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As direct-acting oral anticoagulants (DOACs) have short half-lives of around 12 h, even a short gap in DOAC therapy may diminish anticoagulation effects, increasing risks of adverse clinical outcomes. We aimed to evaluate clinical consequences of a gap in DOAC therapy with atrial fibrillation (AF) and to identify its potential predictors. In this retrospective cohort study, we included DOAC users aged over 65 years with AF from the 2018 Korean nationwide claims database. We defined a gap in DOAC therapy as no claim for a DOAC one or more days after the due date of a refill prescription. We used a time-varying-analysis method. The primary outcome was a composite of death and thrombotic events including ischemic stroke/transient ischemic attack or systemic embolism. Potential predictors of a gap included sociodemographic and clinical factors. Among 11,042 DOAC users, 4857 (44.0 %) patients had at least one gap. Standard national health insurance, non-metropolitan locations of medical institutions, history of liver disease, chronic obstructive pulmonary disease, cancer, or dementia, and use of diuretics or non-oral agents were associated with increased risks of a gap. In contrast, history of hypertension, ischemic heart disease, or dyslipidemia were associated with a decreased risk of a gap. A short gap in DOAC therapy was significantly associated with a higher risk of the primary outcome compared to no gap (hazard ratio 4.04, 95 % confidence interval 2.95–5.52). The predictors could be utilized to identify at-risk patients to provide additional support to prevent a gap. [Display omitted] • Approximately half of elderly DOAC users had at least one gap in DOAC therapy. • This gap was significantly associated with a higher risk of death or thrombosis. • The predictors could be utilized to provide additional support to prevent a gap. [ABSTRACT FROM AUTHOR]

[Display omitted] Industrial-scale pharmaceutical applications still face many challenges in overcoming the low absorption and bioavailability of poorly water-soluble drugs. Hot-melt extrusion has emerged as a promising approach with continuous processing on an industrial scale for the preparation of drug delivery systems. Many reviews have mentioned the potential applications, processes, principles and advantages and disadvantages of hot-melt extrusion in the pharmaceutical industry. However, a focus on the recent progress of hot-melt extrusion, which investigates the impacts of processes and formulations of solid dispersions of poorly water-soluble drugs, is missing. In this review, various factors, including polymers, drug properties, additives and surfactants, in solid dispersion SD formulations by hot-melt extrusion will be discussed. Moreover, the effects of the hot-melt extrusion process on the physicochemical properties of solid dispersions will be mentioned. The utilization of molecular interactions in hot-melt extrusion to improve drug stability will also be described. Overall, this summary of recent studies on solid dispersion by hot-melt extrusion will provide perspectives and effectiveness for the development of formulations containing poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

Abstract: The present study aimed to improve the bioavailability of biochanin A, a poorly soluble bioflavonoid, via the preparation of solid dispersion (SD) using Solutol® HS15 and HPMC 2910. Solubility of biochanin A was enhanced by 8–60 folds as the drug-carrier ratio was increased in SDs. Furthermore, compared to pure biochanin A or physical mixture (PM), SDs significantly improved the dissolution rate and the extent of drug release. Particularly, SDs (Drug:Solutol® HS15:HPMC 2910=1:5:5 or 1:10:10) achieved the rapid and complete drug release (approximately 100% within 1h) at pH 6.8. The XRD patterns indicated that SDs might enhance the solubility of biochanin A by changing the drug crystallinity to amorphous state in addition to the solubilizing effect of hydrophilic carriers. The improved dissolution of biochanin A via SD formulation appeared to be well correlated with the enhanced oral exposure of biochanin A in rats. After an oral administration of SD (Drug:Solutol® HS15:HPMC 2910=1:10:10), C max and AUC of biochanin A were increased by approximately 13 and 5 folds, respectively, implying that SDs could be effective to improve the bioavailability of biochanin A. In conclusion, solid dispersion with Solutol® HS15 and HPMC 2910 appeared to be promising to improve the dissolution and oral exposure of biochanin A. [Copyright &y& Elsevier]

Abstract: To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q10 (CoQ10), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ10 was formulated. The solubility of CoQ10 was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ10 was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and 10% (v/v) Capryol 90 of each excipient showed minimum mean droplet size (about 240nm) and optimal drug release profile in water. The pharmacokinetic study in rats for the optimized formulation was performed and compared to powder formulation. SEDDS have significantly increased the C max and area under the curve (AUC) of CoQ10 compared to powder (P <0.05). Thus, this self-micro emulsifying drug delivery system should be an effective oral dosage form for improving oral bioavailability of lipophilic drug, CoQ10. [Copyright &y& Elsevier]

[Display omitted] Fucoidan is well known to have various biological functions and is often investigated for pharmaceutical applications. Several studies have been conducted on clinical applications of fucoidan in recent years, especially regarding its oral drug delivery. Although fucoidan has shown promising results in various dosage forms, its potential applications as a dietary supplement have been demonstrated, and recent studies show that oral administration of fucoidan is preferred. However, the focus on the oral delivery of fucoidan in recent studies has caused its potency in therapy to be understudied. This review aims to provide results on the promising fucoidan activity by oral administration with in vivo studies. In addition to using it as an active ingredient, the utilization of fucoidan as an excipient in oral drug delivery systems will be discussed. An overview of fucoidan administration by oral delivery in recent promising studies will provide a direction for further investigations in clinical applications, particularly for fucoidan, which has a broad spectrum of bioactive properties. [ABSTRACT FROM AUTHOR]

[Display omitted] The freeze-drying process has been particularly attractive for preparing tablets for controlled drug release. Although traditional methods, such as granulation or direct compression methods, have been used in various studies to produce tablets with controlled release, freeze-drying processes have been utilized in certain circumstances due to their distinct advantages. However, overall, further development of these strategies, which started with early studies on orally disintegrating tablets, is still necessary. In this review, the incorporation of different formulations into freeze-dried tablets will be discussed. Moreover, the use of excipients, freeze-drying conditions, formulation reconstitution and tablet structure for optimizing the performance of freeze-dried tablets will be reported, including strategies with nanoformulations and natural materials. Generally, this discussion with potential approaches will benefit further development of freeze-dried tablets containing drugs in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]