The Power of Formulation : a Journey from Pharmaceutics to Biochemical Engineering

The power of formulation: a journey from Pharmaceutics to Biochemical Engineering

Raquel Fernández García

Formulation involves designing and producing drug delivery systems where drugs and excipients are combined in specific ways to achieve desired functionality, improving stability and performance. This is a core principle of classical Pharmaceutics, where amphotericin B (AmB) has been widely investigated. Research interest in this drug lies in its antifungal and antiparasitic efficacy, despite its current unavailability in patient-friendly forms. Thus, developing topical or oral AmB formulations represents a therapeutic alternative to parenteral presentations. In this work, formulations based on liposomes were developed to enhance the transdermal permeability of AmB, as well as fixed-dose combinations for oral administration of AmB with other antimicrobials. The optimisation of these topical and oral AmB formulations, using a design of experiments (DoE) approach, resulted in promising therapeutic alternatives to conventional antifungal and antiparasitic treatments, offering a very favourable benefit/risk balance.

The same formulation principles explored in Pharmaceutics have also been applied in Biochemical Engineering to develop formulations tailored to enhance bioproduct stabilisation. Recombinant adeno-associated virus (AAV) vectors have gained rapid popularity as delivery vehicles for gene therapy due to their reduced inflammatory profile. AAV administration can require high drug product concentrations (>10¹³ viral genomes/mL). Such high vector concentration may induce aggregation and consequently cause undesirable immune responses. Drug product formulations of approved AAV products to date are comprised of up to five different categories of excipients.

Here we aimed to expand the AAV formulation toolbox by exploring twenty excipients within six categories for enhanced formulation compositions. To this end, we leveraged a systematic DoE approach which included three rounds of DoE investigations. Industrially relevant AAV feed material was the source of purified vector for excipient screening and optimisation. The six excipient categories explored included buffer types, tonicity agents, surfactants, cryoprotectants and stabilising compounds which are novel to AAV formulations. Excipient effects and interactions were evaluated based on thermal stability as measured by differential scanning fluorometry (DSF), viral particle size by dynamic light scattering (DLS) and ultrafiltration/diafiltration recovery via size exclusion chromatography (SEC-HPLC).

Speaker: Raquel Fernández Garcia (PostDoc Researcher, Faculty of Pharmacy, University of Nottingham).