Identification and Characterization of Rotigotine Degradation Products by HPLC Coupled DAD and CAD Detectors and HRMS Through Q-Orbitrap and Electrospray Ionization.

Rotigotine (RTG) is a dopamine agonist used in the treatment of Parkinson's disease. As it is susceptible to oxidation, stability studies must be carefully designed for the identification and characterization of all possible degradation products. Here, RTG degradation was evaluated according to the International Conference on Harmonization guidelines under various stress conditions, including acidic and basic hydrolysis, oxidative, metallic, photolytic, and thermal conditions.

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of infection in BALB/c mice.

Use of Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach.

Background: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability.

Objective: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems.

Methods: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied.

Alternative Methods for Pulmonary-Administered Drugs Metabolism: A Breath of Change.

Prediction of pulmonary metabolites following inhalation of a locally acting pulmonary drug is essential to the successful development of novel inhaled medicines. The lungs present metabolic enzymes, therefore they influence drug disposal and toxicity. The present review provides an overview of alternative methods to evaluate the pulmonary metabolism for the safety and efficacy of pulmonary delivery systems.

Development of rivaroxaban microemulsion-based hydrogel for transdermal treatment and prevention of venous thromboembolism.

We have developed a microemulsion (ME)-based hydrogel, containing propylene glycol, Azone®, Labrasol®, isobutanol and water (20:3:18:3:56), for the transdermal delivery of rivaroxaban (RVX). Formulation ME-1:RVX, which was loaded with 0.3 mg/g of RVX, presented as a clear, homogenous fluid with a droplet size of 82.

Lopinavir/Ritonavir: A Review of Analytical Methodologies for the Drug Substances, Pharmaceutical Formulations and Biological Matrices.

Lopinavir/ritonavir is a potent coformulation of protease inhibitors used against HIV infection. Lopinavir is the main responsible for viral load suppression, whereas ritonavir is a pharmacokinetic enhancer. Both of them have recently gained relevance as candidate drugs against severe coronavirus disease (COVID-19).

Clofazimine functionalized polymeric nanoparticles for brain delivery in the tuberculosis treatment.

Central nervous system tuberculosis (CNS-TB) is the most severe form of the disease especially due to the inability of therapeutics to cross the blood-brain barrier (BBB). Clofazimine (CFZ) stands out for presenting high in vitro activity against multi-drug resistant strains of Mycobacterium tuberculosis, however, CFZ physicochemical and pharmacokinetics properties limit drug penetration into the CNS and, consequently, its clinical use. The aim of this work was to develop polymeric nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) loaded with CFZ and functionalized with a transferrin receptor (TfR)-binding peptide, aiming brain drug delivery for CNS-TB treatment by the intravenous route.

Stability Indicating Methods for Determination of Third Generation Antiepileptic Drugs and Their Related Substances.

The third generation of antiepileptic drugs that have been approved by international regulatory agencies between 2007 and 2018 include rufinamide, stiripentol, eslicarbazepine acetate, lacosamide, perampanel, brivaracetam and everolimus. As part of demonstrating their safety profile, stability indicating methods are developed to monitor these drugs and their impurities. In this context, this review describe some characteristics, impurities and the stability indicating methods used for the determination of these drugs and the presence of their related substances.

Ezetimibe: A Review of Analytical Methods for the Drug Substance, Pharmaceutical Formulations and Biological Matrices.

Ezetimibe (EZM) is a selective inhibitor of the sterol transporter Niemann-Pick C1-Like 1 in the small intestine used as an adjunctive therapy to lower cholesterol levels in cases of hyperlipidemia. The goal of this work was to summarize the main physical-chemical, pharmacological and pharmacokinetic characteristics of EZM, as well as to describe the main analytical methodologies for the quantification of the drug. Methods described in the United States Pharmacopeia for EZM raw material and tablets were also presented.

Rotigotine: A Review of Analytical Methods for the Raw Material, Pharmaceutical Formulations, and Its Impurities.

Background: Rotigotine is a dopaminergic agonist developed for the treatment of Parkinson's disease and restless leg syndrome. The pure levorotatory enantiomer is marketed in several countries as a transdermal patch. Reports of oxidation and instability in a previous formulation indicate the need to evaluate impurities in both the raw material and pharmaceutical dosage forms of rotigotine to ensure product quality.

Effects of a novel roflumilast and formoterol fumarate dry powder inhaler formulation in experimental allergic asthma.

In this study we aimed to develop a roflumilast (R) and formoterol fumarate (F) dry powder inhaler formulation (DPI) incorporating HPβCD by spray drying and evaluated if it attenuates the inflammatory process and improves lung function in a murine model of ovalbumin induced allergic asthma. The DPI was characterized by powder X-ray diffraction, thermal analysis, scanning electron microscopy, particle size, density, specific surface area and dynamic vapor sorption analyses. In vitro deposition studies were performed using a NGI, while transepithelial permeability and in vivo effects on lung mechanics and inflammation in a model of allergic asthma were also assessed.

In Vitro-In Vivo Correlation for Desvenlafaxine Succinate Monohydrate Extended Release Tablets.

The objective of this study was to develop a dissolution test in order to establish an in vitro-in vivo correlation (IVIVC) model for desvenlafaxine succinate monohydrate (DVSM) extended release (ER) tablets. The in vitro release characteristics of the drug were determined using USP apparatus 1 at 75 rpm, with volume of HCl pH 1.2, acetate buffer solution (ABS) pH 4.

Nanoparticles Loaded with a New Thiourea Derivative: Development and Evaluation Against .

Background: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus . Current treatments are restricted to a small number of drugs that display both severe side effects and a potential for parasites to develop resistance. A new -(3,4-methylenedioxyphenyl)-'- (2-phenethyl) thiourea compound (thiourea 1) has shown promising activity against with an IC of 54.

Vancomycin-loaded nanoparticles against vancomycin intermediate and methicillin resistant Staphylococcus aureus strains.

Bacterial infections represent one of the leading causes of mortality in the world. Among causative pathogens, S. aureus is prominently known as the underlying cause of many multidrug resistant infections that are often treated with the first-line choice antibiotic vancomycin (VCM).

Development of a liquid chromatography Q Exactive high resolution mass spectrometry method by the Box-Behnken design for the investigation of sibutramine urinary metabolites.

Sibutramine is cited by the World Anti-Doping Agency as a stimulant. According to the literature, sibutramine is extensively metabolized into N-desmethyl-sibutramine (M1), N-bisdesmethyl-sibutramine (M2) and monohydroxy derivatives of M1 and M2. Therefore, it is important to verify new sibutramine metabolites through current analytical methodologies, such as liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS).

Development of USP Apparatus 3 Dissolution Method with IVIVC for Extended Release Tablets of Metformin Hydrochloride and Development of a Generic Formulation.

Metformin is a euglycemic drug for the treatment of type 2 diabetes mellitus. To date, there are 13 dissolution methodologies described in the U.S.

Sensitive detection of topiramate degradation products by high-performance liquid chromatography/electrospray ionization mass spectrometry using ion-pairing reagents and polarity switching.

Rationale: The chromatographic analysis of topiramate and its degradation products is challenging due to the absence of chromophoric moieties in their structures, the wide polarity range of the compounds and their ionization differences. This work proposes two new mass spectrometry approaches for evaluating these analytes.

Methods: Based on the calculated experimental limit of detection (LOD), a highly sensitive high-performance liquid chromatography (HPLC) paired-ion electrospray ionization mass spectrometry (PIESI-MS) method was developed for the determination of topiramate inorganic degradation products.

Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges.

Zebrafish (Danio rerio) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four model compounds. Sibutramine was applied for the multivariate optimization of ZWT conditions, also for the comparison of the metabolism among ZWT, humans and mice, beyond for the role of CYP2B6 in ZWT. After the optimization, 18 fish and 168 hours of experiments is the minimum requirement for a relevant panel of biotransformation products.

Development of a new formulation of roflumilast for pulmonary drug delivery to treat inflammatory lung conditions.

The aim of this study was to develop roflumilast dry powder inhaler (DPI) formulations by spray drying using hydroxypropyl-β-cyclodextrin (HPβCD) and to determine their suitability for pulmonary delivery. Different feed solution concentrations, solvent systems and spray drying parameters were used to obtain the formulations which were characterized using X-ray powder diffraction, thermal analysis, scanning electron microscopy, particle size distribution, bulk and tapped density, specific surface area, dynamic vapour sorption, in vitro deposition properties using a Next Generation Impactor (NGI) and transepithelial permeability. Microparticles spray dried from ethanol were wrinkled and amorphous, exhibiting high glass transition temperatures while those from methanol:n-butyl acetate consisted of irregularly shaped porous particles partially crystalline.

Blueberry Residue Encapsulation by Ionotropic Gelation.

In the processing of fruits such as blueberry (Vaccinium sp), that has high levels of phenolic acid, the food industry produces tons of organic waste that causes harm to the environment. Encapsulation is a technique used to take advantage of these wastes. Several methods are used to encapsulate substances, among them ionotropic gelation proves to be a simple, precise, efficient and economical method for obtaining particles with encapsulated bioactives.

Zebrafish (Danio rerio): A valuable tool for predicting the metabolism of xenobiotics in humans?

Zebrafish has become a popular model organism in several lines of biological research sharing physiological, morphological and histological similarities with mammals. In fact, many human cytochrome P450 (CYP) enzymes have direct orthologs in zebrafish, suggesting that zebrafish xenobiotic metabolic profiles may be similar to those in mammals. The focus of the review is to analyse the studies that have evaluated the metabolite production in zebrafish over the years, either of the drugs themselves or xenobiotics in general (environmental pollutants, natural products, etc.

Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods.

In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying.

Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using USP Apparatus 3 with in Vitro-in Vivo Correlation.

Gliclazide (GLZ) is a second generation hypoglycemic drug used for the treatment of Type 2 diabetes mellitus. The low solubility of GLZ has been described as the rate limiting step for drug dissolution and absorption, thus a prediction of its in vivo behavior based on a discriminative dissolution test should lead to a relevant in vitro-in vivo correlation (IVIVC). The aim of this study was to develop a dissolution method for GLZ modified-release (MR) tablets using an United States Pharmacopeia (USP) apparatus 3 through its evaluation by an IVIVC analysis.

A promising oral fucoidan-based antithrombotic nanosystem: Development, activity and safety.

Fucoidan-loaded nanoparticles emerge as great candidates to oral anticoagulant therapy, due to increasing of bioavailability and circulation time of this natural anticoagulant. Crosslink between chitosan chains are performed using glutaraldehyde to confer higher gastric pH resistance to nanoparticle matrices. In this work, chitosan-fucoidan nanoparticles, without (NpCF) and with glutaraldehyde crosslink (NpCF 1% and NpCF 2%), were prepared to evaluate their anticoagulant, antithrombotic and hemorrhagic profile.

Development and validation of a stability-indicating HPLC method for topiramate using a mixed-mode column and charged aerosol detector.

The analysis of topiramate in the presence of its main degradation products is challenging due to the absence of chromophore moieties and their wide range of polarity. Mixed-mode chromatography has been used in such cases because it combines two or more modes of separation. Charged aerosol detector is also an alternative since its detection is independent of optical properties and analyte ionization.