The pharmaceutical applications of a biopolymer isolated from seeds: Focus on the freeze-dried matrix forming capacity.

The aim of the present study was to evaluate the funtion of fenugreek seed mucilage (FSM) as potential matrix forming agent for orodispersible pharmaceutical lyophilisates. The FSM was isolated and characterized. FSM colloidal dispersions were prepared and the rheological evaluation was performed.

Development of oral lyophilisates containing meloxicam nanocrystals using QbD approach.

The aim of this study was to develop oral lyophilisates with improved meloxicam (MEL) dissolution, optimizing each step of the preparation by design of experiments. First, meloxicam nanosuspensions were prepared by high-pressure homogenization (HPH), using PVP, Poloxamer or PEG as stabilizers and were subjected to freeze-drying using mannitol as cryoprotectant. The effects of the stabilizers and cryoprotectant were assessed and an optimal formulation was generated within the Design Space where the particle sizes and the PDIs are at their lowest values.

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system.

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE.

Development of a reservoir type prolonged release system with felodipine via simplex methodology.

Background And Aims: Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method.

Methods: The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release.

Optimization of the sonication process for meloxicam nanocrystals preparation.

Background And Aims: Meloxicam, a widely recommended AINS, presents poor water solubility, which limits its bioavailability and effect onset. The objective of this study is the investigation of the most important factors that influence the efficiency of sonication in the preparation of meloxicam nanocrystals.

Methods: The effects of crucial technological sonication parameters (amplitude, time and applied cycle) on the crystal sizes and dissolution were investigated using a central composite experimental design with three factors and three levels.

Investigation into the role of Cu/Zn-SOD delivery system on its antioxidant and antiinflammatory activity in rat model of peritonitis.

Background: The current study evaluated the role of delivery system (solution, conventional liposomes and PEG-ylated liposomes) on superoxide dismutase (SOD) antioxidant and antiinflammatory properties in a rat model of lipopolysaccharide (LPS)-induced peritonitis.

Methods: Fifty male albino rats (Wistar-Bratislava) were divided into five groups (n=10). Control group received saline and the other four groups received intraperitoneal injections of LPS (5mg/kg).

Selecting oral bioavailability enhancing formulations during drug discovery and development.

Introduction: The role of chemical structure, lipophilicity, physico-chemical, absorption, distribution, metabolism, excretion, toxicity (ADMET) and biopharmaceutical properties of compounds including bioavailability are critical in drug discovery and drug dosage forms design.

Areas Covered: The authors discuss a number of parameters including computational approaches used for selected chemical structures with biological activity for lead optimization and chemogenomics and preclinical studies for ADMET process development of ligand properties. The authors also look at a number of other parameters including: early drug product formulations with method selection based on the biopharmaceutical classification system (BCS); in vitro-in vivo correlation (IVIVC) and different formulation strategies to enhance solubility; dissolution rate and permeability; bioavailability evaluation and quality by design as an opportunity to develop 'safe space' regions, where bioavailability is unaffected by pharmaceutical variations.

Subcellular drug targeting, pharmacokinetics and bioavailability.

Effective treatment of diseases at the molecular level is possible by directing the drug substance (micromolecular, protein or peptide drugs, DNA, oligonucleotides, siRNA) with the aid of a specialized nanoparticulate carrier, for safe and effective transport to the specific site of action in the cytosol and its organelles including nuclear targeting. To achieve efficient cytosolic delivery of therapeutics or nuclear targeting, different drug delivery systems (DDS) have been developed (macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers) capable of subcellular internalization overcoming the biological barriers, by passive targeting and especially by active targeting (receptor-targeted delivery). The success depends on the physicochemical nature of DDS, intracellular barriers that these systems need to overcome, the bioavailability of the bioactive drug, biodistribution, the intracellular pharmacokinetics and its influence on the pharmacodynamic effect.

Quantification of ascorbic acid and sodium ascorbate in powder blends for tableting and in vitamin C chewable tablets by NIR-chemometry.

The paper proposes a near infrared method able to directly and simultaneously quantify ascorbic acid and sodium ascorbate in powder blends for tableting and in vitamin C chewable tablets without any sample preparation. In the first step, calibration models for the quantification of ascorbic acid and sodium ascorbate in powder blends for tableting and subsequently in chewable vitamin C tablets (corresponding to 80-120 % active substance) were developed according to an experimental design with 2 variables and 5 levels. Then, using the best calibration models, the methods were fully validated in terms of recovery, precision and accuracy for both powder blends and vitamin C chewable tablets.

Systemic and biophase bioavailability and pharmacokinetics of nanoparticulate drug delivery systems.

The development of the vectorized delivery systems combining advantages of the colloidal carriers, with active targeting to the receptors sites suggests that nanoparticles have a considerable potential for treatment after biophase internalization and pharmacokinetics, as for example gene therapy. Two major mechanisms can be distinguished for addressing the desired sites for drug release: (i) passive and (ii) active targeting. Examples of passive targeting were presented: organ targeting by the Enhanced Permeability and Retention (EPR) effect; targeting the mononuclear phagocitic system; organ targeting by chemoembolization or local (organ) administration;sterical stabilization of nanoparticles (PEGylation).

Development and in vitro evaluation of multiparticulate sustained release carbamazepine formulation.

The objective of the present study was the development and the in vitro evaluation of extended release multiparticulate dosage forms with carbamazepine, starting from drug crystals of established granulometry as cores and using Eudragit NE aqueous dispersions as coating film polymer in a bottom spray fluid bed coating system. The chosen independent variables, i.e.

Drug delivery systems with modified release for systemic and biophase bioavailability.

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body.

Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects.

Background: Phenytoin is an inductor of the main metabolizing enzyme of ivabradine and it could influence its pharmacokinetics. Changes in ivabradine pharmacokinetics could have clinical significance regarding the safety of the treatment.

Objective: The study objective was evaluation of the pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects.

Simultaneous quantification of l-α-phosphatidylcholine and cholesterol in liposomes using near infrared spectrometry and chemometry.

This paper describes the development and validation of a multivariate method based on transmittance NIR spectroscopy for simultaneous quantification of l-α-phosphatidylcholine (LPC) and cholesterol (CHO). Method development was based on a D-optimal experimental design consisting of 16 LPC-CHO mixtures. Calibration models were generated by partial least-squares (PLS) and principal component regression (PCR) method followed by leave-one-out cross-validation.

High-Throughput NIR-Chemometric Method for Meloxicam Assay from Powder Blends for Tableting.

A near infrared (NIR) method able to directly quantify the active content in pharmaceutical powder blends used for manufacturing meloxicam tablets, without any sample preparation, was developed and fully validated. To develop calibration models for the assay of meloxicam in powder blends for tableting, the NIR reflectance spectra of different meloxicam powder blends prepared according to a calibration protocol was analysed using different preprocessing methods by partial last-square regression (PLS) and principal component regression (PCR).The best calibration model was found when partial last-square regression (PLS) was used as regression algorithm in association with Smoothing-Savitsky as pre-processing spectrum method.

Effect of fluvoxamine on the pharmokinetics of zolpidem: a two-treatment period study in healthy volunteers.

1. Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and fluvoxamine in healthy volunteers. 2.

Effect of fluoxetine on the pharmacokinetics of lansoprazole: a two-treatment period study in healthy male subjects.

Background: Fluoxetine is an inhibitor of the main metabolizing enzymes of lansoprazole and could influence the pharmacokinetics of lansoprazole. The changes in lansoprazole pharmacokinetics could have clinical significance concerning the safety of the therapy.

Objective: The aim of this study was to evaluate the pharmacokinetic interaction between fluoxetine and lansoprazole in healthy subjects.

Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers.

Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers. The study consisted of two periods: Period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem and Period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 500 mg ciprofloxacin. Between the two periods, the subjects were treated for 5 days with a single daily dose of 500 mg ciprofloxacin.

Pharmacokinetics and comparative bioavailability of two fenofibrate capsule formulations in healthy volunteers.

The objective of this study was to evaluate the pharmacokinetics of fenofibric acid, the main metabolite of fenofibrate (CAS 49562-28-9), and to assess the average bioequivalence of two immediate release formulations of 200 mg fenofibrate capsules in 24 healthy volunteers. The relative bioavailability of the test (generic) product Lipivim with respect to the reference product was determined in a single dose, randomized, crossover study. Only the concentrations of fenofibric acid could be used for bioequivalence determination, because the concentrations of the parent drug were too low to be accurately measured in the biological matrix.

Pharmacokinetic interaction between fluoxetine and omeprazole in healthy male volunteers: a prospective pilot study.

Background: Fluoxetine is an inhibitor of the main metabolizing enzymes (cytochrome P450 [CYP] 2C19 and CYP3A4) of omeprazole and thus might influence that drug's pharmacokinetics. The changes in omeprazole's pharmacokinetics may have clinical significance concerning efficacy and tolerability of the treatment.

Objective: The aim of this study was to assess the pharmacokinetic interaction of fluoxetine with omeprazole in healthy volunteers.

Pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers.

The objective of this study was to evaluate the pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers. The study consisted of 2 periods: period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem, and period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 400 mg carbamazepine. Between the 2 periods, the participants were treated for 15 days with a single daily dose of 400 mg carbamazepine.

Nanotechnology for delivery of drugs and biomedical applications.

Nanotechnology is a multidisciplinary scientific field that deals with the formulation, preparation, characterization and application of structures, devices and systems at nanometric scale. Area of concern is interdisciplinary, but with peculiarities, among others, medicine, pharmacy, biophysics, electronics, bioengineering, and molecular biology. Interest for modern nanotechnology lies in the creation and use of structures which have new properties because of their small size as well as the possibility of using these systems to control or manipulate biological structures at nanometric or atomic level.

Rapid high-performance liquid chromatography-tandem mass spectrometry method for determination of pentoxifylline and its active metabolites M1 and M5 in human plasma and its application in bioavailability study.

A new rapid, sensitive and selective liquid chromatography coupled with mass spectrometry method was developed and validated for the simultaneous quantification of pentoxifylline (PTX) and two major active metabolites in human plasma (M1 and M5). After a deproteinization step, chromatographic separation of the selected analytes was performed on a RP-C18 column. The detection of target compounds was in multiple reaction monitoring mode using an ion trap mass spectrometer equipped with an electrospray ion source.

Influence of dextran on the bioadhesive properties of poly(anhydride) nanoparticles.

This work describes the bioadhesive properties of poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN) nanoparticles (NP) associated with various types of dextran (two hydroxyl-functionalized dextrans and one amino-derivative of dextran). The association of dextran to the polymer was performed either prior NP formation or by the attachment of dextran to the surface of the just formed NP. The amount of dextran associated to the nanoparticles was quantified by a HPLC/ELSD method and dextran presence in the nanoparticles was confirmed by IR spectroscopy, (1)H NMR and in vitro agglutination assay.