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.     

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 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.     

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.     

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.     

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

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 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 Promethazine Hydrochloride in Pharmaceutical Dosage Forms Using High Performance Liquid Chromatography

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.     

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 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.     

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.     

Assay Development in Stability Test Methods

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.     

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.     

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.     

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.     

A review on the taste masking of bitter APIs: hot-melt extrusion (HME) evaluation

The majority of active pharmaceutical ingredients (APIs) found in oral dosage forms have a bitter taste. Masking the unpleasant taste of bitter, APIs is a major challenge in the development of such oral dosage forms. Taste assessment is an important quality-control parameter for evaluating taste-masked formulations of any new molecular entity. Hot-melt extrusion (HME) techniques, have very recently, been accepted from an industrial compliance viewpoint in relation to both manufacturing operations and development of pharmaceuticals. HME achieves taste masking of bitter APIs via various mechanisms such as the formation of solid dispersions and inter-molecular interactions and this has led to its wide-spread use in pharmaceutical formulation research. In this article, the uses of various taste evaluation methods and HME as continuous processing techniques for taste masking of bitter APIs used for the oral delivery of drugs are reviewed.     

Development of An Oral Sustained-Release Antibiotic Matrix Tablet Using In-Vitro/In-Vivo Correlations

A sustained release (SR) cephalexin tablet formulation containing xanthan gum and sodium alginate as matrix formers was evaluated in human volunteers. The formulation was optimized based on response surface analysis and computer simulation of cephalexin plasma levels versus time curves. The optimized formulation was tested in-vivo in human volunteers along with a fast release (FR) capsule formulation. The SR matrix formulation prolonged the cephalexin blood levels up to 8 hours in humans. The matrix formulation reduced variations in cephalexin plasma levels in individual subjects without any dose dumping as compared to the FR formulation. The plasma levels predicted by the computer program using in-vitro release data and the drug's pharmacokinetic parameters showed excellent correlation with in-vivo data. Using the Wagner-Nelson method, there was good correlation between in-vitro dissolution and in-vivo absorption in individual subjects. The relative bioavailability of cephalexin was reduced by about thirty percent. Very little absorption was seen after six to eight hours. The SR matrix formulation is an alternative delivery method to produce prolonged concentrations.     

Comparative Evaluation of Four Dissolution Apparatus

Four dissolution methods, the rotating basket, the rotating paddle, the rotating basket with paddle and the stationary basket-rotating paddle, were evaluated using capsules and non-disintegrating pellets of salicylic acid. The agitation intensity produced by the rotating basket method was very low and differed significantly throughout the vessel. However, it did not differ significantly at different positions in the stationary basket-rotating paddle method. This method offered considerable advantages and hence appears to be a suitable alternative to the existing compendial methods which have limitations for evaluation of dosage forms which tend to float on the dissolution medium.     

Determination of azathioprine and its related substances by capillary zone electrophoresis and its application to pharmaceutical dosage forms assay

The development of a stability-indicating capillary zone electrophoresis (CZE) method for the determination of the drug azathioprine (AZA) and its related substances in bulk and dosage forms is described. Theophylline was used as an internal standard to improve quantitative results. The method was fully validated in terms of repeatability (n = 10, RSD for migration time and peak area ratio were 0.15% and 0.60%, respectively), reproducibility (n = 5, RSD of peak area ratio was 0.84%), linearity at two ranges of the azathioprine concentration, limits of detection (LOD) and quantitation (LOQ), and robustness. The method was applied for determination of the drug in bulk and a commercial tablet dosage form (recovery 98.3-101.3%) and in powder for injection (recovery 98.7-100.6%). The method was fast and reliable for the analysis of AZA and its related substances in bulk and dosage forms.