Pharmaceutically acceptable vehicles

Identification of pharmaceutically acceptable vehicles that afford sufficient solubilization while maximizing physiological compatibility for preclinical pharmacokinetic evaluation is critical. The most frequently used solubilization techniques include pH manipulation for ionizable compounds use of cosolvents such as PEG 400, ethanol, DMSO, and propylene glycol micellar solubilization with surfactants such as Tween 80 or SLS complexation with cylodextrins [40]. By using the solubilization techniques, the enhancement in solubility of poor water-soluble compounds can be significant compared to aqueous solubility and can facilitate the absorption of drug molecules in the gastrointestinal tract when delivered in solution form. 

Medicinal chemists should be aware that inexperienced biologists can erroneously conclude that poorly aqueous soluble compounds are orally absorbed when compounds are dosed in pharmaceutically unacceptable solvents. Always ask what is the dosing vehicle Heroic combinations of DMSO, Cremophor, poly(ethylene glycol), Tween-80 and ethanol are unacceptable and misleading. In case of doubt consult with a pharmaceutical scientist colleague. The reliable standards are an aqueous solution (with perhaps a trace of DMSO) or a suspension (perhaps stabilized with an acceptable quantity of adjuvant, e.g. Tween-80). 

Nationally, the annual number of deaths from opioid overdoses now exceeds the number of deaths caused by motor vehicle accidents [reference CDC website]. Regardless of whether we view these issues from the perspective of patients, physicians, or regulators, the status quo is clearly not acceptable. As the public health agency responsible for oversight of pharmaceutical safety and effectiveness, we recognize that this crisis demands solutions. We are committed to action, and we urge others to join us. 

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