The solubility of 17 β-oestradiol in aqueous polyethylene glycol 400

Abstract

The solubility of 17 beta-oestradiol (E2) in aqueous solutions of polyethylene glycol (PEG) 400 has been measured at 35 degrees C. Up to 80% w/w PEG the solubility data conform to a log linear equation ln S = ln Sw + f sigma where S is the E2 concentration in the water/cosolvent mixture, Sw is E2 solubility in water, f is the weight fraction of PEG 400 and sigma is a parameter representing the solubilizing power of the cosolvent for the drug. Above 80% PEG the relationship becomes less convincing, with significant deviation from anticipated values. Reasons for these aberrations are discussed. It is suggested that conformational changes may be induced in the PEG by the addition of small quantities of water. Deviations noted for the melting point, viscosity and density data of PEG 400-water solutions may also confirm this suggestion.

Paclitaxel distribution in poly(ethylene glycol)/poly(lactide-co-glycolic acid) blends and its release visualized by coherent anti-Stokes Raman scattering microscopy

“…The aqueous solubility of a poorly-water soluble drug was shown to be significantly enhanced by up to five orders of magnitude at 80 wt.% of PEG (MW 400) [27,28]. The PTX solubility in PEG dendrimers was even higher than that in PEG (MW 400) solution at the same weight concentration [29,30], probably due to the high local density and conformation arrangement inside the PEG dendrimer.…”

“…The PTX solubility in PEG dendrimers was even higher than that in PEG (MW 400) solution at the same weight concentration [29,30], probably due to the high local density and conformation arrangement inside the PEG dendrimer. It has been hypothesized that the conformation of PEG chains is rearranged from helix to Zig-Zag which contributes to the high solubility of the drug in an aqueous solution [27]. It has also been speculated that crystalline hydrophobic drug may form hydrogen bonding with PEG in solid solution [31].…”

Soft Gelatin Capsules (Softgels)

“…40,41 The use of volatile components, such as ethyl alcohol, in the fill formulations is limited due to their ability to rapidly diffuse through the shell material, and carrying out other fill components in the process. [68][69][70][71][72] The solvent capacity of a hydrophilic solvent, such as polyethylene glycol and propylene glycol, for a hydrophobic compound has been shown to fall approximately logarithmically as the formulation is diluted with water. [61][62][63][64][65][66][67] However, while polyethylene glycols often may have high solubilizing power for some poorly water soluble compounds, the high affinity of these vehicles for water can potentially lead to the precipitation of dissolved compounds when the formulation comes into contact with an aqueous environment in vitro or in vivo.…”

“…The rate and extent of water migration is influenced by the composition of shell formulation (e.g., type and concentration of plasticizer, presence of additives), 37,43 composition of fill formulation, 40,41,69,72,139 and environmental conditions to which the softgels are subjected to. The objective of improving bioavailability of a compound through solubilization may be defeated if the solubilized compound crystallizes either within the softgel due to water migration 68,69 or upon coming into contact with the aqueous fluids in the GIT. The objective of improving bioavailability of a compound through solubilization may be defeated if the solubilized compound crystallizes either within the softgel due to water migration 68,69 or upon coming into contact with the aqueous fluids in the GIT.…”

Development of ALZET® osmotic pump compatible solvent compositions to solubilize poorly soluble compounds for preclinical studies

“…19 Similar findings have also been reported for other poorly water soluble compounds solubilized in hydrophilic, non-aqueous vehicles. 17,[21][22][23] Crystallization of a compound can have the potential to cause pain at implanted site, erratic blood levels, and uneven or delayed pharmacokinetic profiles. 15,18 The expected crystallization of the compound in the aqueous environment at the animal tissue where the pump is implanted precluded the use of neat PEG 300 as a vehicle for ELND006.…”