Fundamental Aspects of Lipid-Based Excipients in Lipid-Based Product Development

Lipid-based drug delivery systems (LBDDS) are formulations consisting of drugs dissolved or suspended in the lipid excipients. LBDDS have been extensively explored for delivering lipophilic drugs, wherein lipids maintain the drug in the solubilized form. LBDDS are usually formulated by the dissolution of the drug in the molten mixed lipids and emulsified with water to form a stable lipid system [3]. Solubility screening is most often performed for determining the best lipid excipients for a given drug. Surfactants are used to stabilize the lipid particles by reducing surface free energy or the interfacial energy of the solid particles, thus inhibiting aggregation. Lipid excipients also promote drug partitioning within the skin epidermal lipids and thus accelerate the penetration of drugs through and within human skin. Physicochemical properties and absorption mechanism of the lipids make them different from other classes of carriers leading to substantial cost saving and availability to reach the market.

In this review, we exhaustively cover the lipids excipients useful in formulation development with physicochemical and biochemical behaviour, along with the computational simulations in solubility prediction, phase behaviour, drug absorption and regulatory perspective. Lipid excipients are mainly categorized as triglycerides (TG), mixed glycerides and polar oils, water-soluble and insoluble surfactants, co-solvents, and other additives. Ethanol, propylene glycol, glycerol, and polyethylene glycols-400 (PEG-400) are the commonly used co-solvents along with lipid excipients. Surfactants of intermediate hydrophilic-lipophilic balance (HLB) (8–12 lipid excipients, water-insoluble surfactants) that shows adsorption at the oil-water interfaces are available commercially. The lipid-based synthetic surfactant (including non-ionic surfactants), e.g., PEG-40 Hydrogenated castor oil, PEG-60 Hydrogenated castor oil, Polyoxyl 35 hydrogenated castor oil, Polyoxyethylene (20) sorbitan monolaurate and Polyoxyethylene sorbitan monooleate, Glyceryl monooleate, Caprylocaproyl macrogol-8 glycerides, Oleoyl polyoxyl-6 glycerides, and Linoleoyl polyoxyl-6 glycerides are widely used lipid excipients. The water-insoluble surfactant (Propylene glycol monocaprylate, Propylene glycol monolaurate, and Polyglyceryl-3 dioleate) and water-soluble surfactant (Polyoxyl stearate, Polyoxyethylene lauryl ether) has been widely used in the lipid-based formulations.