Co-solvent and complexation systems

Abstract

Co-solvent and polyethylene glycol (PEG)-based solubilization techniques for the delivery of poorly soluble drugs are discussed in this chapter. The properties of excipients and the physicochemical principles are presented for formulating each type of the solubilized formulations. Co-solvents are commonly used in combination with surface-active solubilizers to increase the solubilizing capacity and to improve the in vivo emulsification of self-emulsifying formulations. In PEG-based delivery systems, drug is either dispersed as micronized crystalline particles (via the formation of eutectic mixtures) or present in its amorphous state. Improvement in absorption from a PEG matrix is due to (1) fast dissolution rate of drug from the dosage forms and (2) higher transient solubility of the drug substance in gastrointestinal tract. Various manufacturing techniques to process the solubilized formulations into oral dosage forms are also discussed in this chapter. For the formulations that are liquid under ambient conditions, encapsulation into soft gelatin or hard gelatin capsules is the most common manufacturing method. Semi-solid and solid-solubilized formulations that are liquid at a higher temperature (50–70 °C) can be encapsulated into hard gelatin capsules as molten liquids at elevated temperature. Semi-solid or solid matrices are formed inside the capsules when the molten materials are cooled to ambient temperature. Spray congealing and fluidized bed melt granulation are alternative manufacturing processes to convert the solubilized formulations with high melting/softening points into granules that can be readily processed into capsules or tablets. Powdered solution technology can also be applied to transform the solubilized formulation of low-dose drug into free flowing powder by absorbing the formulation into solid carriers. In addition, the interest in using cyclodextrins (CDs) for drug solubilization has proven beneficial for delivery of poorly water-soluble drugs through the formation of inclusion complexes. This chapter provides an update with studies of drug-CD inclusion complexes, characterization of the complexes and examples of commercial products containing CDs. The current authors would like to thank and acknowledge the significant contributions of the previous authors of this chapter from the first edition. This current second edition chapter is a revision and update of the original authors’ work.