Development of a Formulation and In Vitro Evaluation of a Pulmonary Drug Delivery System for a Novel Janus Kinase (JAK) Inhibitor, CPL409116.

The pursuit of targeted therapies for cytokine-dependent diseases has led to the discovery of Janus kinase (JAK) inhibitors, a promising class of drugs. Among them, CPL409116, a selective dual JAK and rho-associated protein kinase inhibitor (ROCK), has demonstrated potential for treating conditions such as pulmonary fibrosis exacerbated by the COVID-19 pandemic. This study investigated the feasibility of delivering CPL409116 via inhalation, with the aim of minimizing the systemic adverse effects associated with oral administration.

Early life interventions metformin and trodusquemine metabolically reprogram the developing mouse liver through transcriptomic alterations.

Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance.

First-in-human study of CPL207280, a novel G-protein-coupled receptor 40/free fatty acid receptor 1 agonist, in healthy volunteers after single and multiple administration.

Aim: To assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of CPL207280, a new G-protein-coupled receptor 40 agonist developed to treat type 2 diabetes (T2D).

Methods: The phase 1 study in healthy volunteers (White, age 18-55 years, body mass index 18.5-29.

Hydration Patterns in Sodium Alginate Polymeric Matrix Tablets-The Result of Drug Substance Incorporation.

The purpose was to show, using destructive/nondestructive methods, that the interplay between water, tablet structure, and composition determine the unique spatiotemporal hydration pattern of polymer-based matrices. The tablets containing a 1:1 / mixture of sodium alginate with salicylic acid (ALG/SA) or sodium salicylate (ALG/SNA) were studied using Karl Fischer titration, differential scanning calorimetry, X-ray microtomography, and magnetic resonance imaging. As the principal results, matrix specific features were detected, e.

Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial.

Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a robust SR matrix tablet with a novel G-protein-coupled receptor 40 (GPR40) agonist for first-in-human studies and introduce a general workflow for the successful development of SR formulations for innovative APIs.

Spatiotemporal Analysis of Hydration Mechanism in Sodium Alginate Matrix Tablets.

Methods of spatiotemporal characterization of nonequilibrated polymer based matrices are still immature and imperfect. The purpose of the study was to develop the methodology for the spatiotemporal characterization of water transport and properties in alginate tablets under hydration. The regions of low water content were spatially and temporally sampled using Karl Fisher and Differential Scanning Callorimetry (spatial distribution of freezing/nonfreezing water) with spatial resolution of 1 mm.

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e.

Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc.