Understanding the degradation pathway of a poorly water-soluble drug formulated in PEG-400

Soft Gelatin Capsules (Softgels)

“…100,[256][257][258][259][260] Though these reaction products may be ultimately hydrolyzed back to their parent compounds in the GIT, the bioavailabilities of the parent compounds could be reduced significantly. 100,[256][257][258][259][260] Though these reaction products may be ultimately hydrolyzed back to their parent compounds in the GIT, the bioavailabilities of the parent compounds could be reduced significantly.…”

“…During the softgel formulation development for a poorly water soluble investigational compound, VX-497, solubilized in PEG 400, Kochling et al 260 demonstrated the hydrolysis of urea bonds in the compound even at storage temperatures as low as 58C. During the softgel formulation development for a poorly water soluble investigational compound, VX-497, solubilized in PEG 400, Kochling et al 260 demonstrated the hydrolysis of urea bonds in the compound even at storage temperatures as low as 58C.…”

Influence of excipients on solubility and dissolution of pharmaceuticals

“…Within the formulation process, excipients are commonly used. Different polymers, e.g., polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), were reported to be suitable formulation materials for many poorly soluble APIs (Caron et al, 2010;Joshi et al, 2004;Kochling et al, 2007;Lakshman et al, 2008;Papadimitriou et al, 2012;Windbergs et al, 2009). Moreover, sugars, e.g., mannitol, are often used for pharmaceutical formulations (Liao et al, 2005;Littringer et al, 2013).…”

Kinetics of the Esterification of Active Pharmaceutical Ingredients Containing Carboxylic Acid Functionality in Polyethylene Glycol: Formulation Implications

“…Instead, there are scattered examples in the literature, where the use of PEG as an excipient shows a negative impact on the stability of the API concerning the formation of reaction products between API and reactive peroxides found in PEG . In addition, a few investigations have been published concerning an esterification reaction involving PEG and APIs containing carboxylic acid functionality . If PEG esters are formed in a formulation, they could theoretically be converted back into the parent compound because of hydrolytic and/or enzymatic cleavage in the human body.…”