Dr Richard Johnson, Chief Scientific Officer, Upperton Pharma Solutions
Drug products containing active biological ingredients form one of the most important and fastest-growing sectors of the pharmaceutical industry. These biologics include a wide range of large, complex molecules including protein and peptide products (such as monoclonal antibodies), through to more complex moieties including vaccines and oligonucleotides incorporated into lipid-based delivery vehicles.
Most biologics are formulated and administered to the patient in aqueous dosage forms but quite often this presents a stability challenge which results in limited shelf life, with storage requiring either frozen or refrigerated conditions. Often the only way to overcome this is to develop a dry powder formulation that is inherently more stable.
Freeze drying is the traditional process of choice for creating dry powder biologics but it suffers from several technical challenges resulting in lengthy drying processes over several days with significant energy and equipment costs. These challenges have meant that there is now a growing interest in alternative technologies for creating dry powder dosage forms.
Several experimental technologies - such as spray freeze drying, thin-film freeze drying and supercritical fluid drying – have generated interesting results but only spray drying has the existing capacity to be considered a viable option for the scale-up and manufacture of commercial-scale dry powder biologics.
There are already examples where spray-dried biologics have been incorporated into an aseptic dosage form and whilst this list is relatively small, there are a considerable number of spray-dried biologics in clinical development that are expected to achieve approval in the coming years.
In a recent case study, Upperton demonstrated the ability of spray drying to stabilize a large (mwt 66kDa) soluble, globular protein recombinant human albumin (rHA). In this study, rHA was formulated and either spray-dried or freeze-dried to create dry powder products. The resulting spray dried powder was far easier to handle and was shown to have near identical physical and stability properties to the formulation that was created using freeze drying.
Spray drying is a useful technology for producing dry powder formulations not only of proteins but also larger biological entities such as vaccines and nanoparticulate liposomal structures. This is potentially useful when considering the formulation of oligonucleotides such as mRNA which require a relatively large liposomal carrier to carry it across the target cell membrane and subsequently clear endosomal capture. Indeed in many instances, these liposomal structures cannot survive the physical effects of freezing required during freeze drying.
In a recent study, the team at Upperton investigated whether spray drying was capable of producing dry powder virosomal (liposomal based) formulations since freeze drying had been shown to cause significant damage to the delicate structures.
The delicate, waterfilled liposomal vaccines were spray dried using a range of drying temperatures and in all cases, the spray dried powders produced could be reconstituted in water to maintain the same particle size as before spray drying.
Closer analysis of the surface antigens using HPLC and ELISA techniques confirmed that all of the influenza surface antigens and the critical P-1 and gp41 antigens remained unchanged after spray drying as well as the associated adjuvant.
Our latest white paper “Spray Drying Biologics: An Alternative To Freeze Drying” sheds more light on how spray drying offers an alternative, more cost-effective route for creating dry powder biologics with some intriguing physical advantages created by this fast-emerging process.
