Charitini Volitaki

Charitini has a degree in Pharmacy from National and Kapodistrian University of Athens. During her diploma thesis, she investigated the effect of different novel preparations on wound healing in vivo. Later she obtained her MSc in Pharmaceutics at UCL School of Pharmacy, completing her thesis on ibuprofen-loaded electrospun nanofibers for sustained release formulation for peripheral nerve regeneration. Afterwards she worked as a formulation scientist for one year at Aptuit, an Evotec company.  She is currently a CDT PhD student at UCL, working on formulation of poorly soluble drugs as amorphous solid dispersions to enhance bioavailability using a novel mixed carrier approach.

PhD Project Title: Formulating poorly soluble drugs as amorphous solid dispersions to enhance bioavailability; a novel mixed carrier approach

Supervisor: Dr Asma Buanz

Oral delivery of drugs is the most common and convenient route owing to ease of administration, high patients compliance and flexibility of dosage form design.  Solubility of active pharmaceutical ingredients (APIs) is key in achieving the desired bioavailability for medicines administered by this route.  Most new APIs have low solubility (almost 40% of approved drugs and 90% of new ones in the discovery pipelines are poorly water-soluble), which leads to low dissolution and limits absorption.  Among the approaches to improve solubility, converting crystalline drugs into amorphous is one of the most promising.  Amorphous drugs are inherently physically and chemically instable (due to the high internal energy) and they tend to crystalline during storage and dissolution to reach the lower energy level.  Effective strategies are utilised to kinetically stabilise amorphous APIs, while retaining the solubility advantage.  One of those strategies has been the development of amorphous solid dispersions (ASDs) products.  Mesoporous silica nanoparticles (MSNs) have become a new generation of inorganic platforms for drug carriers for oral delivery.  MSNs have been investigated as a potential carrier to increase solubility and dissolution rate of poorly water-soluble drugs.  MSNs are able to physically stabilise the amorphous nature of the loaded drug.  However, enhanced dissolution of the drug at immediate release formulations results in supersaturation of the media.  Supersaturated solutions favour crystallisation thus fast precipitation of the drug to a more stable crystal form may be risky for the absorption.  The incorporation of excipients that delay or inhibit precipitation would be a successful strategy to maintain supersaturated concentrations and achieve higher bioavailability.

The aim of this PhD project is to utilise a mixed carrier approach to prepare drug delivery systems that will be able to enhance the bioavailability of the BSC class II and IV drugs.  Loading of ASD in polymeric matrix in MSNs will enable the prevention of crystallisation and precipitation of the amorphous drug from the supersaturated intestinal media during dissolution for BSC class II drugs, exploiting the Spring and Parachute approach.  Moreover, the combination of the ASD and MSNs will further stabilise the amorphous drug. An important aspect of understanding the stabilisation characteristics of ASD and MSNs requires rigorous study of the physical stability of the drug in these systems as well as the nanodistribution of the components in them.  Key techniques to achieve that will include simultaneous synchrotron X-ray diffraction and differential scanning calorimetry (SXRD-DSC), Raman microscopy and TOF-SIM chemical imaging.