An Intravenous Pharmacokinetic Study of Cannabidiol Solutions in Piglets through the Application of a Validated Ultra-High-Pressure Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for the Simultaneous Quantification of CBD and Its Carboxylated Metabolite in Plasma.

Cannabidiol (CBD) has multiple therapeutic benefits that need to be maximized by optimizing its bioavailability. Numerous formulations are therefore being developed and their pharmacokinetics need to be studied, requiring analytical methods and data from intravenous administration. As CBD is susceptible to hepatic metabolism, the requirement of any method is to quantify metabolites such as 7-COOH-CBD.

Relationship between Pharmacokinetic Profile and Clinical Efficacy Data of Three Different Forms of Locally Applied Flurbiprofen in the Mouth/Throat.

This study aimed to link pharmacokinetic (PK) data from different flurbiprofen preparations for the treatment of sore throat with published data to elucidate whether early efficacy is due to the local action of flurbiprofen or a systemic effect after absorption of the swallowed drug. Three comparative bioavailability studies conducted in healthy subjects provided data from flurbiprofen 8.75 mg formulations, including spray solution, spray gel, lozenges, and granules.

In vitro release test (IVRT): Principles and applications.

In vitro drug release test has become one of the most important tools for drug development and approval process of semisolid dosage forms. In vitro release test (IVRT) has the ability to reflect the combined effects of several physicochemical characteristics, particle or droplet size, viscosity, microstructure arrangement of the matter and state of aggregation of dosage form. Genesis of IVRT, its principles and rank order relationship with pharmacodynamic response such as vasoconstriction or dermatopharmacokinetic (skin stripping) results and the evolution of test requirements for regulatory approval is discussed.

Are European marketed acyclovir 5% cream products similar? Comparison with EU and US reference product.

Objective: The aim was to perform a comparative evaluation of composition and release performance of multisource acyclovir 5% creams.

Significance: The outcome was analyzed in relation with the principles of the Topical drug Classification System (TCS).

Methods: The drug release testing (IVRT) was based on selection of an inert artificial membrane and a medium providing sink conditions, and utilizing the vertical diffusion cells.

Rheological and release measurements of manufactured acyclovir 5% creams: confirming sensitivity of the release.

Previous evaluation of marketed acyclovir 5% creams using release testing (IVRT) and its correlation with the qualitative composition confirmed the discriminative characteristics of this methodology. This was in line with the principles of Topical drug Classification System (TCS). For the current research, experimental formulations were designed and prepared by applying controlled changes in manufacturing process, sources of raw materials, and amount of the excipients.

Electrochemical Skin Conductance and Quantitative Sensory Testing on Fibromyalgia.

Background: An impairment of the peripheral nervous system has been suggested in fibromyalgia (FM). Noninvasive distal electrochemical skin conductance (ESC) has been studied little so far when combined with quantitative sensory testing (QST) in patients with FM.

Methods: This study (clinicaltrials.

Effect of procyanidin on dietary iron absorption in hereditary hemochromatosis and in dysmetabolic iron overload syndrome: A crossover double-blind randomized controlled trial.

Background & Aims: Type I hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) are the two most prevalent iron overload diseases. Although many food components, particularly polyphenols, reduce iron bioavailability, there is no clinically validated nutritional strategy to reduce food-iron absorption in patients with these diseases. We aimed to determine whether supplementation with 100 mg of procyanidins during a meal reduces dietary iron absorption in patients with HH or DIOS.

Time Scaling for In Vitro-In Vivo Correlation: the Inverse Release Function (IRF) Approach.

In vitro-in vivo correlations (IVIVC) are methods used to create a link between biopharmaceutical properties such as dissolution and physiological response such as plasma concentration. Level A IVIVC defines 1:1 relationship between the percent absorbed in vivo and the percent dissolved in vitro. A successful level A IVIVC provides the capacity to predict in vivo behavior based only on in vitro data with application in formulation development and support of biowaivers recognized by regulatory agencies across the world.

Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study.

Introduction: Fibromyalgia is characterized by widespread and chronic pain, and its prevalence is increasing worldwide. Milnacipran, an antidepressant, is often prescribed for fibromyalgia with a possible beneficial effect on central pain modulation. The aim of this study was to evaluate if milnacipran could modify the status of conditioned pain modulation (CPM) in patients suffering from fibromyalgia.

Comparative phase I randomized open-label pilot clinical trial of Gynophilus (Lcr regenerans) immediate release capsules versus slow release muco-adhesive tablets.

Gynophilus (Lcr regenerans) is a live biotherapeutic product (LBP) that contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35, which is indicated to restore vaginal health. The aim of the study was to compare the safety, ease of use, and compliance of two formulations (immediate release: IR capsule and slow release: SR muco-adhesive tablets) as well as the colonization of Lcr35 in healthy women. This phase I study (Comprigel) is a parallel, randomized, 4-arm, and open-label clinical trial evaluating an IR daily capsule formulation vs.

An Advanced Formulation of a Magnesium Dietary Supplement Adapted for a Long-Term Use Supplementation Improves Magnesium Bioavailability: In Vitro and Clinical Comparative Studies.

While general recommendations are for 300-mg magnesium intake a day, an advanced low-dose formulation of magnesium chloride, ChronoMag®, was designed to provide 100 mg of magnesium element, thus decreasing the risk of gastrointestinal side effects and allowing long-term supplementation in health conditions related to low magnesium levels. The present study aimed to compare magnesium release profile and bioavailability between this patented low-dose continuous-release magnesium chloride tablet (100 mg magnesium element) and a reference tablet at the usually prescribed dose (300 mg magnesium element). Magnesium release profile was determined by dissolving the tablets in solutions simulating the gastrointestinal tract environment.

In vivo release of peptide-loaded PLGA microspheres assessed through deconvolution coupled with mechanistic approach.

In this study, a reevaluation of the in vivo release phases from long-release PLGA-based microspheres is presented, leading to a better characterization of the plasma concentrations/time profile. Microspheres were designed for intramuscular injection releasing a cyclic somatostatin analog over 70 days. Clinical study was performed in 64 healthy subjects receiving a subcutaneous dose of an immediate release solution as reference formulation and an intramuscular injection of microspheres as test formulation.

Study of the influence of coating methods on lipid spheres manufactured on rotor fluidized bed process.

Different previous works have shown that various kinds of spheres can be manufactured by rotor granulation in a 'single-pot process' using a lipid base: hydrogenated castor oil. This single-pot technology is based on wet granulation where all components are placed in the powder form in the rotor bowl; then, they are continuously suspended in a fluidized air, with a tangentially sprayed liquid solution. This process allows the granulation and manufacturing of sphere during the same time.

Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized, Double-Blind, Placebo-Controlled Study.

The antioxidant, anti-inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double-blind, placebo-controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3-month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty-five subjects (56.

BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements.

The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies. In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing how to meet criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs. Subsequently, the World Health Organization (WHO) and European Medicines Agency (EMA) published guidelines recommending how to obtain BCS biowaivers for BCS Class III drugs (high solubility, low permeability), in addition to Class I drugs.

A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study.

Occasional rhinitis symptoms caused by exposure to pollution or allergens is a growing concern. Based first on empirical observation of a lesser occurrence of allergies in quail farmers and then scientific works on ovomucoids properties, we developed a dietary supplement for the relief of such occasional rhinitis symptoms. The objective of the study was to determine whether one acute oral dose of the study product attenuates nasal provocation and other allergy-related symptoms after exposure to a standardized allergenic challenge as compared to placebo.

Use of domperidone as a galactagogue drug: a systematic review of the benefit-risk ratio.

Breastfeeding is the optimal method for feeding a newborn. However, some mothers may have difficulties lactating. Domperidone is widely used as a galactagogue but to the best of our knowledge has not been approved by any health authority.

Micelle dynamic simulation and physicochemical characterization of biorelevant media to reflect gastrointestinal environment in fasted and fed states.

The characterization of biorelevant media simulating the upper part of the gastrointestinal tract in the fasted and fed states was investigated by classical determination of physicochemical parameters such as pH, osmolality, surface tension and results were compared to in vivo physiological data. Incorporation of fatty material, in order to better simulate the influence of high fat meal was also performed. Stability and characterization of this medium was studied and compared to classical FeSSIF.

Three-stage continuous culture system with a self-generated anaerobia to study the regionalized metabolism of the human gut microbiota.

The technical and ethical difficulties in studying the gut microbiota in vivo warrant the development and improvement of in vitro systems able to simulate and control the physicochemical factors of the gut biology. Moreover, the functional regionalization of this organ implies a model simulating these differences. Here we propose an improved and alternative three-stage continuous bioreactor called 3S-ECSIM (three-stage Environmental Control System for Intestinal Microbiota) to study the human large intestine.

Efficacy of mucoadhesive hydrogel microparticles of whey protein and alginate for oral insulin delivery.

Purpose: To evaluate the efficacy of mucoadhesive insulin-loaded whey protein (WP) /alginate (ALG) microparticles (MP) for oral insulin administration.

Methods: Insulin-loaded microparticles (ins-MP) made of whey protein and alginate were prepared by a cold gelation technique and an adsorption method, without adjunction of organic solvent in order to develop a biocompatible vehicle for oral administration of insulin. In vitro characterization, evaluations of ins-MP in excised intestinal tissues and hypoglycaemic effects after intestinal administration in healthy rats were performed

Results: The release properties and swelling behaviors, investigated in different pH buffers, demonstrated a release based on diffusion mechanism following matrix swelling.

Development and in vitro characterization of insulin loaded whey protein and alginate microparticles.

Insulin was encapsulated into microparticles (MP) made of denaturized whey proteins (WP) and alginate (ALG) using an extrusion/cold gelation process with calcium ions. High encapsulation efficiency of 85% was obtained. Influence of insulin on polymeric viscosity and on microparticle behavior was evaluated.

Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study.

Aim: To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture (LCR35) in patients suffering from irritable bowel syndrome (IBS).

Methods: A randomized, double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria. Patients were allocated to receive either LCR35 (n = 25) at a minimum daily dose of 6 × 10(8) colony forming units or placebo (n = 25) for 4 wk.

Cisplatin pharmacokinetics in nontumoral pig liver treated with intravenous or transarterial hepatic chemoembolization.

Purpose: To evaluate cisplatin (CDDP) pharmacokinetics after its intravenous (IV) or intrahepatic arterial administration (IHA) in healthy pigs with or without embolization by absorbable gelatine.

Material And Methods: We analysed plasmatic and hepatic drug concentration in four groups of six mini-pigs each according to the modality of administration of CDDP (1 mg/kg): IV, IHA, IHA with partial embolization using absorbable gelatine (IHA-Pe), and IHA with complete embolization (IHA-Te). Unbounded plasmatic and hepatic platinum concentrations were measured.