Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems

Abstract

Poorly water-soluble drug candidates are becoming more prevalent. It has been estimated that approximately 60-70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration. Formulation scientists have to adopt various strategies to enhance their absorption. Lipidic formulations are found to be a promising approach to combat the challenges. In this review article, potential advantages and drawbacks of various conventional techniques and the newer approaches specifically the self-emulsifying systems are discussed. Various components of the self-emulsifying systems and their selection criteria are critically reviewed. The attempts of various scientists to transform the liquid self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption, spray drying, lyophilization, melt granulation, extrusion, and so forth to formulate various dosage forms like self emulsifying capsules, tablets, controlled release pellets, beads, microspheres, nanoparticles, suppositories, implants, and so forth have also been included. Formulation of SEDDS is a potential strategy to deliver new drug molecules with enhanced bioavailability mostly exhibiting poor aqueous solubility. The self-emulsifying system offers various advantages over other drug delivery systems having potential to solve various problems associated with drugs of all the classes of biopharmaceutical classification system (BCS).

Figure 1

Schematic diagram of intestinal drug transport from lipid-based formulations via the portal and the mesenteric lymphatic routes. (A) Increased membrane fluidity facilitating transcellular absorption. (B) Opening of tight junctions to allow paracellular transport. (C) Inhibition of P-gp and/or CYP450 to increase intracellular concentration and residence time. (D) Stimulation of lipoprotein/chylomicron production. ABL: aqueous boundary layer; D: drug; D−: ionized drug substance; FA: fatty acid; LCFA: long chain fatty acid; ME: microemulsion; MG: monoglyceride; SEDDS: self-emulsifying drug delivery system; TG, triglyceride; TJ, tight junction.

Figure 2

Schematic presentation of the mechanism happening during addition of water in SEDDS. (a) Water droplets in continuous oil phase; (b) water cylinders in oil; (c) lamellar structures; (d) oil droplets in continuous phase.