Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach.

The current research work focuses on understanding the reported discrepancies and our observations in the dissolution profiles of warfarin sodium tablets and potential patient-based failure modes during oral warfarin therapy. It was hypothesized that freely soluble crystalline warfarin sodium (WAR) at first transforms into noncrystalline warfarin sodium (WAR) under stress conditions. The WAR → WAR conversion facilitates the rapid formation of the poorly soluble unionized form, which could lead to dissolution failures and potential poor in vivo performance.

Insulin Dosage Adjustments After Initiation of GLP-1 Receptor Agonists in Patients With Type 2 Diabetes.

Background: Combination of insulin and GLP-1RAs have shown reductions in the HbA1c, body weight, and the risk of hypoglycemia. To date, there are conflicting data regarding the effect of GLP-1RAs on insulin dosage(s).

Objective: The objective of this study was to evaluate adjustments of insulin doses upon initiation of GLP-1RAs.

Physiologically based pharmacokinetic modeling of altered tizanidine systemic exposure by CYP1A2 modulation: Impact of drug-drug interactions and cigarette consumption.

Tizanidine is an alpha2-adrenergic agonist, used to treat spasticity associated with multiple sclerosis and spinal injury. Tizanidine is primarily metabolized by CYP1A2 and is considered a sensitive index substrate for this enzyme. The physiologically based pharmacokinetic (PBPK) modeling platform Simcyp® was used to evaluate the impact of CYP1A2 modulation on tizanidine exposure through drug-drug interactions (DDIs) and host-dependent habits (cigarette smoking).

Evaluation of local bioavailability of metronidazole from topical formulations using dermal microdialysis: Preliminary study in a Yucatan mini-pig model.

Dermal microdialysis (dMD) can measure the rate and extent to which a topically administered active pharmaceutical ingredient (API) becomes available in the dermis. Using multiple test-sites on the same subject, and replicate probes at each test-site, it is feasible to compare the cutaneous pharmacokinetics of an API from different topical dermatological drug products in parallel on the same subject with this technique. This study design would help to reduce variability.

Pediatric Nephrotic Syndrome: Pharmacologic and Nutrition Management.

Nephrotic syndrome is a common kidney disease during childhood that is characterized by alterations in glomerular filtration and leads to protein, fluid, and nutrient loss in the urine. Most patients experience peripheral, gravity-dependent edema; however, serious cases exhibit anasarca and ascites. Many long-term complications of the disease exist due to the underlying pathology and the therapies used for treatment, including metabolic bone disease, micronutrient deficiencies, and hyperlipidemia.

Angiotensin receptor neprilysin inhibitor use in patients with left ventricular assist devices: A single-center experience.

Though left ventricular assist devices (LVADs) are an increasingly common therapy for ACC/AHA Stage D heart failure, the optimal medical therapy for patients with LVADs is not known. We sought to evaluate the safety and efficacy of angiotensin receptor neprilysin inhibitor (ARNi) therapy in our single center LVAD patient experience. We evaluated patients implanted with LVADs at Columbia University Irving Medical Center between August 2010 and May 2019, and who were treated with an ARNi for at least 3 months.

Loop Diuretics: Clinical Application Information for Nephrology Nurses and Practitioners.

Loop diuretic medications work by inhibiting sodium reabsorption in the renal tubules. The net effect is increasing in urinary sodium and water excretion. Loop diuretics are routinely used for many clinical indications, and nephrology practitioners are well informed in the management of their use in daily practice.

Protocol development, validation, and troubleshooting of in-situ fiber optic bathless dissolution system (FODS) for a pharmaceutical drug testing.

Currently, there is no systematic approach available for the validation, quantitative assessment, and troubleshooting for the in-situ fiber optic/bathless dissolution system (FODS). In this report, a dissolution protocol was developed and validated for a model product, chlorpheniramine maleate (CPM) 4 mg IR tablets. Dissolution runs were conducted at 37 ± 0.

A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators.

What Is Known And Objective: Treatment with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has led to improved clinical outcomes and an increase in lifespans of cystic fibrosis (CF) patients. As CF patients continue to live longer, they are at risk for developing adverse drug reactions associated with polypharmacy and CFTR modulators.

Comment: The authors aim to describe safety concerns of the current combination CFTR modulators, based upon a literature review, including notable safety concerns and recommendations for drug-drug interactions.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

Aim: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes.

Methods: A 3 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA).

Discovery and SAR of Novel Disubstituted Quinazolines as Dual PI3Kalpha/mTOR Inhibitors Targeting Breast Cancer.

The dual PI3Kα/ m TOR inhibitors represent a promising molecularly targeted therapy for cancer. Here, we documented the discovery of new 2,4-disubstituted quinazoline analogs as potent dual PI3Kα/sm TOR inhibitors. Our structure based chemistry endeavor yielded six excellent compounds , and with single/double digit nanomolar IC values against both enzymes and acceptable aqueous solubility and stability to oxidative metabolism.

(2,3)-Dihydroxybutanoic Acid Synthesis as a Novel Metabolic Function of Mutant Isocitrate Dehydrogenase 1 and 2 in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) frequently harbors mutations in isocitrate 1 () and 2 () genes, leading to the formation of the oncometabolite (2)-hydroxyglutaric acid (2R-HG) with epigenetic consequences for AML proliferation and differentiation. To investigate if broad metabolic aberrations may result from and mutations in AML, plasma metabolomics was conducted by gas chromatography-mass spectrometry (GC-MS) on 51 AML patients, 29 / wild-type (WT), 9 with IDH1R132, 12 with IDH2R140 and one with IDH2R172 mutations. Distinct metabolic differences were observed between IDH1/2 WT, and patients that comprised 22 plasma metabolites that were mainly amino acids.

Anemia in Children With Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with nonspecific symptoms, such as irritability, headaches, fatigue, dizziness, and anorexia. In IBD patients, the etiology of anemia is often multifactorial.

Clinical and economic impact of the use of dexmedetomidine for sedation in the intensive care unit compared to propofol.

Background Despite the advantages of dexmedetomidine (DEX) over propofol (PRO) including minimal respiratory depression and the potential for preventing and/or treating intensive care unit (ICU) delirium, PRO has been the preferred agent due to its lower cost. However, the acquisition cost of DEX has considerably decreased as a generic version of DEX has recently become available. Objective To evaluate clinical and economic outcomes of DEX-based sedation compared to PRO in the ICU.

Current Perspectives of Anticoagulation in Patients With COVID-19.

Thromboembolism and myocardial injury is common in patients with COVID-19. Low-molecular-weight heparin appears to be associated with a good prognosis in patients with COVID-19 and has the ability to reduce coagulation and inflammation markers. Hospitalized patients with COVID-19 should be placed on thromboprophylaxis with the option of full therapeutic anticoagulation or tissue plasminogen activator in high-risk or mechanically ventilated patients.

A heart failure themed escape room approach to enhance pharmacy student learning.

Introduction: The purpose of this study was to design, pilot, and evaluate the efficacy of an educational escape room to enhance second professional year doctor of pharmacy students' knowledge of heart failure medicinal chemistry, pharmacology, and therapeutics in an integrated Modular Organ Systems Therapeutics (MOST) course and to assess students' perceptions of the game.

Methods: Heart failure pharmacology, medicinal chemistry, and pharmacotherapeutics were taught in MOST prior to the escape room activity. Students were randomized into groups of approximately eight.

Use of a virtual patient simulation program to enhance the physical assessment and medical history taking skills of doctor of pharmacy students.

Introduction: To evaluate if utilizing a virtual simulated patient program in a required pharmacy course improves the health history taking and physical assessment skills of first-year professional pharmacy students.

Methods: During a 14-week course students registered for a web-based virtual patient simulation program. Students were assigned a virtual patient case to complete during weeks one and 13 of the course.

Development and Validation of Sample Preparation and an HPLC Analytical Method for Dissolution Testing in Fed-State Simulated Gastric Fluid-Illustrating Its Application for Ibuprofen and Ketoconazole Immediate Release Tablets.

Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components.

Structure-mechanics and improved tableting performance of the drug-drug cocrystal metformin:salicylic acid.

Drug-drug cocrystals (DDC) represent a unique subset of pharmaceutical materials offering distinct advantages in combination therapies, pharmacokinetics, and patient compliance. However, their structure-function relationships are rarely reported despite its central importance in successful medicine. A material-sparing approach consisting of a molecular and structural perspective is reported to evaluate tabletability of a model DDC, metformin:salicylic acid, relative to its components: metformin HCl (MET) and sodium salicylate (SAL).

In and Beyond COVID-19: US Academic Pharmaceutical Science and Engineering Community Must Engage to Meet Critical National Needs.

The supply of affordable, high-quality pharmaceuticals to US patients has been on a critical path for decades. In and beyond the COVID-19 pandemic, this critical path has become tortuous. To regain reliability, reshoring of the pharmaceutical supply chain to the USA is now a vital national security need.

A Call to Action: The Role of Antiretroviral Stewardship in Inpatient Practice, a Joint Policy Paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine.

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists.

Pharmacokinetics of linezolid for methicillin-resistant Staphylococcus aureus pneumonia in an adult receiving extracorporeal membrane oxygenation.

Purpose: We present a case of a 55-year-old man post right lung transplantation receiving ECMO for treatment of respiratory failure secondary to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.

Summary: Extracorporeal membrane oxygenation (ECMO) is a frequently utilized support therapy for patients with cardiac and/or respiratory failure. Dosing of medications during ECMO can be challenging due to several factors, including sequestration of medications within ECMO circuits, alterations in volume of distribution, and changes in drug clearance.

Contribution of Crystal Lattice Energy on the Dissolution Behavior of Eutectic Solid Dispersions.

In the literature, it is reported that eutectics lead to the enhanced dissolution of a poorly soluble compound. However, the solubility theory suggests that since crystal structures of two components are unchanged that all else being equal, the dissolution rates of a fused mixture (FM) should be the same as a physical mixture (PM). The influence of crystal lattice energy on dissolution profiles was investigated using the PM and FM.

Stress-Based Production, and Characterization of Glutathione Peroxidase and Glutathione S-Transferase Enzymes From .

More attention has been recently directed toward glutathione peroxidase and s-transferase enzymes because of the great importance they hold with respect to their applications in the pharmaceutical field. This work was conducted to optimize the production and characterize glutathione peroxidase and glutathione s-transferase produced by KU720558 using Plackett-Burman and Box-Behnken statistical designs. To assess the impact of the culture conditions on the microbial production of the enzymes, colorimetric methods were used.