Why Drugs Fail – A Study on Side Effects in New Chemical Entities

Antidepressant-Induced Liver Injury: A Review for Clinicians

“…Dr ug-induced liver injury (DILI), the fourth leading cause of liver damage in Western countries, is a matter of concern in the context of increasing drug availability and prescription (1). DILI is the most frequent cause of market withdrawal of a drug and rejection of applications for a marketing license in the United States (2).…”

Pharmaceutical Salts: Solids to Liquids by Using Ionic Liquid Design

“…However, solid forms of APIs often suffer from polymorphic conversion, low solubility, and a variety of factors which affect bioavailability associated with the final solid form [17,18,27]. Many phase II trials of new APIs end in failure due to their efficacy, often related to bioavailability and thus solubility [16][17][18]. These factors motivate the screening for novel solid forms, including salts, polymorphs, pseudopolymorphs (or solvates), and co-crystals ( Figure 3).…”

“…Historically, the pharmaceutical industry depends mostly on crystalline APIs. However, many formulations fail during testing because of issues as, for example, delivery mechanisms such as dissolution, transport, and bioavailability or poor control over polymorphism which can dramatically change properties such as solubility [16,17,18]. In the context of APIs, the counter ions could be selected to synergistically enhance the desired effects or to neutralize unwanted side effects of the active entity.…”

ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

“…ADME and drug metabolism PK reasons for failure fell from 40% to 11% [ 4 ]. Now, lack of efficacy and human toxicity are the major reasons for failure [ 12 ].…”