Lipid-Based Drug Delivery Systems

Lipid-based drug delivery (LBDD) systems are well suited for poorly water-soluble, lipophilic, hydrophobic APIs. LBDDs comprise single or multiple excipients, forming oily formulations, self-emulsifying (SEDDS) and self-microemulsifying (SMEDDS) formulations, and micellar solutions.

Lipid-based formulations

They are categorized into four types on the basis of composition, dispersion, and digestion characteristics.

LFCS Type I formulations consist of lipophilic ingredients (oils) that are not dispersible in aqueous media. They act as solubilizers/carriers for highly lipophilic drug molecules (high log P) in the dosage form. On digestion they contribute to the micellization of lipophilic APIs and subsequent absorption mediated by fatty acids and monoglycerides.

LFCS Type II and Type III formulations are self-emulsifying systems consisting of water-miscible excipients with self-emulsifying and wetting properties. The extent of the resulting dispersions may vary depending on formulation components. Digestion of excipients leads to micellization of the lipophilic APIs and subsequent absorption mediated by fatty acids and monoglycerides.

LFCS Type IV systems contain little or no oil. They are mainly composed of water-soluble surfactants and hydrophilic cosolvents, capable of forming transparent micellar solutions on contact with aqueous or GI media. These formulations generally exhibit substantial solvent capacities that can be compromised upon dilution. Depending on the composition, the formulation may or may not be digestible, which also impacts drug solubilization and absorption.

Lipid excipients as self-emulsifying (SEDDS) and self-microemulsifying (SMEDDS) drug delivery systems

Self-emulsifying lipid formulations (SELFs) form emulsions upon contact with aqueous fluids without the need for mechanical or thermal energy.

The size of the dispersion depends on the composition of excipients in the formulation.

  • High-HLB polyoxylglycerides—Labrasol® ALF, Gelucire® 44/14 and Gelucire® 50/13—are good surfactants and contain a small fraction of glycerides. Their composition is water dispersible, forming microemulsions (LFCS Type III SMEDDS) upon contact with aqueous fluid.
  • High-HLB polyoxylethylene stearate—Gelucire® 48/16—is a pure surfactant with no glyceride fraction. It is able to form a micellar solution (LFCS Type IV formulation) upon contact with an aqueous fluid.
  • Lower-HLB polyoxylglycerides—Labrafil® M 1944 CS and Labrafil® M 2125 CS—have a higher proportion of glycerides and a lower concentration of free PEG, and they are less soluble in water. They spontaneously form emulsions (LFCS Type II SEDDS) in aqueous fluid.

Gattefosse SELF schematic representation

Excipient selection and formulation development

In some cases, a single excipient provides sufficient solubilizing power for the entire therapeutic dose. This can be the case with oily excipients (like Maisine® CC) with highly lipophilic APIs; self-emulsifying excipients like Labrasol® ALF, Gelucire® 44/14, or Gelucire® 50/13; and micellar systems like Gelucire® 48/16.  However, if two or more excipients are required to solubilize the therapeutic dose, a step-wise approach to formulation development is required: this includes miscibility assays and the construction of a ternary phase diagram.

Getting started and further learning

Selection of the right candidate excipients for formulation development depends on API properties and the therapeutic dose since the dosage form unit is designed to deliver the entire dose of the solubilized drug.

Gattefosse Bioavailability guidelines

in vitro characterization, including the lipolysis assay, are described in our Guidelines for Lipid-Based Formulations for Oral Bioavailability Enhancement, available from your local Gattefossé contact.

Remember: nothing beats one-to-one support in lipid-based formulation, so please don’t hesitate to contact us.

 

 

 

Lipid excipients or formulations for preclinical studies

A vehicle or formula intended for preclinical studies must allow adequate administration of the test compound with little or no effect on the test species. The vehicle or formulation must be suitable for the intended route of administration, maintain the stability of the active ingredient, and preferably, maximize the systemic bioavailability of the drug. Lipid excipients provide a solution to these challenges and have proven utility in preclinical studies. Further information is available from Gattefossé guideline

Guide for successful preclinical studies with Gattefossé excipients 2018 v1

Handling lipid excipients

Our lipid excipients are available as liquids, semisolids, and solids—each form requiring different handling procedures. Correct handling ensures excipient homogeneity and helps preserve quality. Excipient handling information is available from your local Gattefossé representative.