Co-amorphous drug-lecithin systems – bridging the gap between amorphous solid disperions and lipid based drug delivery
The purpose of the project is to investigate the potential use of lecithin1) as co-former to develop co-amorphous solid dispersions for a range of poorly water-soluble drugs.2)3)4)5)6) Co-amorphous drug lecithin systems are envisaged as both, amorphous solid dispersions and lipid-based drug delivery systems. As such, it is hypothesized that they form an excellent basis both for poorly water-soluble lipophilic compounds (“grease ball” molecules) and poorly water-soluble compounds with high melting points (“brick dust” molecules), and thus may be broadly applicable. Emphasis will be placed on using readily available GRAS status lecithins as well as a range of drugs, covering a large chemical space. For the first time, different preparation methods for these systems will be investigated, including melt-based, solvent-based, and mechano-chemical activation-based methods. Additionally, the use of co-amorphous drug lecithin systems as a new source of drug-form to be added to lipid-based drug delivery systems (self nano-emulsifying drug delivery systems – SNEDDS) will be investigated, which is hypothesized to be especially beneficial for “brick dust” molecules, that currently largely not suitable for delivery in lipid-based drug delivery systems due to poor oil solubility. The studies will range from preparation, to physical-chemical characterization, to dissolution, solubility and absorption testing, using in vitro gastric and intestinal lipolysis, to in vivo studies in rats.
Taken together, the envisaged study has the potential to establish co-amorphous drug lecithin systems as a viable and broadly applicable formulation option for poorly water-soluble drugs
Benefit for the community
The study will contribute to the faster and more efficient development of poorly water-soluble drugs. It will help establishing a new formulation strategy, with potentially very broad applications to a large range of drugs. This ultimately will lead to better medicines being available for patient faster.
Molecular insights into the formation of drug-monoacyl phosphatidylcholine solid dispersions for oral delivery
Eur. J. Pharm. Sci. 108, 93-100
A dynamic in vitro permeation study on solid mono- and diacyl-phospholipid dispersions of celecoxib
Eur. J. Pharm. Sci. 127, 199-207
Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine
Eur. J. Pharm. Sci. 74, 11-17
Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs: Investigation Into Celecoxib Incorporation and Solubility-Vitro Permeability Enhancement
J. Pharm. Sci. 105, 1113-1123
|J Pharm Sci|
Phospholipid-based solid drug formulations for oral bioavailability enhancement: A meta-analysis
Eur. J. Pharm. Sci. 80, 89-110