Natural Antimicrobial Compounds as Promising Preservatives: A Look at an Old Problem from New Perspectives.

Antimicrobial compounds of natural origin are of interest because of the large number of reports regarding the harmfulness of food preservatives. These natural products can be derived from plants, animal sources, microorganisms, algae, or mushrooms. The aim of this review is to consider known antimicrobials of natural origin and the mechanisms of their action, antimicrobial photodynamic technology, and ultrasound for disinfection.

Erectile Dysfunction Therapy of Bariatric Patients: Tadalafil Biopharmaceutics and Pharmacokinetics Before vs. After Gastric Sleeve/Bypass.

Bariatric surgery introduces significant changes in the gastrointestinal tract, which may affect oral drug absorption/bioavailability. Here we investigate the phosphodiesterase-5 inhibitor (PDE5i) tadalafil for potentially impaired post-bariatric solubility/dissolution and absorption. Solubility was studied in vitro in different pHs, and ex vivo in gastric content aspirated from patients pre/post-surgery.

Quantification of Etoricoxib in Low Plasma Volume by UPLC-PDA and Application to Preclinical Pharmacokinetic Study.

An ultra-performance liquid chromatography with photodiode array (UPLC-PDA) UV detection method was developed here for the first time for simple, rapid, selective and sensitive quantification of the commonly prescribed selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib in low plasma volumes (50 μL). The method includes protein precipitation followed by liquid-liquid extraction, evaporation and reconstitution. A gradient mobile phase of 75:25 going to 55:45 (/) water:acetonitrile (1 mL/min flow rate) was applied.

[IMPACT OF CLINICAL PHARMACIST CONSULTATIONS ON RATE OF COMPLICATIONS, RE-HOSPITALIZATIONS AND MORTALITY IN PATIENTS UNDERGOING BARIATRIC SURGERY].

Background: Patients undergoing bariatric surgery are prone to changes in absorption, improvement in their chronic diseases and other pharmacokinetic/pharmacodynamic alteration which can affect continuation and the required doses of their chronic medications.

Objectives: To examine the effect of a clinical pharmacist's consultation on the rate of complications, re-hospitalizations and mortality among patients who underwent bariatric surgery.

Methods: In this retrospective cohort study, results of bariatric patients who were consulted by a clinical pharmacist between the years 2013-2019 were compared with the results of a wider group of bariatric patients with chronic diseases who were recorded in the Israeli General Bariatric Registry during the same years.

Ethanol-based solubility-enabling oral drug formulation development: Accounting for the solubility-permeability interplay.

The aim of the current work was to investigate the key factors that govern the success/failure of an ethanol-based solubility-enabling oral drug formulation, including the effects of the ethanol on the solubility of the drug, the permeability across the intestinal membrane, the drug's dissolution in the aqueous milieu of the gastrointestinal tract (GIT), and the resulting solubility-permeability interplay. The concentration-dependent effects of ethanol-based vehicles on the solubility, the in-vitro Caco-2 permeability, the in-vivo rat permeability, and the biorelevant dissolution of the BCS class II antiepileptic drug carbamazepine were studied, and a predictive model describing the solubility-permeability relationship was developed. Significant concentration-dependent solubility increase of CBZ was obtained with increasing ethanol levels, that was accompanied by permeability decrease, both in Caco-2 and in rat perfusion studies, demonstrating a tradeoff between the increased solubility afforded by the ethanol and a concomitant permeability decrease.

Can Consultation by a Clinical Pharmacist Prevent Morbidity and Mortality in Patients Undergoing Bariatric Surgery?

The purpose of this work was to investigate the effect of clinical pharmacist consultation on the long-term morbidity and mortality outcomes among patients undergoing bariatric surgery. In this retrospective cohort study, 165 bariatric patients at Herzliya Medical Center who were identified as complex cases and were consulted by a clinical pharmacist (2013-2019) were compared with a wider group of bariatric patients with chronic diseases who were recorded in the Israeli General Bariatric Registry during the same years. The primary outcomes were rates of surgical complications, re-hospitalizations, and death up to one year after surgery.

The Complexity of Bariatric Patient's Pharmacotherapy: Sildenafil Biopharmaceutics and Pharmacokinetics before vs. after Gastric Sleeve/Bypass.

Postbariatric altered gastrointestinal (GI) anatomy/physiology may significantly harm oral drug absorption and overall bioavailability. In this work, sildenafil, the first phosphodiesterase-5 (PDE5) inhibitor, was investigated for impaired postbariatric solubility/dissolution and absorption; this research question is of particular relevance since erectile dysfunction (ED) is associated with higher body mass index (BMI). Sildenafil solubility was determined both in vitro and ex vivo, using pre- vs.

Solubility-enabling formulations for oral delivery of lipophilic drugs: considering the solubility-permeability interplay for accelerated formulation development.

Introduction: Tackling low water solubility of drug candidates is a major challenge in today's pharmaceutics/biopharmaceutics, especially by means of modern solubility-enabling formulations. However, drug absorption from these formulations oftentimes remains unchanged or even decreases, despite substantial solubility enhancement.

Areas Covered: In this article, we overview the simultaneous effects of the formulation on the solubility and the apparent permeability of the drug, and analyze the contribution of this solubility-permeability interplay to the success/failure of the formulation to increase the overall absorption and bioavailability.

An Emerging Strategy for Neuroinflammation Treatment: Combined Cannabidiol and Angiotensin Receptor Blockers Treatments Effectively Inhibit Glial Nitric Oxide Release.

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid found in cannabis, has anti-neuroinflammatory properties. Despite the increasing use of CBD, little is known about its effect in combination with other substances. Combination therapy has been gaining attention recently, aiming to produce more efficient effects.

Towards Effective Antiviral Oral Therapy: Development of a Novel Self-Double Emulsifying Drug Delivery System for Improved Zanamivir Intestinal Permeability.

Self-double emulsifying drug delivery systems have the potential to enhance the intestinal permeability of drugs classified under the Biopharmaceutics Classification System (BCS) class III. One such example is the antiviral agent zanamivir, exhibiting suboptimal oral absorption (with a bioavailability range of 1-5%). To address this challenge, we have developed an innovative oral formulation for zanamivir: a self-double nanoemulsifying Winsor delivery system (SDNE-WDS) consisting of the microemulsion, which subsequently yields final double nanoemulsion (W/O/W) upon interaction with water.

Selective COX-2 inhibitors after bariatric surgery: Celecoxib, etoricoxib and etodolac post-bariatric solubility/dissolution and pharmacokinetics.

Anatomical/physiological gastrointestinal changes after bariatric surgery may influence the fate of orally administered drugs.Since non-selective NSAIDs are not well-tolerated post-surgery, selective cyclooxygenase-2 (COX-2) inhibitors may be important for these patients. In this work we investigated celecoxib, etoricoxib and etodolac, for impaired post-bariatric solubility/dissolution and absorption.

Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In Vitro and In Vivo.

Multiple sclerosis (MS) is a widespread chronic neuroinflammatory and neurodegenerative disease. Microglia play a crucial role in the pathogenesis of MS via the release of cytokines and reactive oxygen species, e.g.

Enabling oral delivery of antiviral drugs: Double emulsion carriers to improve the intestinal absorption of zanamivir.

Antiviral drugs play a major role in the control of seasonal influenza epidemics and may provide prophylactic and therapeutic benefits during an eventual pandemic. Among the neuraminidase inhibitors, zanamivir has been shown to be a potent inhibitor of influenza viruses, and similarly against emerging resistant strains. Despite its high antiviral efficiency, zanamivir suffers from poor intestinal permeability, therefore administered via inhalation.

Carbamazepine Therapy After Bariatric Surgery: Eight Sleeve Gastrectomy Cases and Review of the Literature.

Bariatric surgery modifies the anatomy and physiology of the gastrointestinal tract. Carbamazepine (CBZ) is an anticonvulsant with multiple neuropsychiatric indications. Given CBZ physicochemical properties and narrow therapeutic index, bariatric surgery may potentially introduce clinically significant changes in CBZ oral absorption and bioavailability.

The Role of Paracellular Transport in the Intestinal Absorption and Biopharmaceutical Characterization of Minoxidil.

The purpose of this study was to evaluate mechanisms behind the intestinal permeability of minoxidil, with special emphasis on paracellular transport, and elucidate the suitability of minoxidil to be a reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil (vs. metoprolol) was evaluated in-silico, in-vitro using both the PAMPA assay and across Caco-2 cell monolayers, as well as in-vivo in rats throughout the entire intestine.

Antiallergic Treatment of Bariatric Patients: Potentially Hampered Solubility/Dissolution and Bioavailability of Loratadine, but Not Desloratadine, Post-Bariatric Surgery.

Gastrointestinal anatomical/physiological changes after bariatric surgery influence variables affecting the fate of drugs after ingestion, and medication management of these patients requires a thorough and complex mechanistic analysis. The aim of this research was to study whether loratadine/desloratadine antiallergic treatment of bariatric patients is at risk of being ineffective due to impaired solubility/dissolution. The pH-dependent solubility of loratadine/desloratadine was studied in vitro, as well as ex vivo, in gastric content aspirated from patients before versus after bariatric surgery.

Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation.

Ultra-long-acting integrase strand transfer inhibitors were created by screening a library of monomeric and dimeric dolutegravir (DTG) prodrug nanoformulations. This led to an 18-carbon chain modified ester prodrug nanocrystal (coined NM2DTG) with the potential to sustain yearly dosing. Here, we show that the physiochemical and pharmacokinetic (PK) formulation properties facilitate slow drug release from tissue macrophage depot stores at the muscle injection site and adjacent lymphoid tissues following single parenteral injection.

PLA-Triggered Activation of Cyclosporine-Phospholipid Prodrug as a Drug Targeting Approach in Inflammatory Bowel Disease Therapy.

Oral medication with activity specifically at the inflamed sites throughout the gastrointestinal tract and limited systemic exposure would be a major advance in our therapeutic approach to inflammatory bowel disease (IBD). For this purpose, we have designed a prodrug by linking active drug moiety to phospholipid (PL), the substrate of phospholipase A (PLA). PLA expression and activity is significantly elevated in the inflamed intestinal tissues of IBD patients.

Prodrug-Based Targeting Approach for Inflammatory Bowel Diseases Therapy: Mechanistic Study of Phospholipid-Linker-Cyclosporine PLA-Mediated Activation.

Therapeutics with activity specifically at the inflamed sites throughout the gastrointestinal tract (GIT) would be a major advance in our therapeutic approach to inflammatory bowel disease (IBD). We aimed to develop the prodrug approach that can allow such site-specific drug delivery. Currently, using cyclosporine as a drug of choice in IBD is limited to the most severe cases due to substantial systemic toxicities and narrow therapeutic index of this drug.

Managing the Unpredictable: Mechanistic Analysis and Clinical Recommendations for Lamotrigine Treatment after Bariatric Surgery.

Bariatric surgery may alter the absorption and overall bioavailability of oral drugs. Lamotrigine is a major antiepileptic and mood stabilizer, that its use after bariatric surgery has not yet been studied. In this article, we provide a thorough mechanistic analysis of the effects of bariatric surgery on multiple mechanisms important for the absorption, bioavailability and overall pharmacokinetics of lamotrigine.

Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin.

Bariatric surgery is an effective treatment for severe obesity and related comorbidities, such as type II diabetes. Gastric bypass surgery shortens the length of the intestine, possibly leading to altered drug absorption. Metformin, a first-line treatment for type II diabetes, has permeability-dependent drug absorption, which may be sensitive to intestinal anatomic changes during bypass surgery, including Roux-en-Y gastric bypass (RYGB).

Lamotrigine therapy in patients after bariatric surgery: Potentially hampered solubility and dissolution.

Bariatric surgery is an effective treatment of obesity and related comorbidities. With surgery, the stomach undergoes major anatomical/physiological changes that may affect the oral exposure of drugs, especially marginally soluble weak bases, such as lamotrigine. The aim of this work was to study the solubility/dissolution of lamotrigine in conditions simulating the stomach before vs.

Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review, meta-analysis, network meta-analysis, and meta-regression.

Background: Many health benefits of bariatric surgery are known and well-studied, but there is scarce data on the benefits of bariatric surgery on the thyroid function.

Objective: We aimed to make a meta-analysis regarding the impact of bariatric surgery on thyroid-stimulating hormone (TSH) levels, levothyroxine dose, and the status of subclinical hypothyroidism.

Setting: Systematic review and meta-analysis.

Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation.

The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g.