Phospholipid based liquid-fill formulations for hard capsules
Phospholipids are well-established excipients for the parenteral delivery of poorly water-soluble drug.1)2) For this way of administration, they are employed for the formulation of liposomes (e.g., AmBisome®, Visudyne®) or as emulsifiers in colloidal fat emulsions for parenteral nutrition (e.g., Intralipid®, Lipofundin®) or as drug carriers (e.g., Stesolid®, Disoprivan®). Their use as major component in pharmaceutical formulations for peroral administration is much less frequent.
This project aims at widening the application area of phospholipids by identifying suitable phospholipid-based formulations as drug delivery systems for the liquid filling of hard capsules. The project systematically investigates different lipid compositions with respect to their miscibility, storage stability and dispersing properties in gastrointestinal fluids. Further, the compatibility with the liquid filling process and hard capsule materials is investigated. The incorporation capacity for poorly water-soluble drug substances is determined for different model drugs.
Benefit for the community
The successful project will lead to better options for the delivery of poorly water-soluble drug substances and will widen the scope of excipients used in lipid-based formulations.
In summary, it was established how to prepare phospholipid-based formulations with a high content of phosphatidylcholines. A comprehensive miscibility study led to thorough understanding about the miscibility of different phospholipids with fats and oils and the structures formed by the phospholipids. Several formulations easily dispersed in simulated intestinal fluids. Further, several phosphatidylcholine-based formulations exhibited appropriate viscosity and absence of stringing which should allow for liquid filling in hard capsules. The mixtures were compatible with hydroxypropylmethylcellulose (HPMC) hard capsules. The poorly water-soluble drugs fenofibrate, clofazimine, artemether and cannabidiol exhibited varying loading capacities in the formulations. The most promising carriers were mixtures with a high content of Miglyol 812.
Solubilizing excipients in oral and injectable formulations
Pharm. Res. 21, 201-230
Role of phospholipids in the oral and parenteral delivery of poorly water soluble drugs
J. Drug Delivery Sci. Technol. 21, 5-16
Suitability of phosphatidylcholine-based formulations for liquid filling in hard capsules
Eur. J. Pharm. Sci. 153, 105470
Self-dispersing formulations for the delivery of poorly soluble drugs - Miscibility of phosphatidylcholines with oils and fats
Eur. J. Pharm. Biopharm. 151, 209-219