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Browse the failure-mode index

12 real negative results, null findings, and replication failures in Pharmacology, Toxicology and Pharmaceutics. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Replication FailurePharmacology, Toxicology and Pharmaceutics

Solvent‐Free Ball‐Milling Biginelli Reaction by Subcomponent Synthesis

Prasit Kumar Sahoo, Anima Bose, Prasenjit Mal · 2015 · European Journal of Organic Chemistry

Abstract We report here an understanding of systems chemistry on small molecules through covalent mechanochemistry. As a proof‐of‐concept, the multicomponent Biginelli reaction by subcomponent synthesis was considered as a model system.…

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter‐observational study

T. Acciavatti, Matteo Lupi, Rita Santacroce et al. · 2017 · Human Psychopharmacology Clinical and Experimental

OBJECTIVE: Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this…

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

Acute liver failure

Laura Blackmore, William Bernal · 2015 · Clinical Medicine

Acute liver failure (ALF) is a rare critical illness with high mortality whose successful management requires early recognition and effective initial management. Though it may result from a wide variety of causes, in the UK and much of the…

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Negative / Null Result ReportPharmacology, Toxicology and Pharmaceutics

A Lack of Significant Effect of POR*28 Allelic Variant on Tacrolimus Exposure in Kidney Transplant Recipients

Anne‐Sophie Jannot, Xavier Vuillemin, Isabelle Étienne et al. · 2016 · Therapeutic Drug Monitoring

BACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxidoreductase (POR), which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of…

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

Development of a digital twin of a tablet that mimics a real solid dosage form: Differences in the dissolution profile in conventional mini-USP II and a biorelevant colon model

Michael Schütt, Konstantinos Stamatopoulos, Hannah Batchelor et al. · 2022 · European Journal of Pharmaceutical Sciences

The performance of colon-targeted solid dosage forms is commonly assessed using standardised pharmacopeial dissolution apparatuses like the USP II or the miniaturised replica, the mini-USP II. However, these fail to replicate the hydrodynamics and shear stresses in the colonic environment, which is crucial for the tablet's drug release process. In this work, computer simulations are used to create a digital twin of a dissolution apparatus and to develop a method to create a digital twin of a tablet that behaves realistically. These models are used to investigate the drug release profiles and s

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

Innovative dual-functional hybrid cationic PEGylated proniosomes as a smart nano-platform for Boosted vaginal delivery: multi-level in-vitro, ex-vivo, microbiological, and in-vivo studies

Sadek Ahmed, Osama Saher, Heba Attia et al. · 2026 · Frontiers in Pharmacology

Introduction: Vaginal candidiasis remains a recurrent fungal infection affecting millions of women worldwide, necessitating innovative local delivery systems to overcome poor drug solubility and mucosal barriers. This study introduces Dual-Functional Hybrid Cationic PEGylated Proniosomes (DHCPP) as a smart nano-platform designed to boost the vaginal delivery of Fenticonazole Nitrate (FTN). Methods: DHCPP systems were fabricated via the coacervation phase separation method and optimized using a full 2 3 factorial design, achieving a high desirability value of 0.931. The optimized DHCPP exhibite

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

Engineered Novel Brijaluronic Terpesomes for Brain-Targeted Quercetin Delivery: Optimization, Ex Vivo and Radiokinetics

Sadek Ahmed, Khaled M. Attallah, Marwa Eid Sayyed · 2026 · AAPS PharmSciTech

Abstract This research focuses on creating a novel Brijaluronic-based terpesomal system capable of transporting quercetin (QER) efficiently to the brain. The vesicles were fabricated through an ethanol-injection method and then refined using a structured optimization approach in Design-Expert® software. The influence of three main formulation parameters: terpene-to-drug ratio, surfactant type, and hyaluronic acid amount were evaluated. The optimization process was designed to maximize EE%, minimize VS, and maintain ZP within an acceptable stability range. The optimal formula hit a desirability

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

Harnessing Novel Tetra-Synergistic Bilosomes for Effective Otomycosis Management: Integrated In-Vitro, Microbiological and In-vivo Studies

Abdurrahman M. Fahmy, Osama Saher, Heba Attia et al. · 2026 · AAPS PharmSciTech

Abstract This study introduces and statistically optimizes novel Tetra-Synergistic Bilosomes (TSB), an advanced nano-platform for topical delivery of voriconazole (VOR) in otomycosis therapy. The term “Tetra-Synergistic” reflects the incorporation of four complementary components: Cremophor® EL, sodium deoxycholate, Brij® 58, and Brij® S2, working in synergy to enhance therapeutic efficacy. TSB was fabricated using the thin-film hydration method and optimized through a 2 3 D-optimal design. Three formulation factors were investigated: Cremophor® EL: VOR ratio, sodium deoxycholate: cholesterol

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Napabucasin Combined with Sorafenib in Japanese Patients with Unresectable Hepatocellular Carcinoma

Takuji Okusaka, Manabu Morimoto, Yuichiro Eguchi et al. · 2023 · Drugs in R&D

BACKGROUND AND OBJECTIVE: For patients with advanced hepatocellular carcinoma (HCC), the standard of care for many years has been sorafenib. Preliminary data have suggested that the combination of the NAD(P)H:quinone oxidoreductase 1…

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

The self-assembly of glycyrrhizic acid into nanofibrils

Suelen Gauna Trindade, Fernando Bonin Okasaki, Ashley P. Williams et al. · 2025 · Journal of Colloid and Interface Science

The self-assembly of glycyrrhizic acid (GA) in aqueous solutions has significant implications for soft matter science and material design. Here, we describe the self-assembly of GA under well-defined conditions, focusing on measurements of the critical aggregation concentration (CAC) - when GA dimers start stacking into nanofibrils, and of the critical gel concentration (CGC) - when nanofibrils entangle into a viscoelastic network. We examine in detail the structure at low concentrations and its evolution into a viscoelastic hydrogel, addressing the kinetic pathway. We highlight the dependence

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Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics

The multiple mechanisms and modes of cell death after acetaminophen overdose

Hartmut Jaeschke, Anup Ramachandran · 2025 · Exploration of Digestive Diseases

Acetaminophen (APAP)-induced liver injury and acute liver failure is a significant clinical problem worldwide; in addition, APAP overdoses in animals or in cell culture are used as popular models to study drug-induced liver injury mechanisms and test therapeutic interventions. Early assumptions that APAP toxicity is caused by a single mechanism resulting in a defined mode of cell death in hepatocytes had to be questioned when over the years many different mechanisms and modes of cell death were reported. Although many of the contradictory results and conclusions reported over the years can be

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