Development and Optimisation of a Novel Composit Delivery System to Improve Drug Solubility

Abstract

Poor drug solubility can limit drug permeability and bioavailability. Therefore, this research focused on utilising polymeric and lipid excipients to increase the apparent aqueous solubility of poorly soluble drugs.

Initial work investigated the impact of self-assembling amphiphilic polymers on the solubility of a hydrophobic molecule, ciclosporin. Thereafter, the effect of phospholipids on drug solubility was tested due to their possible physiological healing properties. The polymeric systems produced the highest drug solubility; however, the two materials were combined due to the potential clinical benefits of phospholipids.

Combining amphiphilic polymers with phospholipids produced a synergistic improvement in ciclosporin solubility greater than that expected from combining the polymeric and phospholipid formulations. The significant solubility improvement was suggested to be due to the formation of a novel particulate system as inferred by solubility values, particle size, polydispersity index, electron miscopy, viscosity, and differential scanning calorimetry measurements. Combining phospholipids with polymeric aggregates potentially led to the insertion of phospholipids into the polymeric aggregates, increasing the hydrophobicity of the core and the space available for hydrophobic drug loading. The novel particulate system was tested for ocular drug delivery by an in vitro permeability study through human corneal cells which demonstrated high permeability. The new system was then applied to tacrolimus, which also exhibited a synergistic solubility improvement.

Finally, the novel system was tested on carbamazepine, which did not show a synergistic improvement in solubility but an additive effect of the polymer and lipid, possibly because carbamazepine did not utilise the increased hydrophobic core but instead interacted with the exterior regions of the novel system.

Date of Award	Oct 2024
Original language	English
Awarding Institution	Aston University
Supervisor	Afzal-Ur-Rahman Mohammed (Supervisor) & Craig Russell (Supervisor)