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 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 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.     

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 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 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.     

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.     

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.     

Production of an Extremly Low Dose Procaterol HCl Preparation by Fluidized-Bed Coating Method: In Vitro and In Vivo Evaluation

Abstract

A convenient and reliable method to prepare procaterol HCl oral dosage form at an extremely low dosage (25 µg/cap) is presented in this paper. Procaterol HCl was mixed with the film-forming agent hydroxypropyl methylcellulose in an aqueous solution, which was then spray-coated on sugar spheres (Nu-pareil PG 20/25) to produce procaterol HCl pellets. The IR spectra of coated and noncoated pellets indicated that procaterol HCl was coated on the sugar spheres successfully with a weight increment less than 1%. Most of the coated pellets were able to pass through an 18-mesh screen with no agglomeration. The average weights of coated pellets filled inside of capsules were monitored during the filling process. A simple liquid chromatographic method was developed and validated for the assay and uniformity test of procaterol HCl in different dosage forms. The results of assay and content uniformity test for both in-house product and a commercial product, i.e., Meptin®-mini tablet, were satisfied. The data of f₂ function and ANOVA analysis for the dissolution profiles of both procaterol HCl products suggested that they are pharmaceutical equivalent.

In an in vivo study (n = 24), a single dose of 75 µg procaterol HCl was administrated to each volunteer and the plasma concentration of procaterol was determined by a LC/MS/MS method, developed by the same authors. There were no significant differences (p > 0.05) in the data of AUC_0→16h, AUC_0→∞, C_max, and MRT for both preparations. It is confirmed that the pellets capsule produced in this study is bioequivalent with Meptin®-mini tablet.     

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.     

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.     

Determination of rifampicin and isoniazid in pharmaceutical formulations by HPLC

Abstract

A liquid chromatographic procedure for the analysis of Rifampicin (RIF) and Isoniazid (INH) in pharmaceutical dosage forms utilizing reverse phase chromatography was developed. Isolation of analytes was carried out under isocratic conditions with a octadecylsilane column and an aqueous mobile phase containing Methanol (75%) and 0.02 M Disodium Hydrogen Orthophosphate (25%) with pH 4.5 adjusted with orthophosphoric acid. The detection was done at 254 nm.

The method is unique in analysing Rifampicin precisely in combination with Isoniazid particularly in liquid formulation. The method is specific and can distinctly isolate the degradation product in suspension.     

Rapid and sensitive estimation of isoniazid,pyrazinamide and rifampicin in combined dosage form by reversed-phase liquid chromatography

Abstract

A rapid and sensitive method of estimation for isoniazid, pyrazinamide and rifampicin from pharmaceutical dosage was developed. The mobile phase consisting of 80:20, methanol-tetrabutyl ammonium hydroxide (0.005N) pH 3.0 adjusted with phosphoric acid was used with an ODS -CN bonded phase column. The separation of the above drugs was accomplished within 10 min at a flow rate of 1.5 ml/min. For accurate quantitation clofazimine was used as an internal standard with UV detector set at 265 nm. No interference from a variety of excipients present in the dosage forms was observed.     

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 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     

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.     

Determination of the Nasal Decongestant,Oxymetazoline Hydrochloride,in Pharmaceutical Formulations by Hplc

Abstract

A liquid chromatographic procedure for the analysis of oxymetazoline hydrochloride in pharmaceuticals utilizing reversedphase ion-pairing was developed. Isolation of the analyte was carried out under isocratic conditions with a octadecylsilane column and an aqueous mobile phase containing methanol (70%), acetic acid (1%) and 0.005M sodium pentanesulfonate with detection at 280 νm. The procedure was applied to a drug product quality survey including the bulk drug substance and twenty-one nasal decongestant formulations. The overall precision (CV) for the liquid product assays ranged from 0.11 to 2.02% and recovery values based on sample fortification ranged from 97.5 to 100.5%. The procedure is simple to perform and specific with respect to common formulation excipients.     

Development of electrosprayed artesunate-loaded core–shell nanoparticles

Objective: Artesunate (ART) is proven to have potential anti-proliferative activities, but its instability and poor aqueous solubility limit its application as an anti-cancer drug. The present study was undertaken to develop coaxial electrospraying as a novel technique for fabricating nanoscale drug delivery systems of ART as the core–shell nanostructures.

Methods: The core–shell nanoparticles (NPs) were fabricated with coaxial electrospraying and the formation mechanisms of NPs were examined. The physical solid state and drug–polymer interactions of NPs were characterized by X-ray powder diffraction (XRPD) and Fourier transform infrared (FTIR) spectroscopy. The effects of materials and electrospraying process on the particle size and surface morphology of NPs were investigated by scanning electron microscopy (SEM). The drug release from NPs was determined in vitro by a dialysis method.

Results: The ART/poly(lactic-co-glycolic) acid (PLGA) chitosan (CS) NPs exhibited the mean particle size of 303?±?93?nm and relatively high entrapment efficiency (80.5%). The release pattern showed an initial rapid release within two hours followed by very slow extended release. The release pattern approached the Korsmeyer–Peppas model.

Conclusions: The present results suggest that the core–shell NPs containing PLGA and CS have a potential as carriers in the anticancer drug therapy of ART.     

Studies on Controlled Release Formulations of Pentazocine Hydrochloride

Abstract

This work embodies studies, performed with micropellet type dosage forms of Pentazocine Hydrochloride (Pz-HCl), using single and composite matrices of Eudragit RS100 (RS) and RL100 (RL). The effects of formulation parameters on various dosage form criteria - namely drug loading, particle size distribution, release profiles etc. have been investigated. Results indicate, that the two polymers can be successfully combined to produce different changes in release kinetics, with simple modifications of coating composition and initial drug loads.