”. After that, it was in per “thousand”. Now it is often expressed in “per million”, or even for very high series (for example empty hard gelatine capsules) the trend is “per billion”. Such an evaluation can only be achieved with a complete control of the whole manufacturing process.

The requirement for pharmaceutical dosage form are numerous (1): adequate biopharmaceutical profile, ease of manufacture, quality assurance (the dosage form must contain the correct quantity of the correct drug, and liberate it at the correct place, at the correct time, and in the correct quantity, with the correct speed), stability, …

These requirements can only be fulfilled with a perfect knowledge of the drug and the dosage form, from the beginning of the development of the dosage form (formulation) to the end of the manufacturing process (production and final product control).

It is the aim of the present lecture to show how important are the formulation factors and what is their influence on the processing and the dosage form control.     

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.     

High-Performance Liquid Chromatographic Determination of Ibuprofen in Bulk Drug and Tablets

Abstract

A simple and rapid HPLC procedure is described for the assay of ibuprofen in bulk drug and tablets and for dosage uniformity testing. HPLC was carried out on a stainless steel octadecylsilane (5 urn) column (150 × 4.6 mm) using 25% 0.25M glacial acetic acid in acetonitrile as the mobile phase, with UV detection at 254 nm. Results obtained with this procedure compared favorably with those obtained using the USP procedures.     

Validation of Liquid Chromatographic Method of Assay for Acetaminophen,Butalbital and Caffeine in Solid Dosage Forms

Abstract

The validation of a liquid chromatographic procedure for the determination of acetaminophen, butalbital and caffeine in solid dosage forms is described. The dosage content of tablets or capsules is diluted and chromatographed on a Radialpak Cyanopropylsilane Cartridge with a mobile phase of water-acetonitrile-1M dibutylamine phosphate (90+9+1, V/V) with detection at 215 nm. The calibration curve is linear with correlation coefficients of 0.999 for each component. Recoveries of spiked excipient blend averaged 99.5% for acetaminophen, 102.5% for butalbital and 101.0% for caffeine. The method met USP requirements for system suitability with proper resolution between two adjacent peaks. The relative standard deviation (RSD) of peak response of each component (obtained by chromatographing six replicates of standard solution) is less than 2.0% and the tailing factor of each component is not greater than 1.5. The method can be used for composite, content uniformity and dissolution assay of acetaminophen, butalbital and caffeine in tablet and capsule formulations.     

Quality assurance in pharmaceutical powder processing: Current developments

Abstract

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.     

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.     

Assay Development in Stability Test Methods

Abstract

Stability-indicating analytical methods are developed to monitor the stability of pharmaceutical dosage forms during the investigational phase of drug development, and, once the drug is marketed, for the ongoing stability studies which must be conducted. The development of these methods for pharmaceutical dosage forms forms can be approached from several avenues. Methods can be developed which measure the amount of drug remaining, the amount of drug lost (or the appearance of degradation products), or both.

Traditionally, the analytical methods used to monitor the stability of dosage forms have involved a generally non-specific spectrophotometric or titrimetric procedure for the assay of the active coupled with thin layer chromatography for the estimation of impurities and degradation products. In the last five years, this approach has changed dramatically. Currently, the method of choice for the quantitation of the active and degradation products is rapidly becoming high performance liquid chromatography. This method has obvious advantages since it both separates and measures and it lends itself well to automation. The disadvantages are that, in the absence of automation, the technique can be time-consuming, it is by no means universal, and it is relatively expensive. Recent advances in column technology have reduced some separation times to seconds and, in the next few years, this technique may find even greater utility.

HPLC, however, is not the only way to go. Other chromatographic methods still find a place, particularly gas chromatography when the stability of the component of interest does not pose a problem and thin layer chromatography for the rapid determination of degradation products. Other methods may also be used, including electrometric, e.g., polarography, and spectrophotometric, e.g., fluorimetry or NMR. The choice of an appropriate method must depend on both a scientific and practical evaluation of the drug and its dosage form.

Once an analytical method is chosen, the most important aspect of the development of a stability-indicating procedure is method validation. Validation should include evaluation of the following parameters: specificity, linearity, precision, accuracy, sensitivity, and ruggedness.

There are many other aspects to stability that could also be considered, e.g., the stability of the bulk drug and physical and organoleptic changes in a dosage form. These should be part of a separate discussion. It very often happens that, during the course of product development, analytical methods evolve. As more is learned about the drug and its dosage form, methods can be refined and revised.