Lipid-Based Formulations
The understanding in design, classification, and characterization of Lipid-Based Formulations (LBFs) has evolved greatly over the last two decades. LBFs include simple lipid solutions, self-emulsifying and self-microemulsifying drug delivery systems (SEDD
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Lipid-Based Formulations Justin LaFountaine, Ping Gao, and Robert O. Williams III
Abstract The understanding in design, classification, and characterization of Lipid-Based Formulations (LBFs) has evolved greatly over the last two decades. LBFs include simple lipid solutions, self-emulsifying and self-microemulsifying drug delivery systems (SEDDS and SMEDDS), and surfactant-cosolvent solutions, designated as Type I to IV systems depending on their composition and properties. Notably, this chapter details several mechanistic studies that have helped to elucidate the pathways involved for increased absorption of poorly soluble drugs, which have aided in the design and standardization of LBF in vitro characterization methods. Much of this work has evolved through the recent Lipid Formulations Classification System Consortium, an academic-industrial group of experts and stakeholders that have worked to advance the state of the art. The role of sustained supersaturation, triggered by LBF dilution and digestion, in enhancing drug absorption is discussed along with formulation variables intended for this purpose. Finally, a short review is provided on solidification of LBFs and the benefits and challenges associated with the techniques involved. Keywords Lipid-based formulations (LBFs) • Self-emulsifying drug delivery systems (SEDDS) • Self-microemulsifying drug delivery systems (SMEDDS) • Supersaturation • Digestion
7.1 Introduction Oral delivery of Lipid-Based Formulations (LBFs) has been utilized for decades as a means to improve absorption of poorly water-soluble, lipophilic drugs. For dissolution rate limited drugs, LBFs present the drug in a pre-solubilized form to the J. LaFountaine (*) • R.O. Williams III Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA e-mail: [email protected]; [email protected] P. Gao Abbvie Inc., North Chicago, IL USA e-mail: [email protected] © American Association of Pharmaceutical Scientists 2016 R.O. Williams III et al. (eds.), Formulating Poorly Water Soluble Drugs, AAPS Advances in the Pharmaceutical Sciences Series 22, DOI 10.1007/978-3-319-42609-9_7
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gastrointestinal tract for absorption. For solubility-limited drugs, several mechanisms have been proposed for enhanced absorption. These include increased drug permeability via transporters (Constantinides and Wasan 2007; Goole et al. 2010), through presentation after collisional transfer of bile-salt mixed micelles (Gao and Morozowich 2007), decreased first-pass metabolism (Patel and Brocks 2009; Trevaskis et al. 2006), and, for highly lipophilic drugs (e.g. log P > 6), an increase in lymphatic transport (O’Driscoll 2002; Trevaskis et al. 2008). Recently, however, understanding has evolved implicating dilution and/or digestion-induced supersaturation as a predominant mechanism of enhanced absorption of poorly water-soluble drugs in many examples of LBFs (Gao and Morozowich 2006; Yeap et al. 2013
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