Determination of Quinine and Doxycycline in Rat Plasma by LC�CMS�CMS: Application to a Pharmacokinetic Study

A fast, sensitive, and specific LC?CMS?CMS method for determination of quinine (QN) and doxycycline (DOX) in rat plasma has been developed and validated. QN, DOX, and cimetidine (internal standard, IS) were extracted from the plasma by protein precipitation. The compounds were separated on a C₁₈ column with methanol?C0.1% aqueous formic acid 70:30 (v/v) as mobile phase at a flow rate of 0.5 mL min^?1 (split 1:3). Detection was by positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, monitoring the transitions 325.0 ?? 307.0, 445.0 ?? 428.1, and 252.8 ?? 159.0, for QN, DOX, and IS, respectively. The analysis was carried out in 2.0 min and the method was linear in the plasma concentration range 5?C5,000 ng mL^?1. The mean extraction recoveries for QN, DOX, and IS from plasma were 89.4, 90.5, and 86.3%, respectively. The method was validated for linearity, precision, accuracy, specificity, and stability; the results obtained were within the acceptable range. The proposed method was successfully applied to the determination of QN and DOX in rat plasma samples to support pharmacokinetic studies.     

Simultaneous determination of Al(III) and Fe(III) in post-hemodialysis fluids by spectrophotometry and multivariate calibration

A multivariate calibration model (PLS) was developed for the simultaneous spectrophotometric determination of Al(III) and Fe(III) in post-hemodialysis fluids with pyrocathecol violet (PCV) as chromogenic reagent. The analytes build stable complexes with PCV in presence of hexamine buffered medium at pH 6.1. The complexes show overlapped absorption bands in the spectral range of 220-800 nm so that absorptions of 580 wavelengths were necessary for the calibrations. Determinations of Al(III) and Fe(III) were done without masking agents. The best calibration model was obtained by using PLS-1 regression with three components after data mean centering. The spectrophotometric method applied to assay the analytes in real post-hemodialysis samples containing no desferrioxamine B presented good agreement with voltammetric measurements used as reference. Concentrations ranging from 0.20 to 0.60 mg L⁻¹ for Al(III) and for Fe(III) were determined in real samples. The multivariate detection limits for Al(III) and Fe(III) were 0.044 and 0.052 mg L⁻¹, respectively, and the calculated values of sensitivity were 6.33 for Al(III) and 3.44 for Fe(III). The proposed method showed to be straightforward and useful to follow the hemodialysis progress for patients under treatment. Interferents were also investigated.     

Redispersible spray-dried nanocapsules for the development of skin delivery systems: proposing a novel blend of drying adjuvants

This study proposes a novel blend of drying adjuvants (lactose and polyvinylpyrrolidone) as an approach to produce dispersible powders containing nanocapsules for the development of skin delivery systems. Hydrogels were produced with liquid nanocapsules and spray-dried powders. Nanoparticle recovery was obtained after powder aqueous redispersion. No influence of the intermediate product was observed on the hydrogel properties and on the drug release profile. The novel blend of drying adjuvants is a smart approach to obtain dried nanocapsules with excellent aqueous redispersion and to maintain the drug release profile of the original suspension in the design of novel skin delivery systems.     

A study of physicochemical and biopharmaceutical properties of amoxicillin tablets using full factorial design and PCA biplot

The variables that influence the tablets obtained by direct compression method deserve to be studied to minimize formulations costs and to improve the physicochemical and biopharmaceutical properties of the compacts. Here, we explore the adjuvants effects on amoxicillin tablet formulations considering multiple responses, and indicate the most suitable formulation composition. A 2(3) full factorial design was built to different amoxicillin formulations, each one containing three replicate batches, and eight responses (physicochemical and biopharmaceutical parameters) were obtained. The microcrystalline cellulose (MCC) type Avicel PH-102 (low) or PH-200 (high), the absence (low) or presence (high) of spray-dried lactose (LAC), and the absence (low) or presence (high) of disintegrant (DIS) were the levels investigated. The more relevant responses to the distinct formulations from the experimental design were hardness, friability, and the amount of amoxicillin dissolved during the first hour. PCA biplot indicated high values of amount of drug dissolved in 60 min as advantageous responses for the investigated amoxicillin tablet formulations and high values of friability as not desirable. Considering the individual response evaluation, the most suitable amoxicillin tablet formulation should present in its composition the MCC type Avicel PH-102 (low level) and the superdisintegrant agent (DIS high level), croscarmellose sodium, but no LAC (low level).     

Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development,Characterization and Applications

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.