Water Migration from Soft Gelatin Capsule Shell to Fill Material and its Effect on Drug Solubility

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

“…68 Solutions can also be filled into soft gelatin capsules for which the solution temperature should remain <40°C. 79 Several hard gelatin 80,81 and soft gelatin 82 capsule products prepared according to these techniques have been marketed in recent years.…”

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.…”

“…54,[58][59][60] individual variability in the absorption have been shown to provide exceptionally high bioavailability and reduced inter-subject variability in plasma concentrations when dosed as solutions or suspensions in polyethylene glycols. 69,71 Serajuddin et al, 69 for example, demonstrated a sharp reduction in the solubility of a test compound in PEG 400 from 250 mg/ g to about 1.5 mg/g with an increase in water content from 0% to 50% in the formulation (Fig. [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.…”

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.…”