Recent Advances in Lipid-Based Formulation Technology

Abstract

Lipid-based formulations encompass a wide variety of delivery modes and technologies, ranging from immediate release to sustained release formulations, from liquids to semi-solids, from crystalline suspensions to lipid solutions, from systems containing small-molecule active pharmaceutical ingredients (APIs) to those containing more complex peptide-based molecules, and finally from those intended for oral administrations through to topicals and parenterals. The flexibility of lipid formulation technologies provides the potential to modify pharmaceutical properties such as stability and ease of manufacture, and pharmacokinetic properties such as enhanced absorption and bioavailability, sustained exposure and targeted delivery. With the exception of liposomal technologies (that represent a class of delivery system in their own right and have not been considered here), much of the interest in lipid-based formulations has focused on their use to enhance the oral bioavailability of poorly water-soluble drugs. Drugs with low water solubility continue to present a formidable challenge to effective drug development (1) and commonly show poor, variable, and fooddependent absorption and bioavailability after oral administration. Whilst great strides have been made in lead optimization strategies to design-out the physicochemical properties that lead to low water solubility, in many cases, structural changes that increase solubility also result in unacceptable reductions in potency. Indeed, the majority of reports describing changes in the patterns of physicochemical properties for new drug discovery candidates suggest that trends towards low water solubility are increasing rather than decreasing (2,3). Formulation strategies that facilitate the ‘rescue’ of compounds with intrinsically low water solubility, and that provide for robust and reproducible exposure after oral administration, therefore remain an important weapon in the drug development armory. Several strategies that enable effective delivery of poorly water-soluble compounds are apparent (1) and, in general, may be stratified as technologies that modify solute–solute interactions in the solid state, that enhance solute–solvent interactions in solution, that promote dissolution via changes in surface area, or combinations of the three approaches. Formulation technologies to enhance solubility and dissolution rate include salt formulation,modification of crystal form (amorphous, cocrystals, polymorphs), particle size reduction/nanomilling, alteration of solution/solubilisation conditions (cosolvents, surfactants, cyclodextrins etc.), and approaches such as solid dispersions and lipidbased formulations that may, in practice, achieve a number of these goals. For example, many solid dispersion and lipid-based formulations contain drug in a non-crystalline (amorphous/molecularly dispersed) form, circumventing the challenge to solubility provided by the crystal lattice, and also provide for ongoing solubilisation or stabilization of supersaturation via the inclusion of surfactants, lipids and/or polymers. The current theme issue focuses on the potential utility of lipid-based formulations as a means of enhancing the oral bioavailability of poorly water-soluble drugs. In addition, several manuscripts provide insight into the broader application of lipid-based drug delivery technologies, for example, to facilitate parenteral or site-specific delivery of lipophilic compounds. This is not to suggest any inherent superiority of lipid-based formulation technologies over others, and the appropriate choice of an enabling technology is clearly drug specific. However, for poorly water-soluble lipophilic drugs, lipid-based formulations provide a tried and tested delivery solution to overcome poor and variable oral bioavailability and are increasingly being utilized as a vehicle to achieve modulated or targeted delivery. Nonetheless, whilst lipid-based formulations have been used to good effect in a range of oral and parenteral drug products (4), several challenges to their broader utility remain. These C. J. H. Porter (*) :H. D. Williams :N. L. Trevaskis Drug Delivery Disposition and Dynamics Monash Institute of Pharmaceutical Sciences Monash University (Parkville campus) Melbourne, Victoria, Australia e-mail: chris.porter@monash.edu