Experts from Capsugel and Catalent discuss the rationale of using lipid-based formulations to improve the oral bioavailability of poorly soluble drugs

Moderated by Adeline Siew, PhD the oral bioavailability of a drug via several mechanisms, with the unique potential to address both physicochemical and biological obstacles to systemic exposure. It is, therefore, appropriate to describe these mechanisms in relation to the fate of a lipid-based formulation in the gastrointestinal (GI) tract: Stomach. Lipid-based formulations containing the drug, either dissolved or suspended, are typically administered via hard or soft capsules. Following rupture and disintegration of the capsule shell in the stomach, the formulation mixes with gastric fluid to an extent that is governed by formulation composition and stomach contents. In the fasted state (which is usually more challenging for poorly soluble drugs than fed-state conditions), those formulations containing a mixture of oil and surfactant(s) will self-emulsify before entering the small intestine—the primary site of drug absorption. Small intestinal lumen. Here, a high dissolved drug concentration at the intestinal wall will promote passive drug diffusion across the enterocyte membrane. For a poorly soluble drug, enabling technologies are required to increase solubility and dissolution so that a high dissolved concentration that drives intestinal absorption can be attained. This may be achieved via lipid-based formulations, wherein the potential to administer the drug predissolved in the formulation matrix is such that dissolution can be bypassed altogether, while the lipidic components of the formulation (dispersed and/or digested) mix with endogenous bile salts and phospholipids to form a range of colloidal species that increase drug solubility and present the drug in a well-dispersed and readily absorbable form. Small colloidal species formed by lipidic excipients and endogenous solubilizers will also enhance drug transport through the unstirred water layer, which can be slow and potentially limiting to absorption when the drug is lipophilic. Enterocyte. Lipid-based formulations may also impact post-absorption events to improve bioavailability of drugs that are subject to: Experts from Capsugel and Catalent discuss the rationale of using lipid-based formulations to improve the oral bioavailability of poorly soluble drugs.