Phentolamine bioequivalence study

Objective: To assess the bioequivalence of 2 tablet formulations of phentolamine (Regitine phentolamine 40 mg tablet formulation by Novartis, Brazil, as test formulation, and Vasomax, phentolamine 40 mg tablet formulation by Schering Plough S.A., Brazil, as reference formulation). Methods: A single 40 mg oral dose of each formulation was administered to 36 male healthy volunteers. The study was conducted after screening, using an open, randomized, 2-period crossover design, a 7-day interval between doses, and wash-out period of at least 4 weeks. Plasma samples for determination of phentolarnine were obtained predose and at intervals over 720 min postdose. Plasma concentrations were quantified by reversed-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM) method. Precision of the method was evaluated using calibration curves and plasma quality control samples. The subjects were monitored throughout the study. Systolic and diastolic blood pressure and pulse rate measurement were taken predose and at intervals up to 720 min. Tolerance of both products was good. No serious adverse reactions were reported. The pharmacokinetic parameters calculated for both compounds included: AUC((0-720 min)), AUC((0-infinity)), C-max,C- C-max/AUC((0-720 min),) t(max), t(1/2) and k(c). Results: the maximum concentrations reached (Cmax) were compared. Regitine 40 mg formulation C-max geometric mean ratio was 108.29% (90% Cl = 98.58 - 118.96) of Vasomax 40 mg formulation. The areas under the curve (AUC((0-720 min))) were compared. Regitine 40 formulation (AUC((0-720 min)) geometric mean ratio was 102.33% (90% Cl = 97.21 - 107.72) of Vasomax 40 mg formulation. Conclusion: Since the 90% Cl for both Cmax and AUC ratio where inside the 80 to 125% interval proposed by the Food and Drug Administration, it is concluded that Regitine 40 mg tablet is bioequivalent to Vasomax for the rate and extent of absorption.

Effectiveness and safety of a new vaginal misoprostol product specifically labeled for cervical ripening and labor induction

Objective. The purpose of this study was to evaluate the effectiveness and safety of misoprostol in two different formulations: vaginal tablets of 25 mu g and one-eighth of a 200-mu g oral tablet, also administered intravaginally, for cervical ripening and labor induction of term pregnancies with an indication for that. Methods. A single-blind, randomized, controlled clinical trial was carried out in 120 pregnant women who randomly received one of the two formulations. The main dependent variables were mode of delivery, need for additional oxytocin, time between beginning of induction and delivery, perinatal results, complications, and maternal side effects. Student's t, Mann-Whitney, chi(2), Fisher's Exact, Wilcoxon and Kolmogorov-Smirnoff tests, as well as survival analysis, were used in the data analysis. Results. There were no significant differences between the groups in terms of general characteristics, uterine contractility, and fetal well-being during labor, cesarean section rates, perinatal outcomes, or maternal adverse events. The mean time between the beginning of cervical ripening and delivery was 31.3 h in the vaginal tablet group and 30.1 h in the oral tablet group, a difference that was not statistically significant. Conclusion. The results showed that the 25-mu g vaginal tablets of misoprostol were as effective and safe for cervical ripening and labor induction as the dose-equivalent fraction of 200-mu g oral tablets.

Porosity measurement of solid pharmaceutical dosage forms by gamma-ray transmission

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A Validated Stability-Indicating LC Method for Orbifloxacin in the Presence of Degradation Products

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CELULOSE FIBROSA DO BAGACO DA CANA-DE-ACUCAR - AVALIACAO DA ACAO AGLUTINANTE/DESAGREGANTE EM COMPRIMIDOS CONTENDO FARMACO HIDROSSOLUVEL

In this work, a fibrous cellulose obtained from the sugar cane bagasse was analysed about its binder/disintegrating action and about its interference degree in the dissolution rate ('in vitro') of active principles, when incorporated in a compact system that has a water-soluble drug. It was used as reference drug the Lithium Carbonate, considering its solubility in water and it difficulties in the compressibility and flow rate. That cellulose was evaluated in a comparative study, involving another fibrous cellulose generally used in the tablet obtainment (Microcel 3E-200). After the experiment in methodologies of dry granulation and wet granulation, it was concluded that the analysed celluloses presents adequate binder/disintegrating efficience and they are equivalents in these aspect.

EFICACIA E TOLERABILIDADE DA ASSOCIACAO CAPTOPRIL + HIDROCLOROTIAZIDA NO TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE A MODERADA. ESTUDO MULTICENTRICO

Purpose. To evaluate the antihypertensive efficacy and tolerability of captopril 50 mg + hydrochlorothiazide 25 mg daily in mild to moderate primary hypertension. Methods. Out-patients (n = 471) with mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with 15 days of washout, were included to the treatment initially with half tablet of the association of captopril 50 mg + hydrochlorothiazide 25 mg once daily, for 30 days. After this period, patients with DBP > 90 mmHg had the dosage duplicated, while the others had the same dosage for 60 days more. Evaluation was performed 15 days before and then every month during active drug. Results. Twenty six patients were withdrawn, 13 (2,7%) by adverse effects and 13 by protocol violation. At the end of the wash-out period, the blood pressure (BP), 162 ± 16/103 ± 6 mmHg decreased significantly at the 30th day to 146 ± 14/92 ± 8 mmHg (p < 0,001 vs 0th day); 139 ± 12/86 ± 7 mmHg at the 60th day, (p < 0,001 vs 30th day), and further to 136 ± 11/84 ± 5 mmHg (p < 0,001 vs day 0) till the end of the 90th day. Antihypertensive efficay (DBP ≤ 90 mmHg and decreased for the DBP ≥ 10 mmHg) was obtained in 82% of the patients. There was no difference in BP control considering race, hypertension level, previous antihypertensive treatment and obesity. Cough (4%) was the main adverse event. Conclusion. Captopril + hydrochlorothiazide was effective and safe in the treatment of mild to moderate hypertension. The favorable response was observed in 82% of the patients independently of race, hypertensive level, previous antihypertensive treatment and obesity. Low incidence of side effects was reported, with no difference from others reported in the literature.

Avaliacao preliminar da utilizacao do residuo industrial de man dioca (manihot esculenta granz) como excipiente em comprimidos: Caracteristicas fisicas e de compressao

The applicability of a residue of manioc (Manihot esculenta Granz) from industrial processing as a direct compression excipient was investigated in comparison with microcrystalline cellulose (Avicel® PH 101). Physical characteristics of the powders like bulk and tap densities, particle size, flow properties (flow rate, index of compressibility and angle of repose) and agglutination were evaluated. The residue had poor performance as excipient for direct compression. However, it showed better disintegration properties than Avicel. The possibility of its use as disintegrant agent will be confirmed on future studies.

Performance characteristics of bioassay, UV-spectrophotometry and high performance liquid chromatographic determination of sparfloxacin in tablets

The microbiological bioassay, the UV-spectrophotometry and the high performance liquid chromatography (HPLC) methods for assaying sparfloxacin in tablets were compared. The accuracy, repeatability, and precision of each method was assessed and precise. All methods were reliable within acceptable limits for antibiotic pharmaceutical preparations being accurate and precise. The microbiological bioassay and HPLC are more specific than UV-spectrophotometric analysis. However, the microbiological bioassay requires 20 h to get results, and HPLC is the most expensive analysis. The application of each method as a routine analysis should be investigated considering cost, simplicity, equipment, solvents, speed, and application to large or small workloads.

Analise citotoxica de esparfloxacino e seus produtos de degradaçao em células mononucleares humanas

Sparfloxacin, a difluorquinolone derivative, is a potent antibacterial agent active against a wide range of gram-positive and gram-negative organisms including Streptococcus pneumoniae, Staphylococcus aureus, methicillin resistant S. aureus, Legionella spp, Mycoplasma spp; Chlamydia spp. and Mycobacteria. A drawback of fluorquinolones is their photoreactivity. Sparfloxacin has been studied in terms of therapeutic activities. However, few reports about analytical methods of sparfloxacin are available in the literature. The aim of this study was to determine cytotoxic effects, using sparfloxacin reference substance (SPAX-SR), sparfloxacin tablets (SPAX-COMP) and sparfloxacin tablets submitted UV light during 36 hours (SPAX-COMP.36) solution, and two isolated products (7 and 9) of SPAX-SR submitted UV-C light, in concentrations of 31.25, 62.5, 125 and 250 μg/mL by in vitro mononuclear humane culture cells. The results, statistically analyzed by Teste de Tukey, showed SPAX, SPAX-COMP and SPAX-COMP.36 solutions could reduce the cells number in these conditions. These results could not be observed for products 7 or 9. These results can suggest that isolated product can be less cytotoxic than SPAX-SR, is method can also be used to identified products degradation of sparfloxacin in stability study. However, the low activity achieved with sparfloxacin submitted to UV-light is a source of concern and requires further investigation about its photodegradation mechanism.

Non-aqueous Titration of Gatifloxacin in Pharmaceutical Formulations using Perchloric Acid

An inexpensive, simple, precise and rapid method for the determination of fluoroquinolone gatifloxacin in tablets is described. The procedure is based on the use of volumetric dosage in a non-aqueous medium in glacial acetic acid with 0.1 M perchloric acid. The method validation yielded good results and included the precision, recovery and accuracy. It was also found that the excipients in the commercial tablet preparation did not interfere with the assay.

Development and validation of an UV spectrophotometric method for determination of gatifloxacin in tablets

A simple, sensitive and accurate spectrophotometric method was developed for the assay of gatifloxacin in raw material and tablets. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The absorbance was measured at 287 nm for gatifloxacin tablet solutions. The linearity range was found to be 4.0-14.0 μg/mL for gatifloxacin. It was also found that the excipients in the commercial tablets did not interfere with the method.

Determination of flutamide in tablets by high-performance liquid chromatography

Flutamide is a potent antiandrogen used for the treatment of prostatic cancer. A simple, sensitive and accurate high-performance liquid Chromatographic (HPLC) method is presented for quantitative determination of flutamide in tablets, using a reversed-phase technique and UV detection at 240 nm. The isocratic elution was used to quantify the analyte. The samples were chromatographed on Luna-C18 column and the mobile phase was 0.05 M phosphate buffer pH 4.0 - acetonitrile (50:50, v/v). The method was linear between 2.9 - 11.6 mg L -1. Over the tested concentration range the intra-day relative standard deviation for replicate analysis in tablets ranged from 0.44 to 0.78%. It was also found that the excipients in the commercial tablets did not interfere with the method.

Validation of UV spectrophotometric method for determination of lomefloxacin in pharmaceutical dosage form

A simple and reproducible method was developed for the assay of lomefloxacin in tablets. The excipients in the commercial tablet preparation did not interfere with the assay. Beer's law is obeyed in the range 2.0-9.0 μg.mL-1 at λmax 280 nm. The molar absorptivity was calculated. Six triplicate analyses of solutions containing six different concentrations of the examined drug were carried out and gave a mean correlation coefficient 0.9997. The proposed method was applied to the determination of the examined drug in coated tablet and the results demonstrated that the method is equally accurate, precise and reproducible as the official methods.