Glimepiride is a third-generation sulfonylurea used in the management of type 2 diabetes mellitus. Despite its efficacy, glimepiride's therapeutic application is limited by its poor water solubility and short biological half-life, necessitating frequent dosing to maintain effective plasma concentrations. To overcome these challenges, the development of a sustained release formulation through solid dispersion techniques presents a promising strategy.

Objective: This study aims to formulate and evaluate a sustained release solid dispersion of glimepiride to enhance its solubility, bioavailability, and therapeutic efficacy, while reducing dosing frequency.

Solid dispersions of glimepiride were prepared using various hydrophilic carriers, including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropyl methylcellulose (HPMC), via solvent evaporation and melting techniques. Different ratios of drug to carrier were tested to identify the optimal formulation. The prepared solid dispersions were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X- Ray Diffraction (XRD) to assess drug-polymer interactions, thermal properties, and crystallinity changes.

The optimal solid dispersion was incorporated into sustained release matrix tablets using direct compression. Various excipients such as hydroxypropyl methylcellulose (HPMC K15M), ethyl cellulose, and carbopol were utilized to achieve sustained release profiles. Tablet formulations were evaluated for physical properties including hardness, friability, and uniformity of weight.

Dissolution tests were conducted using USP Type II dissolution apparatus in phosphate buffer (pH 7.4) to simulate intestinal conditions. The release profiles were analyzed using mathematical models (zero-order, first-order, Higuchi, and Korsmeyer-Peppas) to determine the kinetics and mechanism of drug release.

The FTIR and DSC analyses confirmed the absence of significant drug-polymer interactions, indicating chemical stability. XRD patterns revealed a reduction in the crystallinity of glimepiride in the solid dispersions, suggesting enhanced solubility. Among the carriers tested, HPMC-based solid dispersions exhibited the highest solubility enhancement. The sustained release tablets showed satisfactory physical properties, with hardness and friability within acceptable limits.

The in vitro dissolution studies demonstrated a controlled and sustained release of glimepiride over 24 hours. The release kinetics followed the Higuchi model, indicating diffusion-controlled release. The optimized formulation achieved a significant improvement in the dissolution rate compared to pure glimepiride, with approximately 80% drug release at 24 hours, demonstrating its potential for sustained therapeutic effect.

Vitamin E, a fat-soluble antioxidant, is known for its beneficial effects on cellular protection against oxidative stress. However, its interaction with anticoagulant medications has raised concerns and interest within the medical community. This study aims to evaluate the impact of Vitamin E on anticoagulant efficacy, focusing on the potential alterations in the therapeutic outcomes and safety profiles of commonly used anticoagulants such as warfarin and direct oral anticoagulants (DOACs).

The anticoagulant response is a critical factor in managing conditions like atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Warfarin, a vitamin K antagonist, has been a cornerstone in anticoagulation therapy but requires careful monitoring due to its narrow therapeutic index and interaction with various dietary and pharmacological agents. The newer class of DOACs, including drugs like dabigatran, rivaroxaban, and apixaban, offers more predictable pharmacokinetics and less frequent monitoring but remains susceptible to interactions affecting their efficacy and safety.

This study investigates the hypothesis that high doses of Vitamin E may enhance the anticoagulant effects, potentially leading to an increased risk of bleeding complications. The interaction is hypothesized to occur through several mechanisms, including the inhibition of vitamin K-dependent clotting factors and potentiation of the anticoagulant drugs' effects.

To test this hypothesis, a cohort of patients on stable anticoagulation therapy with either warfarin or DOACs was selected. The study involved a controlled administration of Vitamin E supplements at varying doses. Patients were monitored for changes in key indicators such as International Normalized Ratio (INR) for those on warfarin and specific coagulation assays for those on DOACs. Additionally, bleeding events and other adverse effects were meticulously recorded.

Preliminary findings indicate a dose-dependent interaction between Vitamin E and warfarin, evidenced by significant alterations in INR levels. Patients receiving higher doses of Vitamin E exhibited prolonged INR, necessitating adjustments in warfarin dosage to maintain therapeutic ranges. This potentiation effect aligns with the proposed mechanism of Vitamin E interfering with vitamin K metabolism, thereby amplifying warfarin's anticoagulant action. Interestingly, the interaction with DOACs presented a more complex picture. While some patients showed increased sensitivity to DOACs, others did not exhibit significant changes, suggesting that the interaction might be influenced by individual patient factors such as genetic variations in drug metabolism and baseline antioxidant status.

The safety analysis revealed an increased incidence of minor bleeding events in the group receiving high doses of Vitamin E, particularly among warfarin users. Major bleeding events were rare but

notable, reinforcing the need for cautious administration of Vitamin E in patients on anticoagulation therapy. These findings underscore the importance of personalized medicine approaches in managing anticoagulant therapies, taking into account the potential for nutrient-drug interactions.

This study contributes to the growing body of evidence on the complex interplay between dietary supplements and pharmacotherapy. The results highlight the need for healthcare providers to carefully evaluate and monitor patients who may be using Vitamin E supplements concurrently with anticoagulant medications. Recommendations for clinical practice include routine assessment of supplement use in patients prescribed anticoagulants and considering potential dose adjustments to mitigate the risk of adverse bleeding events.