Lipid excipients offer a unique combination of benefits
Poor solubility, poor permeability, and pre-systemic elimination are factors that can limit absorption of some drugs. Lipid excipients have the capability to overcome these hurdles and enhance oral bioavailability through different mechanisms.
Increase drug solubility
Poorly water-soluble drugs are generally soluble in lipid excipients, as revealed by the abundant scientific literature on lipid-based formulations.
Maintain drug solubilization throughout digestion
Upon action of enzymes and bile salts, the lipid-based formulation is digested and transformed in a series of colloidal structures: vesicles, mixed micelles, and crystalline lipid phases. They contribute to maintaining the drug in solubilized state throughout the digestion process. Ultimately, fatty acids, monoglycerides and drug partition out of the micelles, and are absorbed.
Mitigate food effect
Ingestion of a lipid-based formulation is sufficient to trigger the release of bile and lipases, in the same manner and extent as it occurs with a fat-containing meal. The difference between fasted and fed state is minimized and food effect can be overcome.[/vc_column_text][/vc_column][/vc_row]
Increase intestinal permeability
Medium-chain fatty acids (C8-C10) are known to facilitate intestinal absorption of poorly permeable drugs via:
Transcellular uptake due to a membrane fluidization effect.
Paracellular transport due to the reversible opening of tight junctions.
Target lymphatic transport
Two prerequisites to promote lymphatic absorption:
As a general rule, the drug should be highly lipophilic (Log P > 5) and soluble in triglycerides
(>50 mg/g).
The formulation must contain unsaturated long-chain fatty acids (C16-C18:1, C18:2) known to
facilitate lymphatic uptake via assembly of drug with lipoproteins in the chylomicrons.
Overview of Gattefossé excipients for oral bioavailability enhancement
Lipid-based formulations present the drug in a solubilized state in the gastro-intestinal tract. As such, the drug molecule solubility and stability in the excipients will dictate the formulation type. Formulation design and excipient choices are also influenced by considerations of other factors, such as emulsification capacity in the GI tract, behavior upon digestion, targeted route of drug absorption (lymphatic or systemic), and potential interactions of the drug with food. In all cases, careful selection of the lipid excipient(s) is necessary for increasing oral bioavailability.
Overview of Gattefossé excipients for oral bioavailability enhancement
LBF type II and III are known for enhanced solubilization capacity and auto-emulsification properties, hence referred to as Self Emulsifying Drug Delivery Systems (SEDDS).
Our self-emulsifying excipients are all-in-one systems enabling the preparation of:
Type II LBF: Labrafil® M 1944 CS or Labrafil® M 2125 CS
Type III LBF: Gelucire® 44/14, Gelucire® 50/13, Gelucire® 59/14 or Labrasol® ALF
Increase intestinal permeability
