Mutagenic and genotoxic QSAR prediction of dimer impurity of gliflozins; canagliflozin, dapaglifozin, and emphagliflozin and evaluation by Ames and micronucleus test.

Canagliflozin, Dapagliflozin, and Empagliflozin, glucagon-like peptide-1 receptor agonists, are indicated for managing type II diabetes. Although the genotoxicity profiles of these drugs are well-explored, limited information exists regarding the genotoxic potential of their impurities. In this investigation, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin underwent both and assessments for mutagenic potential.

HME-assisted formulation of taste-masked dispersible tablets of cefpodoxime proxetil and roxithromycin.

Objectives: Antibiotics are the most commonly administered medications among pediatric patients. However most of the time, accurate dose administration to children becomes a problem due to the extremely bitter taste. Cefpodoxime proxetil (CP) and roxithromycin (ROX) are antibiotics often prescribed to the pediatric population and have a bitter taste.

Microbial Profile, Antimicrobial Susceptibility, and Prevalence of MDR/XDR Pathogens Causing Medical Device Associated Infections: A Single Center Study.

Background: There is a scarcity of studies evaluating the microbial profile, antimicrobial susceptibility, and prevalence of MDR/XDR pathogens causing medical device-associated infections (MDAIs). The present study was sought in this regard.

Materials And Methods: An ambispective-observational, site-specific, surveillance-based study was performed for a period of 2 years in the intensive care unit (ICU) and high dependency unit (HDU) (medicine/surgery) of a Tertiary-care University Hospital.

An Overview of Chemistry, Kinetics, Toxicity and Therapeutic Potential of Boldine in Neurological Disorders.

Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties.

Design, development, and in-vitro/in-vivo evaluation of docetaxel-loaded PEGylated solid lipid nanoparticles in prostate cancer therapy.

Docetaxel (DOC) is a potent anticancer molecule widely used to treat various cancers. However, its therapeutic efficacy as a potential anticancer agent has been limited owing to poor aqueous solubility, short circulation time, rapid reticuloendothelial system uptake, and high renal clearance, which consecutively showed poor bioavailability. In the present investigation, we developed polyethylene glycol (PEG) decorated solid lipid nanoparticles (SLN) using the solvent diffusion method to increase the biopharmaceutical properties of DOC.

Brain Targeted Curcumin Loaded Turmeric Oil Microemulsion Protects Against Trimethyltin Induced Neurodegeneration in Adult Zebrafish: A Pharmacokinetic and Pharmacodynamic Insight.

Purpose: Aromatic turmerone, a major constituent of turmeric oil, has been recently reported for proliferation of neural stem cell showing great potential for effective treatment in neurodegenerative disorders. However, its effect as oral brain targeted formulation for neuroprotection has not yet reported. The objective of the study was to investigate the pharmacokinetic of curcumin loaded turmeric oil microemulsion for brain targeting and probing the protective effect against trimethyltin induced neurodegeneration in adult zebrafish.

Preparation and Optimization of Liposome Containing Thermosensitive Nasal Hydrogel System for Brain Delivery of Sumatriptan Succinate.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS).

3D printing of pharmaceuticals: approach from bench scale to commercial development.

Background: The three-dimensional (3D) printing is paradigm shift in the healthcare sector. 3D printing is platform technologies in which complex products are developed with less number of additives. The easy development process gives edge over the conventional methods.

Formulation and Characterization of Nanostructured Lipid Carriers of Rizatriptan Benzoate-Loaded Nasal Gel for Brain Targeting.

Intranasal route provides large surface area, avoids first-pass metabolism, and results in improved drug absorption. Intranasal delivery targets the drug to the brain for treatment of central nervous diseases viz migraine. The objective of the study was to formulate in situ nasal gel containing rizatriptan benzoate (RB)-loaded nanostructured lipid carriers (NLCs).

Delocalized Lipophilic Cation Triphenyl Phosphonium: Promising Molecule for Mitochondria Targeting.

The mitochondria are a dynamic powerhouse organelle that contributes greatly to cancer therapy. Solving the current problems that occur mostly in chemotherapy and diagnosis of various cancers targeting the Mitochondria is an implying approach. In this review, it is discussed how the tethering of mitochondrial-targeting moieties to chemotherapeutics, fluorescent dyes and photothermal molecules can enhance the anticancer effect.

Investigation of dimyristoyl phosphatidyl glycerol and cholesterol based nanocochleates as a potential oral delivery carrier for methotrexate.

Methotrexate (MTX), a biopharmaceutical classification system-IV anticancer drug, exhibits low therapeutic efficacy. Moreover, its clinical applications were restricted due to its multidrug resistance (MDR) in cancer and its toxic effects. The present investigation was to fabricate 1, 2-dimyristoyl--glycero-3-phospho--(1-glycerol) sodium (DMPG-Na), (3β)-cholest-5-en-3-ol (cholesterol) and calcium-based nanocochleates (NCs) as a potential oral delivery carrier for MTX to enhance its therapeutic efficacy with low toxicity.

An overview of regulations for bioequivalence assessment of locally acting orally inhaled drug products for the United States, Europe, Canada, and India.

Introduction: Bioequivalence is established by comparing the bioequivalence study results of generic drugs with the reference listed drug. Several global regulatory agencies have published the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches.

Areas Covered: The prime intent of the present article is to compare the regulatory guidance for bioequivalence assessment of locally acting OIDPs published by global regulatory authorities.

Investigation of 1,2-Dimyristoyl-sn-Glycero-3-Phosphoglycerol-Sodium (DMPG-Na) Lipid with Various Metal Cations in Nanocochleate Preformulation: Application for Andrographolide Oral Delivery in Cancer Therapy.

This study aimed at carrying out a preformulation investigation of nanocochleates (NCs) and develop andrographolide-loaded nanocochleates. Preformulation study comprised of exploring the effect of trivalent and divalent ions on transition temperature (TT) of lipid (DMPG-Na), on particle size (PS), entrapment efficacy (EE), zeta potential (ZP) of NCs, and effect of NCs on change in lipid solubility post-NC formation. Further, the andrographolide-loaded nanocochleates made with CaCl (ANDNCs) were characterized for ZP, PS, EE, X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), transition electron microscopy (TEM), in vitro release studies, in vitro anticancer potential on the cell line of human breast cancer (MCF-7), in vivo oral pharmacokinetic studies, and tissue distribution in female Wistar rats.

Preparation, optimization and preliminary pharmacokinetic study of curcumin encapsulated turmeric oil microemulsion in zebra fish.

The present investigation aimed to develop curcumin loaded turmeric oil microemulsion for brain targeting. An effort has been made to investigate the role of functional components in developing brain targeted formulation which could enhance the bioavailability and uptake of drug in the brain upon oral administration. Preliminary studies like solubility study, emulsification study and construction of the pseudo ternary phase diagram were performed for screening components.

Stimuli-responsive biodegradable polyurethane nano-constructs as a potential triggered drug delivery vehicle for cancer therapy.

Polyurethanes (PUs) constitute an essential class of stimuli-responsive and biodegradable material, which has significantly contributed to the advancement of polymers utilization in the biomedical field. The bio-erodible PUs construct an active corridor for facilitating drug into tumor cells, which has significantly impacted the progression of nano-micellar delivery systems. The self-assembledcolloidal PUs pose distinctive features such as enhancing the solubility of hydrophobic chemotherapeutics, rapid cellular uptake, triggered erosion and drug release, bio-stimulus sensitivity, improvement in the targeting and proficiency ofbioactive.

High-dose methotrexate-induced fulminant hepatic failure and pancytopenia in an acute lymphoblastic leukaemia paediatric patient.

Methotrexate treatment has been associated with an array of liver-related adverse events like asymptomatic transaminase elevations, fatal necrosis and fibrosis. Here we present a child with relapse Pre B cell acute lymphoblastic leukaemia who developed and died of fulminant hepatic failure and pancytopenia soon after the administration of high-dose MTX. This case is unusual due to a series of adverse events that led to severe toxicity.

Serum Methotrexate Level and Side Effects of High Dose Methotrexate Infusion in Pediatric Patients with Acute Lymphoblastic Leukaemia (ALL).

Methotrexate (MTX) is an extensively prescribed antimetabolite especially in the treatment of several pediatric cancers, though managing toxicities associated with methotrexate in high dose continues to be a challenge. A prospective study was carried out from April 2017 to October 2018. Children of either sex below 18 years at the time of enrolment and receiving high dose Methotrexate intravenous infusion over 24 h as a 2 g/m, 3 g/m and 5 g/m dose was included in the study.

Effect of USP Induction Ports, Glass Sampling Apparatus, and Inhaler Device Resistance on Aerodynamic Patterns of Fluticasone Propionate-Loaded Engineered Mannitol Microparticles.

The present investigation is to study the effect of two different induction ports (IP), i.e., USP IP and USP-modified IP equipped with andersen cascade impactor on in vitro aerodynamic performance along with the impact of USP-modified glass sampling apparatus on delivered dose uniformity of fluticasone propionate (FP) dry powder inhaler (DPI).

Development of High-Strength Extended-Release Multiparticulate System by Crystallo-co-agglomeration Technique with Integration of Central Composite Design.

The number of unit operations to be followed in the preparation of tablets was cumbersome and may introduce material as well as process-related critical parameters which may negatively affect the quality of final formulation. The hypothesis of the present research was to develop directly compressible, high-strength extended-release spherical agglomerates of talc containing indapamide by crystallo-co-agglomeration technique. Hydroxypropyl methylcellulose 15 cps and polyethylene glycol 6000 were used to impart the desired sphericity, strength, and deformability to agglomerates, respectively.

Case report on hypersensitivity to methotrexate infusion in a pediatric acute lymphoblastic leukaemia patient.

Methotrexate is extensively used in the treatment of various malignancies and autoimmune conditions. Methotrexate is associated with several toxicities, while hypersensitivity reactions to methotrexate are unusual, but have been reported in adult cancer patients. Hereby, we detail the case of a child with acute lymphoblastic leukaemia who developed a hypersensitivity reaction to high-dose methotrexate infusion (HDMTX) during the fourth cycle of HDMTX.

Phytoconstituent based dry powder inhalers as biomedicine for the management of pulmonary diseases.

Pulmonary disease represents a major global health issue. They are commonly treated by various synthetic molecules. But, frequent high-dose of oral and injectable drugs may lead to severe side effects and this juncture demands inhaled formulations that facilitate effective drug delivery to the lower airways with negligible side effects.

Potential of dry powder inhalers for tuberculosis therapy: facts, fidelity and future.

Tuberculosis (TB) is a contagious and airborne infectious disease caused by the pathogen Mycobacterium tuberculosis (Mtb). In spite of substantial research efforts, continuous multiple high-dose drug therapy regularly for 4-7 months can impede patient quality of life. The pathology of TB and biology of pulmonary airways permits for a variety of drug delivery strategies and natural route of infection denotes a more logical remedial approach for treatment of TB.

Emerging novel drug delivery strategies for bioactive flavonol fisetin in biomedicine.

Fisetin (FIS), a bioactive flavonol found in the smoke tree (Cotinus coggygria), vegetables, fruits and nuts. It exhibits various therapeutic activities such as anti-oxidant, anti-inflammatory, anti-invasive, anti-tumorigenic, anti-angiogenic, anti-diabetic, cardioprotective and neuroprotective activities. In spite of the ever rising support for therapeutic activities, its clinical application is mainly limited because of poor water solubility, high lipophilicity and low oral bioavailability.

Development of novel biotinylated chitosan-decorated docetaxel-loaded nanocochleates for breast cancer targeting.

The motive of study was to develop biotinylated chitosan (BI-CHI) decorated docetaxel (DTX) loaded nanocochleates (BI-CHI-DTX-NC) to achieve controlled drug release, improve bioavailability, targeted delivery and enhanced anticancer potency with the reduced systemic toxicity of DTX. The development involved the loading of DTX to nanocochleates (DTX-NC) through conversion of dimyristoylphosphatidylglycerol-sodium (DMPG-Na) and cholesterol bearing liposome on addition of calcium ions, followed by encapsulated DTX-NC with BI-CHI (BI-CHI-DTX- NC) and compared with DTX and DTX-NC. The release of DTX indicated strong pH dependence and implies strong hydrogen-bonding between nanocochleates and DTX.

Development of novel biofunctionalized chitosan decorated nanocochleates as a cancer targeted drug delivery platform.

A new family of biofunctionalized chitosan decorated nanocochleates-mediated drug delivery system was developed that involves uniquely combining nanocochleates with anticancer drug for controlled drug release, targeted delivery, improved bioavailability with reduced toxicity. This system was developed by loading of doxorubicin (DOX) to nanocochleates (DOX-NC) through conversion of negatively charged dimyristoylphosphatidylcholine (DMPC) phospholipid and cholesterol-bearing vesicles on addition of calcium ions, followed by encapsulation DOX-NC with folic acid conjugated chitosan (FA-CHI-DOX-NC). The release of DOX indicated strong pH dependence and implies hydrogen-bonding interaction between nanocochleates and DOX.