By Shaukat Ali and Robert Garmise
Many new drugs are challenging to formulate due to low and erratic bioavailability and often require nonconventional, enabling formulation technologies. These encompass drugs with both solubility and permeability-limited absorption. Quite often, however, the formulator is contemplating a) which technology to use and why depending on the biopharmaceutical properties of the compound and mechanistic aspects of solubility and permeability enhancement, and b) what specific formulations and dosage forms to consider for expeditious feasibility studies and proof of concept in humans.
Lipid-based drug delivery systems (LbDDS), in the form of self-emulsifying/microemulsifying drug delivery systems (SEDDS/SMEDDS) and related systems, are a useful and validated approach to effectively formulate and deliver these challenging molecules. The presence of both polar head groups and apolar hydrophobic chains (fatty acids) in the lipid molecule enable solubility enhancement of a wide range of drugs and also provide a perfect opportunity for lipid-drug interactions and site-specific delivery. Articles in The AAPS Journal theme Oral Absorption-Enhancing Formulations: Manufacture Technologies and Challenges have touched upon leveraging these systems. There is also a tremendous amount of recently published and ongoing research to elucidate the mechanisms by which these aggregates self-emulsify into SEDDS/SMEDDS to drug/lipid particulates (or droplets); how the lipid droplets are controlled by the type and amounts of lipids/surfactants; and how these droplets get carried through the intestinal milieu for lymphatic absorption to help increase the bioavailability of drugs. Examples of drugs approved in SEDDS/SMEDDS are Amprenavir, Ritonavir, Ritonavir/Lopinavir, Saquinavir, Tipranavir, Cyclosporine, and Asunaprevir amongst others. In LbDDS, the drug is often administered in solution or dispersed form utilizing diverse lipid excipients that provide intestinal drug stabilization, solubilization, and permeation enhancement, thus facilitating a faster and improved absorption of even the most challenging drugs.
To learn more about oral LbDDS and their roles to effectively enhance drug solubility and permeability in order to protect and stabilize drugs prone to pH or enzymatic-catalyzed hydrolysis, formulations technologies, and best practices for successful drug development, we invite you to attend the upcoming AAPS workshop Enabling the Development of Oral Therapeutics with Innovations in Lipid Formulation Technologies, September 19–20, in Plainsboro, N.J. Scientists attending the workshop will learn how to create the SEDDS/SMEDDS as a viable oral pharmaceutical dosage form to attain supersaturation in the gastrointestinal (GI) tract of poorly soluble compounds and promote paracellular transport and absorption of poorly permeable drugs. An understanding of these mechanisms is important for proper design of lipid formulation to overcome low bioavailability limited by poor solubility and/or permeability, to mitigate food effects, and to eliminate negative effects of low pH in the stomach. Lessons learned at this workshop can be rationally applied for timely development of new molecular entities (NMEs) and product line extensions (PLEs). Do not miss this opportunity to learn directly from thought leaders across the industry, academia, and government, and rationally apply acquired knowledge to your specific poorly-soluble and/or poorly permeable compounds.