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.     

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

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

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

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

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 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 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 Mathematical Model for Disintegration of Solid Dosage Forms Using a Cascading Disintegration Apparatus

Abstract

A modification in basket-rack assembly is proposed that enables one to develop the mathematical model for disintegration of solid dosage form. Once the parameters of the model is known, the true disintegration rate constant can be determined. The method is based on the assumption of deaggregation of solid dosage forms in a cascading system     

Comparative Evaluation of Four Dissolution Apparatus

Abstract

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.     

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.     

A Partially Organic Dissolution Medium for Griseofulvin Dosage Forms

Abstract

Forty percent alcohol in simulated gastric fluid was used as a dissolution medium for two griseofulvin dosage forms. Rank-order correlation of dissolution profiles with plasma levels was obtained.

The use of this partially organic dissolution medium for griseofulvin dosage forms is suggested as a convenient alternative to entirely aqueous media employed in large volumes (18 to 72 liters per dosage form).     

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     

Nasal Administration: A Tool for Tomorrow's Systemic Administration of Drugs

Abstract

By its anatomy and physiology, due to the great amount of air treated there, the nasal route represents a very interesting possibility for the administration of products degraded in the gastro-intestinal tract or inhibited by the first hepatic pass. The nasal dosage forms most studied are bioadhesive hydrogels and microspheres, especially for the systemic administration of peptides.     

Formulation of a Foaming Vaginal Tablet and Suppository

Abstract

Formulations for a foaming, spermicidal vaginal tablet and a foaming, spermicidal suppository are presented. Some pharmaceutical characteristics peculiar to both dosage forms were measured. A simple method is suggested for the evaluation of the quantity and collapse resistance of the foam.     

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.     

Carbamazepine Modified Release Dosage Forms

Abstract

The preparation of sustained release dosage forms of Carbamazepine (anti-epileptic drug characterized by a very low water solubility and by a short half life on chronique dosing) was carried out.

These formulations were obtained in two different steps:

a) modified release granules were prepared by the loading of cross-linked sodium carboxymethylcellulose (swellable polymer), with the drug and an enteric polymer. Cellulose acetate phthalate, methacrylic acid – methacrylic acid methyl ester copolymer (usually employed as enteric coating agents) and cellulose acetate trimellitate (a new enteric polymer) were used in different weight ratios.

b) some sustained release dosage forms were prepared tabletting physical mixtures of the modified release granules with different weight ratios of hydroxypropylmethylcellulose.

In vitro dissolution tests of modified release granules in gastric fluid (USP XXI) showed a modulation of the drug release, while in intestinal fluid (USP XXI) a quick drug dissolution was observed.

In vitro dissolution tests of sustained release dosage forms, performed varying during the test, the pH of the dissolution medium, (hydrochloric acid pH 1 from 0 to 2 hours and phosphate buffer pH 6.8 from 2 to 18 hours) showed that the determining factors in the controlling release of the drug are: the type and amount of enteric polymer constituting the granules and the amount of hydroxy-propylmethylcellulose mixed with them.     

Differential Scanning Calorimetry of Cephalexin-Dextrose and Cephalexin-Aspartame Mixtures

Abstract

The possible interaction of cephalexin with anhydrous dextrose and with aspartame, in the solid state, was investigaged by comparing the thermal behavior of physical mixtures of the respective original components in different molar ratios, using differential scanning calorimetry. Both anhydrous dextrose and aspartame were found to form complexes with cephalexin. The stoichiometries of these complexes were found to be 1:1 molar complexes between cephalexin and anhydrous dextrose and 4:1 and 1:1 molar complexes between cephalexin and aspartame. Complexed cephalexin was found to decompose at markedly lower temperatures than uncomplexed cephalexin.     

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.     

Soft Gelatin Capsijle Update

Abstract

The soft gelatin capsule is a relative unknown when compared to more traditional dosage forms. The technology and equipment. needed to prepare the gelatin mass and that. needed to encapsulate the fill material are highly specialized and not readily available. The acquisition of this equipment and technology is not usually economically feasible. The manufacture of soft gelatin capsules has. therefore, developed into primarily a contract manufacturing activity

Because of this. very little is known outside the encapsulation industry of the methods of production, advantages. Limitations, and other attributes of the soft elastic capsule This presentation explains the manufacturing process in order to give an understanding of current topics. Versatility of application. accuracy of dosage. content uniformity product. identification patient, compliance and other. attributes are discused. Consideration is also given to enhanced bioavailability, sustained release. and other innovations utilizing this unique dosage form