Determination of phenobarbital in human plasma by a specific liquid chromatography method: application to a bioequivalence study

A liquid chromatography method was developed and validated for the determination of phenobarbital in human plasma using phenytoin as internal standard. The drugs were extracted from plasma by liquid-liquid extraction and separated isocratically on a C12 analytical column, maintained at 35 ºC, with water:acetonitrile:methanol (58.8:15.2:26, v/v/v) as mobile phase, run at a flow rate of 1.2 mL/min with detection at 205 nm. The method was linear in the range of 0.1-4 μg/mL (r²=0.9999) and demonstrated acceptable results for the precision, accuracy and stability studies. The method was successfully applied for the bioequivalence study of two tablet formulations (test and reference) of phenobarbital 100 mg after single oral dose administration to healthy human volunteers.

Tecnologia de nanocristais em fármacos

The use of poorly water soluble molecules in pharmaceutical area has grown. Since these molecules exhibit low oral bioavailability, they are not used in intravenous administrations. Therefore, it is necessary to develop their new formulations with the aim to increase their oral bioavailabilities as to enable intravenous applications. One of the few possibilities in achieving this is a nanonization process that can produce crystals smaller than 1 μm by high pressure homogenization and without use of organic solvents. This mini-review describes technical aspects of the nanocrystal production, morphological aspects (polymorphisms), the market relevance of the nanocrystals products that are already in clinical phase or at the market, as well as, perspectives for the near future.

Desenvolvimento de um método reflectométrico ambientalmente mais amigável para a determinação de metoclopramida em formulações farmacêuticas

A simple and more environmentally friendly method by combined spot test-diffuse reflectance spectroscopy for determining metoclopramide in pharmaceutical formulations is described. The method is based on the reaction between metoclopramide and p-dimethylaminocinnamaldehyde, in the presence of HCl, producing a colored compound (λmáx = 580 nm) on the filter paper. The linear range was from 5.65 x 10-4-6.21x10-3 mol L-1 (r = 0.999). The limit of detection was 1.27 x 10-4 mol L-1. The proposed reflectometric method was applied successfully to the determination of metoclopramide in pharmaceuticals and it was favorably compared with the Brazilian or British Pharmacopoeia methods at 95% confidence level.

Determinação de sibutramina em formas farmacêuticas através de espectroscopia no infravermelho com refletância difusa e métodos de calibração multivariada

The goal of this work is the development and validation of an analytical method for fast quantification of sibutramine in pharmaceutical formulations, using diffuse reflectance infrared spectroscopy and partial least square regression. The multivariate model was elaborated from 22 mixtures containing sibutramine and excipients (lactose, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate) and using fragmented (750-1150/ 1350-1500/ 1850-1950/ 2600-2900 cm-1) and smoothing spectral data. Using 10 latent variables, excellent predictive capacity were observed in the calibration (n=20, RMSEC=0.004, R= 0.999) and external validation (n=5, RMSEC= 9.36, R=0.999) phases. In the analysis of synthetic mixtures the precision (SD=3,47%) was compatible with the rules of the Agencia Nacional de Vigilância Sanitária (ANVISA-Brazil). In the analysis of commercial drugs good agreement was observed between spectroscopic and chromatographic methods.

Determinação espectrofotométrica de cefalexina em formulações farmacêuticas explorando a sua reação de transferência de carga com a quinalizarina

This work proposes a new simple and fast spectrophotometric method for cephalexin determination in pharmaceutical formulations. The method is based on the charge transfer reaction between cephalexin and quinalizarin in dimethylsulfoxide medium. Several analytical parameters related to the system were optimized and the reaction was characterized in terms of stoichiometry. Also, association constant and apparent molar absorptivity of the product were determined. The method presented a limit of detection of 0.46 mg L-1 and a quantification limit of 1.5 mg L-1. It was successfully applied in the determination of cephalexin in two samples of commercial pharmaceutical formulations.

Development and validation of UV spectrophotometric method for determination of levofloxacin in pharmaceutical dosage forms

The objective of this research was to develop and validate an alternative analytical method for quantitative determination of levofloxacin in tablets and injection preparations. The calibration curves were linear over a concentration range from 3.0 to 8.0 μg mL-1. The relative standard deviation was below 1.0% for both formulations and average recovery was 101.42 ± 0.45% and 100.34 ± 0.85% for tablets and injection formulations, respectively. The limit of detection and limit of quantitation were 0.08 and 0.25 μg mL-1, respectively. It was concluded that the developed method is suitable for the quality control of levofloxacin in pharmaceuticals formulations.

Simultaneous determination of gemifloxacin and diuretics in bulk, pharmaceutical dosage forms and human serum by RP-HPLC

An isocratic reversed phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of gemifloxacin and diuretics (hydrochlorothiazide and furosemide) in bulk, dosage formulations and human serum at 232 nm. Chromatographic separation was achieved on Purospher Start C18 (250 mm x 4.6 mm, 5 µm) column using mobile phase, methanol: water: acetonitrile (70:25:5 v/v/v) adjusted to pH 3.0 via phosphoric acid 85% having flow rate of 0.8 mL min -1 at room temperature. Calibration curves were linear over range of 0.5-10 µg mL -1 with a correlation coefficient ± 0.999. LOD and LOQ were in the ranges of 0.75-2.56 µg mL -1. Intra and inter-run precision and accuracy results were 98.26 to 100.9.

Análise térmica aplicada à caracterização da sinvastatina em formulações farmacêuticas

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are used in pharmaceutical studies for drugs characterization, purity, formulations compatibility, polymorphism identification, stability evaluation, and thermal decomposition of drugs and pharmaceutical formulations. Simvastatin showed fusion at 138.5 ºC and thermal stability up to 248 ºC. Simvastatin was incompatible with preservative excipient butylhydroxyanisole (BHA) performing a process of crystal amorphization. The drug showed morphological polymorphism, where it has the same unit cell but with different crystal habits according to the recrystallization solvent.

Viscoelásticos oftálmicos: comparação entre os comerciais e formulações de galactomanana de Dimorphandra gardneriana

Ophthalmic viscosurgical devices (OVD) are materials injected in intraocular space during cataract removal to reduce trauma in the patient's eye. Three Brazilian commercially available OVDs (Medilon®, Metilcelulose® and Ofthyal®) were evaluated as well as formulations based on Dimorphandra gardneriana galactomannan. Viscosity and viscoelastic parameters, such as viscosity at zero shear, pseudoplasticity index, elastic and viscous moduli, relaxation time, were determined and compared. Characteristics of an effective OVD were proposed. None of the Brazilian devices studied fulfill the rheological requirements. Only the galactomannan at 3% concentration showed potential to be used as effective OVD.

Caracterização físico-química do fármaco antichagásico benznidazol

Currently, benznidazole (BNZ) is a unique therapeutic alternative available in Brazil to treat Chagas disease. Despite its traditional medical use, little is known about the chemical nature of this drug. A detailed study of the physicochemical properties of BNZ was performed using multiple assays. Thermal, diffractometric, morphological and reological drug profiles were obtained. The partition coefficient and solubility results allowed this drug to be classified as a class IV drug according to the biopharmaceutical classification system. This information will be useful for the development of more effective BNZ formulations and for establishing the quality profile of BNZ.

Preparação e caracterização de suspensões coloidais de nanocarreadores lipídicos contendo resveratrol destinados à administração cutânea

Solid lipid nanoparticles (SLN), nanoemulsions (NE), and microemulsions (ME) were prepared by the hot solvent diffusion method, using tristearin or castor oil as oily phase, and soy lecithin and Solutol HS 15 as surfactants. Mean particle sizes ranged from 20 to 215 nm and negative zeta potentials were obtained for all nanocarriers. A HPLC method used to determine resveratrol was specific, linear, exact and precise. The entrapment efficiency was high for all formulations. However, resveratrol content was significantly varied among the lipid nanocarriers. Lipid nanocarrier containing hydrogels exhibiting pseudoplastic behavior were obtained after incorporation of hydroxyethylcellulose in the colloidal dispersions.

Chemical stability of enalapril maleate drug substance and tablets by a stability-indicating liquid chromatographic method

The chemical stability of enalapril drug substance and tablets was studied by a stability-indicating liquid chromatographic method. Stress testing was performed on drug substance under various conditions. Accelerated stability testing was carried out for different formulations of enalapril tablets. Chromatographic separation was achieved on a RP-18 column, using a mobile phase of methanol phosphate buffer at 1.0 mL min"1 and UV detection. Degradation of the drug substance was greater under hydrolytic conditions. After 180 days of accelerated stability testing most enalapril tablets showed more than 10% of degradation. Enalapril drug substance and tablets showed instability under stress and accelerated testing respectively, with possible implications on the therapeutic activity.

Nanostructured systems containing an essential oil: protection against volatilization

The goal of this study was to evaluate the feasibility of preparing nanocapsules and nanoemulsions using tea tree oil as oily phase aiming to protect its volatilization. The nanostructures presented nanometric mean size (160-220 nm) with a polydispersity index below 0.25 and negative zeta potential. The pH values were 6.43 ± 0.37 and 5.98 ± 0.00 for nanoemulsions and nanocapsules, respectively. The oil content after preparation was 96%. The inclusion of tea tree oil in nanocapsules showed higher protection against volatilization. The analysis of mean size and polydispersity index of formulations presented no significant alteration during the storage time.

Determinação de peróxido de hidrogênio em antisséptico bucal usando um microdispositivo contendo partículas de Azul da Prússia

A simple flow-injection amperometric procedure using a three-electrode-integrated sensor for the determination of H2O2 in antiseptic mouthwash is reported. This method involves the use of a working composite electrode modified with Prussian Blue (PB) particles that was easily adapted as detector in FIA. The best amperometric response was observed for a composite containing 30% of graphite modified with PB particles (GAP) and 70% of pure graphite (GR). The proposed method presents a linear response in the range of 10 to 200 μmol L-1. The detection and quantification limits were 0.8 and 2.6 μmol L-1, respectively.

Análise térmica aplicada a fármacos e formulações farmacêuticas na indústria farmacêutica

Several matters of the pharmaceutical demonstrate the great importance of thermal analysis application, especially TG and DSC for the pharmaceutical industry future, namely: characterization of the drugs with the thermal events definition, in studies of drug purity, in the polymorphs identification, in compatibility studies of solid dosage pharmaceutical formulations, in drugs and pharmaceutical formulations thermal stability, and in determination of shelf life for isothermal degradation kinetics by extrapolation using the Arrhenius equation. Thus, the test results obtained from thermal analysis are directly related to the quality of a pharmaceutical product, whether the stability or bioavailability of the pharmaceutical product.