Determination of ranitidine hydrochloride in pharmaceutical preparations by titrimetry and visible spectrophotometry using bromate and acid dyes

Four new methods using titrimetry and spectrophotometry are described for the determination of ranitidine hydrochloride (RNH) with potassium bromate as the oxidimetric reagent and acid dyes, methyl orange, indigo carmine and metanil yellow. In direct titrimetry (method A), the drug is titrated directly with bromate in acid medium and in the presence of excess of bromide using methyl orange indicator. In back titrimetry (method B), the drug is treated with a measured excess of bromate in the presence of bromide and acid, and the unreacted bromine is determined iodometrically. Both spectrophotometric methods are based on the oxidation of RNH by a known excess of bromate in acid medium and in the presence of excess of bromide followed by estimation of surplus oxidant by reacting with either indigo carmine (method C) or metanil yellow (method D), and measuring the absorbance at 610 or 530 nm. In methods B, C and D, reacted oxidant corresponds to the drug content. The experimental conditions are optimized. Titrimetric procedures are applicable over the ranges 1-10 mg (A) and 1-17 mg (B), and the reaction stoichiometry is found to be 1:1 (BrO(-)(3): RNH). In spectrophotometric methods, the absorbance is found to increase linearly with increasing concentration of RNH, which is corroborated by the calculated correlation coefficient (r) of 0.9984 (C) and 0.9976 (D). The systems obey Beer's law for 2-12 and 1-7 microg ml(-1), for methods C and D, respectively. Method D with a molar absorptivity of 9.82 x 10(4) l mol(-l) cm(-1) is found to be more sensitive than method C ( epsilon = 2.06 x l0(4) l mol(-1) cm(-1)). The limits of detection and quantification are reported for both the spectrophotometric methods. The proposed methods were applied successfully to the determination of RNH in tablets and injections. The reliability of the assay was established by parallel determination by the official method and by recovery studies.     

Use of Folin-Ciocalteu phenol reagent and 3-methyl-2-benzothiazolinone hydrazine hydrochloride in the determination of oxcarbazepine in pharmaceuticals

Two spectrophotometric methods are proposed for the assay of oxcarbazepine (OXC) in bulk and dosage forms using Folin-Ciocalteu phenol reagent (FCP) and 3-methyl-2-benzothiazolinone hydrazine hydrochloride (MBTH) as reagents. The first method involves addition of FCP reagent to OXC in alkaline medium followed by measurement of absorbance at 760 nm (method A), and the other involves addition of a fixed volume of MBTH after treatment of OXC with ferric chloride and measurement of absorbance at 456 nm (method B). In both methods, the amount of chromogen formed corresponds to the amount of OXC and the measured absorbance was found to increase linearly with the concentration of OXC, which is corroborated by the correlation coefficients of 0.9985 and 0.9984 for method A and B, respectively. The systems obey Beer's law for 5-30 microg mL(-1) and 10-50 microg mL(-1) for methods A and B, respectively. The apparent molar absorptivity was calculated to be 8.06 x 10(3) L mol(-1) cm(-1) and 3.126 x 10(3) L mol(-1) cm(-1) for methods A and B, respectively. The limits of detection (LOD) and limit of quantification (LOQ) were calculated to be 1.6 and 5 microg mL(-1) for method A and 3 and 10 microg mL(-1) for method B. The inter-day and intra-day imprecision of the methods were found to be in the range of 1.1-1.7 and 0.9-1.1% for method A, and 1.1-1.9 and 0.6-0.9% for method B. The accuracy ranged between 98.9-99.7% and 99.3-100.1 for method A and B, respectively. No interference was observed from common pharmaceutical excipients. The methods were successfully applied to the assay of OXC in tablet preparations.     

A sensitive spectrophotometric method for the determination of propranolol HCl based on oxidation bromination reactions

Three new, simple, sensitive, rapid and economical spectrophotometric methods (A, B and C) have been developed for the determination of propranolol hydrochloride (PRO) in bulk drug and dosage forms. These methods are based on oxidation‐bromination reaction of PRO by bromine, generated in situ by the action of acid on a bromate‐bromide mixture, followed by determination of unreacted bromine by three different reaction schemes. In method A, the determination of the residual bromine is based on its ability to bleach the indigo carmine dye and by measuring the absorbance at 610 nm. The residual bromine (in method B), is treated with excess of iron(II) and the resulting iron(III) is complexed with thiocyanate and the absorbance is measured at 480 nm. Method C involves treating the unreacted bromine with a measured excess of iron(II) and the remaining iron(II) is complexed with 1,10‐phenanthroline and the increase in absorbance is measured at 510 nm. In all three methods, the amount of bromine reacted corresponds to the drug content. The different experimental parameters affecting the development and stability of the colour are carefully studied and optimized. Beer's Law is valid within a concentration range of 1–13, 4–12 and 2–9 µg ml⁻¹ for methods A, B, and C, respectively. The molar absorptivity, Sandell's sensitivity, detection and quantification limits are calculated. Common excipients used as additives in pharmaceutical preparations do not interfere in the proposed methods. The proposed methods have been successfully applied to the determination of PRO in pharmaceutical preparations and the results were statistically compared with those of the official method by applying the Student's t‐test and F‐test. Copyright © 2010 John Wiley & Sons, Ltd.     

Simultaneous determination of 6,7-dimethylesculetin and geniposide in rat plasma and its application to pharmacokinetic studies of Yin Chen Hao Tang preparation

A method for the rapid and simultaneous determination of 6,7-dimethylesculetin (CAS 120-08-1) and geniposide (CAS 24512-63-8) in rat plasma has been developed, using validated high performance liquid chromatography (HPLC) with solid phase extraction (SPE). The HPLC analysis was performed on a commercially available column (200 mm x 4.6 mm, 5 microm) with acetonitrile-methanol-0.1% aqueous formic acid as mobile phase and the UV detection at 343 nm and 238 nm for 6,7-dimethylesculetin and geniposide, respectively. The calibration curves for 6,7-dimethylesculetin and geniposide were linear over the range 0.4-25.6 microg/mL and 1.12-71.68 microg/mL, respectively. The lower limits of quantitation were 0.40 microg/ mL and 1.12 microg/mL, and the lower limits of detection were 0.06 microg/mL and 0.09 microg/ mL, respectively. The intra-day and inter-day precision for 6,7-dimethylesculetin and geniposide were < 5%, whereas the absolute recovery percentages were > 74%. A successful application of the developed HPLC analysis was demonstrated for the pharmacokinetic study of a Traditional Chinese Medicine formula of Yin Chen Hao Tang preparation.     

Application of derivative spectrophotometry for determination of enalapril, hydrochlorothiazide and walsartan in complex pharmaceutical preparations

A derivative spectrophotometry method was developed to determine enalapril, hydrochlorothiazide, candesartan and walsartan in complex antihypertensive drugs. The pharmaceutical preparations containing hydrochlorothiazide and one of the angiotensin convertase inhibitors were investigated. It was found that the developed method enables the constituents of the investigated drugs to be determined directly despite evident interference of the zero order absorption spectra. For determination of enalapril and hydrochlorothiazide as well as candesartan and hydrochlorothiazide the first derivative was used, while for walsartan and hydrochlorothiazide the second derivative was employed. The method was of high sensitivity; the LOD accuracy for enalapril was 2.81 microg x mL(-1), 0.56 microg x mL(-1) for candesartan, 4.02 microg x mL(-1) for walsartan and ranged from 0.31 microg x mL(-1) to 1.78 microgxmL(-1) for hydrochlorothiazide, depending on preparation under investigation. The recovery of individual constituents was within the limit of 100% +/- 5%, RSD varied from 1.11% to 2.94%, and the linearity range was from 4.1 microg x mL(-1) to 20.5 microg x mL(-1) for enalapril, from 6.45 microg x mL(-1) to 32.25 microg x mL(-1) for walsartan, from 2.36 microg x mL(-1) to 11.80 microg x mL(-1) for candesartan, and from 0.96 microg x mL(-1) to 26.00 microg x mL(-1) for hydrochlorothiazide.     

Spectrophotometric determination of labetalol in pharmaceutical preparations and spiked human urine

Two simple and sensitive spectrophotometric methods were developed for the spectrophotometric determination of labetaolol (LBT). Both methods are based on the phenolic nature of the drug. The first method (Method I) is based on coupling LBT with diazotized benzocaine in presence of trimethylamine. A yellow colour peaking at 410 nm was produced and its absorbance is linear with the concentration over the range 1-10 microg ml(-1) with correlation coefficient (n=5) of 0.9993. The molar absorptivity was 2.633 x 10(4) l mol(-1) cm(-1). The second method (Method II) involves coupling LBT with diazotized p-nitroaniline in presence of sodium carbonate. An orange colour peaking at 456 nm was obtained and its absorbance is linear with concentration over the range 1-10 microg ml(-1) with correlation coefficient (n=5) of 0.99935. The stoichiometry of the reaction in both cases was accomplished adopting the limiting logarithmic method and was found to be 1:1. The developed method could be successfully applied to commercial tablets. The results obtained were in good agreement with those obtained using the official methods. No interference was encountered from co-formulated drugs, such as hydrochlorothiazide. The method was further extended to the in-vitro determination of LBT in spiked human urine. The % recovery (n=4) were 97.7+/-5.75 and 103.27+/-5.42 using the Methods I and II, respectively.     

High-performance liquid chromatography method for the determination of mycophenolic acid in human plasma and application to a pharmacokinetic study of mycophenolic acid dispersible tablet

A sensitive and selective high-performance liquid chromatographic-ultraviolet (HPLC-UV) method for the determination of mycophenolic acid (MPA, CAS 24280-93-1) in human plasma has been developed. Sample treatment was based on protein precipitation with a trichloroacetic acid-water (10:90, w/v) solution. The analytical determination was carried out by HPLC with ultraviolet detection at 254 nm. Chromatographic separation was achieved on a C18 column by isocratic elution with acetonitrile-water (pH 4.4) (50:50, v/v) at a flow rate of 1.0 mL/min. The method was linear in the concentration range of 0.2-50.0 microg/mL. The lower limit of quantification (LLOQ) was 0.2 microg/ mL. The intra-day and inter-day relative standard deviations across three validation runs over the entire concentration range were less than 7.05%. The accuracy determined at three concentrations (0.4, 5.0 and 20.0 microg/mL for MPA) was within +/- 10.0%. The method was successfully applied to the evaluation of the pharmacokinetic profile of MPA dispersible tablet in 20 healthy volunteers. The results showed that AUC, C(max) and T1/2 for the test and reference formulations were not significantly different (P > 0.05). The relative bioavailability was 96.42 +/- 15.5%.     

UV-spectrophotometric determination of imatinib mesylate and its application in solubility studies

A new, simple and sensitive UV-spectrophotometric method was developed for the determination of imatinib mesylate in bulk and pharmaceutical formulations (tablets and nanoparticles). The developed spectroscopic method was validated for selectivity, linearity and range, precision, accuracy and sensitivity. The method has demonstrated excellent linearity over the range of 2.5-25 microg/mL with regression equation: absorbance (AU) = 0.047 x concentration (microg/mL) + 0.008 and r2 = 0.9998. The developed method demonstrated consistent high recoveries (99-102%) and low relative standard deviation (< 5%) at 285 nm. Moreover, the method was found to be highly sensitive with low limit of detection (0.57 microg/mL) and limit of quantitation (1.71 microg/mL). The apparent molar absorptivity and Sandell's sensitivity was found to be 2.75 x 10(3) L/M cm and 2.15 microg/cm2 respectively. The validated method was successfully employed for the drug content analysis from tablets and nanoparticles preparations. Additionally, the method was successfully employed for pH metric solubility analysis of the drug.     

Comparison of zero- and second-order derivative spectrophotometric and HPLC methods for the determination of gemcitabine in human plasma

Zero- and second-order derivative spectrophotometric and high-performance liquid chromatography (HPLC) methods were developed and validated for the determination of gemcitabine in human plasma. Spectrophotometrically, gemcitabine was determined by means of zero-order derivative absorbance values (A) at 288 nm and from values from the second-order derivative absorbance values (2D) at 285 nm. Beer's Law was obeyed in the range 0.50-15.0 microg ml(-1). The proposed other method, normal-phase HPLC method for determination of gemcitabine in human plasma was described. Calibration curve was linear over the concentration range 0.20-15.0 microg ml(-1). Quantitation was achieved by diode array detection at 272 nm using 2'-deoxycytidine as internal standard. Results obtained by spectrophotometric and HPLC methods for determination of gemcitabine in human plasma described in this paper showed adequate accuracy, precision and repeatability. No interference was found in plasma at the selected derivative wavelength and chromatographic conditions. According to the statistical comparison, there is no significant difference between the three methods. This is suggested that the three methods are equally applicable.     

Application of ion-pair complexation reaction for the spectrophotometric determination of bupropion hydrochloride in pharmaceuticals

This is the first report on the use of visible spectrophotometry for the determination of bupropion hydrochloride (BUPH), a second-generation antidepressant, in pharmaceuticals. Two sensitive, selective, and cost-effective spectrophotometric methods are described. The first method (method A) is based on the formation of yellow-coloured ion-pair complex between the BUPH and methyl orange (MO) at pH 3.80 ± 0.10 which was extracted into dichloromethane and the absorbance measured at 425 nm. The second method (method B) is based on the breaking of the yellow BUPH-MO ion-pair complex in acid medium followed by the measurement of the red-pink colour at 520 nm. Beer's Law is obeyed over the concentration ranges of 1.00-12.0 and 0.48-7.20 μg ml(-1) BUPH for method A and method B, respectively. The molar absorptivities are calculated to be 2.18 × 10(4) and 3.79 × 10(4) l mol(-1) cm(-1) for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.0127 and 0.0073 μg cm(-2) . The limits of detection and quantification have also been reported. The proposed methods were applied successfully to the determination of BUPH in pure drug and commercial tablets. The accuracy and reliability of the proposed methods were further ascertained by recovery studies via standard addition technique.     

Effect of adsorbents on the absorption of lansoprazole with surfactant

Lansoprazole (LPZ) is a representative drug that shows a high inter-subject variation of bioavailability (BA). Solid preparation composed of surfactant, adsorbent and LPZ were prepared to improve the dissolution and absorption of LPZ, and the BA of LPZ was measured in rats and dogs. As surfactant, Tween 80, polyoxy 60 hydrogenated caster oil derivative (HCO-60) and PEG-8 caprylic/capric glycerides (Labrasol) were used. As adsorbant, porous silicon dioxide (Sylysia 550, 320), magnesium aluminometa silicate (Neusilin S2, NS2N, US2) and porous calcium silicate (Florite RE) were used. After small intestinal administration of LPZ, 5.0 mg/kg, solution with HCO-60 showed the highest plasma LPZ concentration versus time curve of which C(max) and AUC was 0.46+/-0.01 microg/mL and 0.73+/-0.03 microgh/mL. By comparing to that after i.v. injection of LPZ solution, 2.0 mg/kg, the BA of LPZ from HCO-60 solution was 39.0%, which was about seven times higher than that of LPZ powder. To solidify the LPZ solution with HCO-60, adsorbents were used and the obtained solid preparations were used for in vitro release experiment. Sylysia 320, Neusilin S2 and Neusilin NS2 showed the T50% of about 1h. To evaluate the BA of these solid preparations, absorption study was performed in rats. Sylysia 550 system showed the higher AUC than other systems, showing the BA of 28.1%. Sylysia 550 system was filled in an enteric capsule and was orally administered to dogs and BA was compared with enteric tablet. The AUC of Sylysia 550 system was 2.16+/-0.26 microgh/mL and was greater than enteric tablet and the BA of 71.7% was obtained. Solid system composed of LPZ, surfactant and adsorbent has suggested the possibility as a good tool to improve the BA of LPZ.     

Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and UGT2B7

Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.     

Comparison of UV spectrophotometric method and high performance liquid chromatography for the analysis of flunarizine and its application for the dissolution test

This study aimed to develop a simple UV spectrophotometric method for the analysis and the dissolution test of flunarizine in capsules. The UV absorbance was both measured directly and by the first derivative measurements at 254 and 268 nm, respectively. The developed methods were validated for their linearity, accuracy, precision, limit of detection (LOD) and limit of quantitation (LOQ) in comparison with the reported HPLC method. The UV spectrophotometric method illustrated excellent linearity (r2 > 0.9999) in the concentration range of 6-24 microg/mL. Precision (%R.S.D. < 1.50) and recoveries were good (%R > 99.62). The LOD of direct UV and first derivative measurements were 0.09 and 0.84 microg/mL, respectively, and the LOQ were 0.26 and 2.55 microg/mL, respectively. Results from the assay of flunarizine in capsules by the UV spectrophotometric methods, both direct and first derivative measurements were not significantly different from those of the HPLC method (P > 0.05). Additionally, the method was successfully used for the dissolution test of flunarizine capsule and was found to be reliable, simple, fast, and inexpensive.     

Quantitation of free and total amphotericin B in human biologic matrices by a liquid chromatography tandem mass spectrometric method

Amphotericin B remains the standard of care for the treatment of invasive and disseminated fungal infections. Various lipid-based formulations of amphotericin B have been developed to improve its therapeutic index by decreasing toxicity. Previous bioanalytic methods using microbial inhibition or high-pressure liquid chromatography quantified total amphotericin B (free, plasma protein-bound, and lipid-complexed). Sensitivity of this method with a low limit of quantitation of 0.05 microg/mL was inadequate to determine free (unbound) amphotericin B. A sensitive LC/MS/MS method was developed to determine the total amphotericin B value in human plasma and other biologic matrices and the free amphotericin B concentration in plasma. For determination of total plasma amphotericin B concentrations, the sample was diluted and injected onto the LC/MS/MS. For total amphotericin B in other matrices and free amphotericin B in plasma, solid-phase extraction was used. Natamycin served as an internal standard. A PE Sciex API 3000 (Sciex; Concord, Ontario, Canada) was used to assess free amphotericin B in plasma ultrafiltrate determination and an API 3+ for the other matrices, with electrospray interfaced to a C18 analytic column. The low limit of quantitation was 1 ng/mL for ultrafiltrate. For total amphotericin B, the low limits were 2 microg/mL for plasma, 0.05 microg/mL for urine, and 0.4 microg/mL for fecal homogenate. The methods were validated to show the standard range linearity, sensitivity, selectivity, accuracy, precision, and stability of amphotericin B in the matrices tested.     

Simultaneous determination of triamterene and hydrochlorothiazide in tablets using derivative spectrophotometry

A quick and accurate method for determining triamterene and hydrochlorothiazide in complex drugs of diuretic activity by using first-derivative (D1) and second-derivative (D2) spectrophotometry was developed. The zero-crossing technique was employed in measurements, using D1 at lambda = 240.9 nm and D2 at lambda= 278.2 nm for determining triamterene and D1 at lambda = 255.7 nm and D2 at lambda = 283.2 nm for hydrochlorothiazide. The linear relationship between the values of derivatives and analyte concentrations are maintained for concentrations from 2.40 microg x mL(-1) to 12.00 microg x mL(-1) for triamterene and from 1.25 microg x mL(-1) to 6.25 microg x mL(-1) for hydrochlorothiazide. LOD for triamterene was 0.90 microg x mL(-1) or 1.02 microg x mL(-1), while LOQ was 2.73 microg x mL(-1) or 3.08 microg x mL(-1). The corresponding values for hydrochlorothiazide were: LOD 0.25 microg x mL(-1) or 0.17 microg x mL(-1) and LOQ 0.77 microg x mL(-1) or 0.51 microg x mL(-1) depending on the derivative used. The determination results of drug constituents are of high accuracy, percentage recovery ranging from 97.17% to 99.74% for triamterene and from 102.44% to 102.64% for hydrochlorothiazide, and good precision. The computed values of RSD are smaller than 2.73% for triamterene and below 1.63% for hydrochlorothiazide. Selectivity and sensitivity of the developed method are satisfactory.     

Spectrophotometric determination of fluoxetine hydrochloride in bulk and in pharmaceutical formulations

Two new rapid, sensitive and economical spectrophotometric methods are described for the determination of fluoxetine hydrochloride in bulk and in pharmaceutical formulations. Both methods are based on the formation of a yellow ion-pair complex due to the action of methyl orange (MO) and thymol blue (TM) on fluoxetine in acidic (pH 4.0) and basic (pH 8.0) medium, respectively. Under optimised conditions they show an absorption maxima at 433 nm (MO) and 410 nm (TB), with molar absorptivities of 2.12 x 10(-4) and 4.207 x 10(-3) l mol(-1) cm(-1) and Sandell's Sensitivities of 1.64 x 10(-2) and 0.082 microg cm(-2) per 0.001 absorbance unit for MO and TB, respectively. The colour is stable for 5 min after extraction. In both cases Beer's Law is obeyed at 1-20 microg mol(-1) with MO and 4-24 microg mol(-1) with TB. The proposal method was successfully extended to pharmaceutical preparations capsules. The results obtained by both the agreement and E.P. (3rd edition) were in good agreement and statistical comparison by Student's t-test and variance ratio F-test showed no significant difference in the three methods.     

Pharmacokinetics and bioequivalence study of clindamycin hydrochloride formulations after single-dose administration in healthy Chinese male volunteers

The aim of the present study was to compare the bioavailability of clindamycin (CAS 18323-44-9) from three clindamycin hydrochloride (CAS 21 462-39-5) capsules (clindamycin 75 mg capsule as test 1 preparation, 150 mg capsule as test 2 preparation and a commercially available original 150 mg capsule of the drug as reference preparation) in 24 Chinese healthy male volunteers, aged between 22 and 28. The study was conducted according to a randomized, double-blind, 3-period, 3-treatment, 3-sequence, single-dose, crossover design with a wash-out phase of 7 days. Blood samples for pharmacokinetic profiling were taken up to 14 h post-dose, and clindamycin plasma concentrations were determined with a validated liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Maximum plasma concentrations (C(max)) of 3.06 +/- 1.10 microg/mL (test 1), 3.10 +/- 1.59 microg/mL (test 2) and 3.06 +/- 1.15 microg/mL (reference) were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity)) of 10.73 +/- 4.29 microg x h/mL (test 1), 10.54 +/- 4.10 microg x h/ mL (test 2) and 11.29 +/- 4.98 microg x h/mL (reference), AUC(0-t) of 10.32 +/- 4.09 microg x h/ mL, 10.26 +/- 3.96 microg x h/mL, 10.94 +/- 4.86 g x h/mL were calculated. The median T(max) was 0.80 +/- 0.52 h, 0.77 +/- 0.37 h, 1.01 +/- 0.6 h for test 1, test 2 and reference formulation, respectively. Plasma elimination half-lives (t1/2) of 2.72 +/- 0.58 h (test 1), 2.39 +/- 0.37 h (test 2) and 2.63 +/- 0.66 h (reference) were determined. Both primary target parameters, AUC(0-infinity) and AUC(0-t) were tested parametrically by analysis of variance (ANOVA) and relative bioavailabilities were 98.0 +/- 16.2% (test 1) and 97.2 +/- 20.3% (test 2) for AUC(0-infinity), 97.5 +/- 16.3% (test 1) and 97.8 +/- 20.2% (test 2) for AUC(0-t). Bioequivalence between test and reference preparation was demonstrated for both parameters, AUC(0-infinity) and AUC(0-t). The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%. That means that the two test formulations are bioequivalent to the reference formulation for clindamycin.     

A validated UV spectrophotometric method for determination of duloxetine hydrochloride

A simple, sensitive and accurate UV spectrophotometric method was developed for the assay of duloxetine hydrochloride in raw material and capsules. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The absorbance was measured at 290 nm for duloxetine capsule solution. The linearity range was found to be 5-50 microg/mL for the drug. It was found that the excipients in the commercial formulation did not interfere with the methods.     

Selective and validated spectrophotometric methods for the determination of nicorandil in pharmaceutical formulations

Two simple and sensitive validated spectrophotometric methods have been described for the assay of nicorandil in drug formulations. Method A is based on the reaction of the drug with phloroglucinol-sulfanilic acid reagent in sulfuric acid medium to give yellow-colored product, which absorbs maximally at 425 nm. Method B uses the oxidative coupling of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with DL- 3,4 - dihydroxyphenylalanine (DL-dopa) in the presence of nicorandil as oxidant in sulfuric acid medium to form an intensely colored product having maximum absorbance at 530 nm. Beer's law is obeyed in the concentration range 2.5 to 50.0 and 1.0 to 15.0 microg mL(-1) with methods A and B, respectively. Both methods have been successfully applied for the analysis of drug in pharmaceutical formulations. The reliability and the performance of the proposed methods are established by point and interval hypothesis and through recovery studies. The experimental true bias of all samples is smaller than +/-2%.     

Evaluation of fast disintegrating lansoprazole tablet in human subjects

Fast disintegrating lansoprazole tablet (LFDT) has been developed as a multiple unit formulation and evaluated using human subjects as compared to the conventional lansoprazole (LPZ) capsule containing enteric coated granules. Twelve healthy male volunteers, who were confirmed as extensive metabolizers (EMs) based on the plasma levels of LPZ sulphone metabolite, were enrolled into the study and genotype of CYP2C19 was confirmed. They kept 30 mg LFDT in their mouths for 2 min and the saliva was recovered without swallow. Eight subjects did not show LPZ in their serum after intake. Although LPZ was detected in 4 subjects' serum, their concentrations were less than 5 ng/mL. LPZ was thought to be not absorbed from the oral cavity. LFDT was orally administered to 12 healthy male EMs at two doses, 15 mg and 30 mg, and serum LPZ concentrations were measured. The mean C(max) and AUC(0-24) were 474.1+/-254.0 ng/mL and 1105.3+/-1101.4 ng.h/mL (15 mg) and 992.8+/-384.3 ng/mL and 2216.5+/-1270.1 ng.h/mL (30 mg). By comparing to that obtained after oral administration of the same doses of LPZ capsule, serum LPZ concentration vs. time curve was almost the same level, i.e., C(max) and AUC(0-24) did not have significant differences. From these results, LFDT has been shown to be equivalent to LPZ capsule and will show the same acid suppressing effects in the clinical situation.