Fluid-filled hard gelatin capsules can be prepared from thixotropic gel formulations, the viscosity of which is lowered by adding suitable excipients or through the application of pressure during the filling process. While this technique has proven useful in certain instances, it has found only limited application due to the difficulty of identifying appropriate excipients from which these formulations can be prepared.
A thixotropic, lipid-based formulation of the poorly water-soluble drug, propantheline bromide, which was suitable for hard gelatin encapsulation at room temperature was prepared by first dissolving the drug in Miglyol 829. Subsequent incorporation of colloidal silicon dioxide increased the viscosity of the fill material in proportion to the amount added, while simultaneously increasing the in vitro dissolution rate of the drug (60). In another study, colloidal silicon dioxide was used as a gelling agent to formulate a SEDDS from a mixture of an oil (diesters of caprylic/capric acids; Captex 200), a surfactant (polysorbate 80) and a cosurfactant (C8/C10 mono-/diglycerides; Capmul MCM) (61).
Jirby et al. (62) described the preparation of semi-solid "amphiphilogel" formulations of poorly water-soluble drugs from combinations of solid and liquid surfactants or amphiphiles. The semi-solid surfactants, Span 40 (sorbitan monopalmi-tate) or Span 60 (sorbitan monostearate), were used as solid gelators and combined with the liquid surfactants, Span 20 (sorbitan monolaurate) or a Tween (polysor-bate 20 or polysorbate 80). The solid and liquid components were heated together to 60°C to enable homogeneous mixing and gels were formed when mixtures were cooled to room temperature. The authors reported that bioavailability of poorly water-soluble drugs could be enhanced by incorporating them in such gels.
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