An Isocrstic Reversed—Phase Separation and Determination of and Phenytoin in Tablets by High Performance Liquid Chromatogrphy

An isocratic, sensitive high-per-Formance liquid chromatographic method has been developed for the determination of phenobarbitone, methylphenobarbitone and phenytoin in tablets. A reversed-phase octadecylsilane column, 10 µ, was utilized with a mobile phase consisting of 45% methanol, 55% water and 0.5 ml glacial acetic acid at a flow rate of 1.8 ml/min. The samples were dissolved in methanol containing diethylbarbituric acid as an internal standard. Quantitation was achieved with UV detection at 240 nm and by the measurment of the peak area ratio.     

An Isocrstic Reversed—Phase Separation and Determination of and Phenytoin in Tablets by High Performance Liquid Chromatogrphy

Abstract

An isocratic, sensitive high-per-Formance liquid chromatographic method has been developed for the determination of phenobarbitone, methylphenobarbitone and phenytoin in tablets. A reversed-phase octadecylsilane column, 10 µ, was utilized with a mobile phase consisting of 45% methanol, 55% water and 0.5 ml glacial acetic acid at a flow rate of 1.8 ml/min. The samples were dissolved in methanol containing diethylbarbituric acid as an internal standard. Quantitation was achieved with UV detection at 240 nm and by the measurment of the peak area ratio.     

Semisolid matrix filled capsules: an approach to improve dissolution stability of phenytoin sodium formulation

Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30°C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.     

1H-NMR Spectroscopic Assay Method for Metoclopramide Hydrochloride in Tablets and Injections

A simple, accurate and specific proton nuclear magnetic resonance (¹H-NMR) spectroscopic method has been developed for the assay of metoclopramide hydrochloride in tablets and injections. In deuterium oxide, the analyte and acetamide, the internal standard, produced corresponding resonance signals at 1.35 ppm and 2.03 ppm of utility for quantitative purposes. The average ± SD recovery of drug from 10 synthetic formulations was 99.7 ± 0.7% of the added amount. The assay of commercial products by the proposed method resulted in average assay values of 100.43 (range = 98.8-100.8, n = 6)% of declared for tablets, and of 99.45 (range = 99.6-100.4, n = 4)% of declared for injections. These results were validated by a high performance liquid chromatographic (HPLC) method.     

1H-NMR Spectroscopic Assay Method for Metoclopramide Hydrochloride in Tablets and Injections

Abstract

A simple, accurate and specific proton nuclear magnetic resonance (¹H-NMR) spectroscopic method has been developed for the assay of metoclopramide hydrochloride in tablets and injections. In deuterium oxide, the analyte and acetamide, the internal standard, produced corresponding resonance signals at 1.35 ppm and 2.03 ppm of utility for quantitative purposes. The average ± SD recovery of drug from 10 synthetic formulations was 99.7 ± 0.7% of the added amount. The assay of commercial products by the proposed method resulted in average assay values of 100.43 (range = 98.8-100.8, n = 6)% of declared for tablets, and of 99.45 (range = 99.6-100.4, n = 4)% of declared for injections. These results were validated by a high performance liquid chromatographic (HPLC) method.     

Quantitation of Scopolamine Hydrobromide When Adsorbed Onto Microcrystalline Cellulose and Sodium Carboxymethylcellulose in Tablets

Abstract

Both scopolamine and lidocaine (the internal standard) got adsorbed onto sodium carboxymethylcellulose and microcrystalline cellulose, which are commonly added to the tablets/capsules as excipients. In one tablet formula which contained both adsorbents, about 42% of scopolamine and 45% of lidocaine got adsorbed. Sodium carboxymethylcellulose by itself, adsorbed both drugs about 26.2 times more than microcrystalline cellulose, when compared on the basis of same weights. If hydrochloric acid was used in the extraction procedure, both scopolamine and lidocaine got desorbed and recovery was quantitative.     

A study on in vitro release of five brands of phenytoin capsules,marketed in iran

Abstract

In relation to the new pharmaceutical system in Iran, the in vitro release of five brands of 100 mg phenytoin sodium capsules, namely A,B,C,D & E were determined in distilled water. using three dissolution methods, i.e. Rotating basket, Magnetic basket and Levy beaker method. Also the average amount of phenytoin content of each brand was measured.

The results showed that although the dissolution rate of each product is different by each method, but the pattern of drug release is more or less similar.

The dissolution time for products C and D is much longer than those of products A,B & C with all methods, but the dissolution behaviour of capsules C & D is not equivalent to those of standard “slow release” phenytoin capsules. The release pattern of products A & E are similar to those of standard “fast release” phenytoin capsules. The dissolution of product B is poor and not acceptable.     

A study on in vitro release of five brands of phenytoin capsules, marketed in iran

In relation to the new pharmaceutical system in Iran, the in vitro release of five brands of 100 mg phenytoin sodium capsules, namely A,B,C,D & E were determined in distilled water. using three dissolution methods, i.e. Rotating basket, Magnetic basket and Levy beaker method. Also the average amount of phenytoin content of each brand was measured.

The results showed that although the dissolution rate of each product is different by each method, but the pattern of drug release is more or less similar.

The dissolution time for products C and D is much longer than those of products A,B & C with all methods, but the dissolution behaviour of capsules C & D is not equivalent to those of standard “slow release” phenytoin capsules. The release pattern of products A & E are similar to those of standard “fast release” phenytoin capsules. The dissolution of product B is poor and not acceptable.     

Evaluation of Pharmaceutical Quality of Phenytoin Sodium Capsules and Tablets from Multinational Markets*

This report presents the results obtained in the above-titled study for the quality of phenytoin sodium tablets and capsules (100 mg) available in the markets of various countries worldwide, especially members of the Official Laboratories and Medicines Control Services (OLMCS) section of FIP. The products were analyzed following a common protocol based on the methodologies described in the European (Ph.Eur.), British (BP), and/or United States Pharmacopeia (USP). Pharmacotechnic tests (uniformity of weight, disintegration), identification, assay, and dissolution of active ingredient were preformed by 23 laboratories from 20 countries that submitted data from 52 samples representing 37 products available in the local markets. Innovator products from 17 countries were analyzed in LEF. Most products tested &Wed the pharmacopeial requirements concerning uniformity of weight, disintegration, identity, and content. Marked differences were recorded in respect of in vitro dissolution behavior. This applies not only to the products of different brands but also among lots of the same brand name produced in difei-ent countries     

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.     

Rectal Absorption of Phenytoin in Rabbits from Polyethylene Glycol Suppositories

Abstract

Various suppositories containing phenytoin and phenytoin sodium were formulated with different polyethylene glycol combinations. The three formulae that had the best in vitro release rate were administered to rabbits. Phenytoin was well absorbed from the suppositories, and the results show that rectal administration of phenytoin can be an alternative to oral administration.     

Preparation of Gelatin: Phenytoin Sodium Microsphers: An IN VITRO and IN VIVO Evaluation

In this study phenytoin sodium microspheres were formulated with biodegradable acid-treated gelatin. The microspheres were subjected to in vitro and in vivo testing. The percent drug retained in the microspheres, as well as its release from the microspheres, was tested. In vitro data revealed a decrease in percent druq retained in the microspheres with an increase in addition of glutaraldehyde to the microsphere formulations. The statistically most consistent drug release was observed from formulations containing 10 g of gelatin and 2 g of phenytoin sodium. From this formulation the slowest release was observed when 5 ml of glutaraldehyde were added to the various formulations, whereas the fastest release was observed when no glutaraldehyde was added. In vivo studies consisted of administering phenytoin sodium in microsphere form and an aqueous solution v i a various routes of administration and determining phenytoin plasma concentration vs. time profiles in female Sprague Dawley Rats. Computer fitting of the in vivo data and subsequent statistical testing enabled comparison of the effect of microsphere formation and the effect of microsphere dose on selected pharmacokinetic parameters.     

1H-Nuclear Magnetic Resonance Spectrosoopic Determination of Haloperidol in Tablets

A ¹H-nuclear magnetic resonance spectroscopic method was developed for the assay of haloperiodol in commercial tablets. Dimethylsulfoxide-d_b and 1,4-dinitrobenzene were used as the solvent and the internal standard, respectively. Recovery values of haloperidol (mean ± SD) from synthetic formulations were 99.8 ± 0.86% (CV = 0.86%, n = 10) by the proposed method, and 99.6 ± 0.80% (CV = 0.80%, n = 3) by the attrimetric method of USP XXI. Assay results for commercial 10 and 20 mg tablets agreed closely with those obtained by the compendial spectrophotometric method.     

Preparation of Gelatin: Phenytoin Sodium Microsphers: An IN VITRO and IN VIVO Evaluation

Abstract

In this study phenytoin sodium microspheres were formulated with biodegradable acid-treated gelatin. The microspheres were subjected to in vitro and in vivo testing. The percent drug retained in the microspheres, as well as its release from the microspheres, was tested. In vitro data revealed a decrease in percent druq retained in the microspheres with an increase in addition of glutaraldehyde to the microsphere formulations. The statistically most consistent drug release was observed from formulations containing 10 g of gelatin and 2 g of phenytoin sodium. From this formulation the slowest release was observed when 5 ml of glutaraldehyde were added to the various formulations, whereas the fastest release was observed when no glutaraldehyde was added. In vivo studies consisted of administering phenytoin sodium in microsphere form and an aqueous solution v i a various routes of administration and determining phenytoin plasma concentration vs. time profiles in female Sprague Dawley Rats. Computer fitting of the in vivo data and subsequent statistical testing enabled comparison of the effect of microsphere formation and the effect of microsphere dose on selected pharmacokinetic parameters.     

Pharmaceutical Analysis of β-Methyldigoxin in Dosage Forms Using RP-HPLC

A reversed-phase high-performance liquid chromatographic method has been developed for the assay of β-methyldigoxin in Dimekor® tablets (0.1 mg) and ampules (0.2 mg/2 mL). Quantitation of cardiac glycoside in mentioned dosage forms was carried out by the incorporation of phenacetin as an internal standard. A Varian HPLC configured with a Paltisil P10 ODS1 column was used for the separation and quantitation of β-methyldigoxin in pharmaceutical preparations. The mobile phase was acetonitrile-water 38: 62 v/v with flow rate 1.6 ml/min and UV detection was set at 220 nm. The range of linearity extended from 0.01 to 0.11 mg/mL. For the quantitative analysis of β-methyldigoxin in tablets the recovery was 100.16% and for ampules 99.50%. The excipients did not interfere with the determination of the analysed substance. The proposed method is precise and sensitive for the examination of examine the content uniformity of tablets and is in a good agreement with PH.JUG.IV (1). A spectrofluorimetric method was used for the dissolution test by the method described in USP XXII (2).     

Influence of Montmorillonite on the Dissolution and Bioavailablity of Phenyton

The dissolution of phenytoin were studied from various phentyoin-montmorillonite combinations. Firstly, phentoin-montmorllionite combinations were obtained by precipitating phenytoin from two different solvents on to montmorillonite using drug to montmorillonite ratios. Secondly, physical mixtures of phenytoin and montmorillonite were prepared in were compressed into tablets and the dissolution rates were determined. The dissolution rates of phenytoin with the dissolution rates of the combinations. The montmorillonite increased the dissolution rate of phenyton from all the combinations to such an extent that the dissolution rates compressed well with those obtained form phenytoin sodium.

The bioavailability of phentyoin from three different phenytoin-montmorillonite mixutres were compared well the bioavailability from a phenytoin sodium capsule in four volunters. More phenytoin were absorbed from the phenytoin-montrillonite mixtures than from the phenytoin sodium. The absorption rate of phenytoin from the three different montmorillonite mixtures were fastef than from the phenytoin sodium capsule for the first hour, after administtration. After one hour the phenytoin blood levels from the phenytoin-montmorillonite mixtures started to level of to reach lower peak concentrations in plasma than that obtained from phenytoin-montmorillonite mixtures (1:1 and 1:9 ratios) was more than that absorbed form phenytoin sodium. The advantages of combining phenytoin and montmorillonite for the improvement of the bioavailability of phenytoin have clearly been demonstrated.     

Method performance and validation for quantitative analysis by (1)h and (31)p NMR spectroscopy. Applications to analytical standards and agricultural chemicals

Nuclear magnetic resonance (NMR) can be used to provide an independent and intrinsically reliable determination of chemical purity. Unlike chromatography, it is possible to employ a universal reference standard as an internal standard for the majority of chemical products assayed by quantitative NMR (QNMR). This is possible because the NMR response can be made the same for all chemical components, including the internal standard, by optimizing certain instrumental parameters. Experiments were performed to validate the quantitative NMR method described in this paper for the analysis of organic chemicals. Experimental precision, accuracy, specificity, linearity, limits of detection and quantitation, and ruggedness were systematically addressed, and system suitability criteria were established. The level of the major chemical ingredient can be determined with accuracy and precision significantly better than 1%, and impurities may be quantified at the 0.1% level or below. Thus, QNMR rivals chromatography in sensitivity, speed, precision, and accuracy, while avoiding the need for a reference standard for each analyte. Examples are given of (1)H and (31)P NMR used for quantitative analysis of agricultural chemicals, and a method for characterization of analytical standards is presented.     

Comparison of Three Pharmaceutical Products Obtained from Mexico and the United States: A Case Study

ABSTRACT

In recent years, there has been much debate concerning the relative pros and cons of purchasing medications from foreign markets such as Mexico and Canada. The following study compares the content uniformity and weight variation for three medicinal products, acquired from pharmacies in both Mexico and the United States: amoxicillin capsules (500 mg), amoxicillin/clavulanic acid suspension (400 mg and 57 mg/5 mL, respectively), and furosemide tablets (40 mg). Twenty capsules/tablets were individually weighed and a designated aliquot was taken. Following dissolution in an appropriate solvent and sonication, a sample was taken and analyzed via high performance liquid chromatography (HPLC). The suspensions were prepared according to directions on the label. Five samples of the suspensions were then taken and analyzed via an appropriate HPLC method. The content uniformity for the amoxicillin capsules was found to be 15.4 ± 2.4% and 99.4 ± 9.3%, for Mexican and U.S. capsules, respectively. The percent relative standard deviation (% RSD) for weight variation was found to be 8.7% and 1.5% for capsules obtained from Mexico and the United States, respectively. Content uniformity analysis for the Mexican suspension product resulted in an average of 85.5 ± 1.2% for amoxicillin and 98.6 ± 1.9% for the clavulanic acid content, while the results for the U.S. suspension product were 104.4 ± 3.1% and 117.8 ± 3.6% for amoxicillin and clavulanic acid, respectively. Content uniformity for the furosemide tablets was found to be 90.3 ± 4.8% and 95.6 ± 2.1% for Mexican and U.S. tablets, respectively. The % RSD of weight variation for the Mexican tablets was 2.1%, while the % RSD for the U.S. tablets was found to be 1.0%. From the three products tested, content analysis revealed that the amount of active ingredients for two of the products acquired in Mexico were appreciably less than the concentrations for their U.S. counterparts.     

Pharmaceutical Analysis of β-Methyldigoxin in Dosage Forms Using RP-HPLC

Abstract

A reversed-phase high-performance liquid chromatographic method has been developed for the assay of β-methyldigoxin in Dimekor® tablets (0.1 mg) and ampules (0.2 mg/2 mL). Quantitation of cardiac glycoside in mentioned dosage forms was carried out by the incorporation of phenacetin as an internal standard. A Varian HPLC configured with a Paltisil P10 ODS1 column was used for the separation and quantitation of β-methyldigoxin in pharmaceutical preparations. The mobile phase was acetonitrile-water 38: 62 v/v with flow rate 1.6 ml/min and UV detection was set at 220 nm. The range of linearity extended from 0.01 to 0.11 mg/mL. For the quantitative analysis of β-methyldigoxin in tablets the recovery was 100.16% and for ampules 99.50%. The excipients did not interfere with the determination of the analysed substance. The proposed method is precise and sensitive for the examination of examine the content uniformity of tablets and is in a good agreement with PH.JUG.IV (1). A spectrofluorimetric method was used for the dissolution test by the method described in USP XXII (2).     

Comparison of three pharmaceutical products obtained from Mexico and the United States: a case study

In recent years, there has been much debate concerning the relative pros and cons of purchasing medications from foreign markets such as Mexico and Canada. The following study compares the content uniformity and weight variation for three medicinal products, acquired from pharmacies in both Mexico and the United States: amoxicillin capsules (500 mg), amoxicillin/clavulanic acid suspension (400 mg and 57 mg/5 mL, respectively), and furosemide tablets (40 mg). Twenty capsules/tablets were individually weighed and a designated aliquot was taken. Following dissolution in an appropriate solvent and sonication, a sample was taken and analyzed via high performance liquid chromatography (HPLC). The suspensions were prepared according to directions on the label. Five samples of the suspensions were then taken and analyzed via an appropriate HPLC method. The content uniformity for the amoxicillin capsules was found to be 15.4 ± 2.4% and 99.4 ± 9.3%, for Mexican and U.S. capsules, respectively. The percent relative standard deviation (% RSD) for weight variation was found to be 8.7% and 1.5% for capsules obtained from Mexico and the United States, respectively. Content uniformity analysis for the Mexican suspension product resulted in an average of 85.5 ± 1.2% for amoxicillin and 98.6 ± 1.9% for the clavulanic acid content, while the results for the U.S. suspension product were 104.4 ± 3.1% and 117.8 ± 3.6% for amoxicillin and clavulanic acid, respectively. Content uniformity for the furosemide tablets was found to be 90.3 ± 4.8% and 95.6 ± 2.1% for Mexican and U.S. tablets, respectively. The % RSD of weight variation for the Mexican tablets was 2.1%, while the % RSD for the U.S. tablets was found to be 1.0%. From the three products tested, content analysis revealed that the amount of active ingredients for two of the products acquired in Mexico were appreciably less than the concentrations for their U.S. counterparts.