A phospholipid-functionalized calcium carbonate based drug delivery system to improve the bioavailability of poorly water-soluble drugs
Maryam Farzan (PhD fellow sponsored by the PRC) and Dr. Gabriela Québatte – University Basel/Switzerland
Due to the introduction of an increasing number of low water-soluble drug candidates, there is a rising demand for novel oral drug delivery systems to formulate poorly water-soluble drugs. Phospholipids can be used to improve dissolution of lipophilic drugs and to enhance their absorption from the gastrointestinal tract after oral administration. They are biocompatible and well established as pharmaceutical excipients. Oral liposomes specifically are a promising drug delivery system for enhancement of bioavailability of low-soluble drugs. However, the use of oral liposomes for oral drug delivery is limited owing to the formulation and stability issues associated with these formulations. Proliposomes as solid formulations that produce liposomes upon hydration, offer a solution for these issues. In this study, we aim to produce a solid formulation with a combination of phospholipids (PL) and functionalized calcium carbonate (FCC). This inexpensive inorganic material is characterized by a highly porous surface and internal structure. It is biocompatible, non-toxic, and has high loading efficiencies.
In this study, phospholipids will be immobilized within the pores of the inorganic carrier FCC. This new formulation will readily reconstitute into a liposomal formulation. We study the mechanism of formation of these liposomes and their characteristics in various media mimicking the conditions of the GI tract. Furthermore, the influence of the concentration of the phospholipids on the interaction of poorly water-soluble drugs with FCC will be studied.
Benefit for the community
A novel PL-FCC excipient will be biocompatible, inexpensive, and possible to scale-up for production of oral dosage forms in conventional ways. Thus, drug candidates for liposomal formulations that are so far excluded from oral formulations can be reassessed.
A one-step loading process for phospholipids and a model low soluble drug in the internal porous structure of FCC was employed and a reliable method for accurate characterization of the loaded carrier was developed. The mechanism of the formation of liposomes from the formulations in the GI conditions was found to be different in the acidic condition of the stomach compared to media with neutral pH. The formulations achieved significantly faster dissolution for a low-soluble drug in the gastric conditions. We identified the parameters that influence the performance of these formulations and found that a trade-off between the positive effects of the phospholipids and the porous carrier exists in the combination formulations.
Spontaneous in situ formation of liposomes from inert porous microparticles for oral drug delivery
Loading of Porous Functionalized Calcium Carbonate Microparticles: Distribution Analysis with Focused Ion Beam Electron Microscopy and Mercury Porosimetry
Pharmaceutics 11, 32