Dry Powders for the Delivery of Biopharmaceuticals to the Nose

Traditionally, drugs delivered to the nose have been formulated as liquids. However, the delivery of a dry powder to the nose can bring several advantages: improve chemical and microbiological stability, prolong residence time, enhance systemic bioavailability, allow for a wide range of doses, facilitate the formulation of poorly water-soluble compounds, potantially target brain delivery by exploiting neuronal pathways to bypass the blood brain barrier, avoid incompatibility issues between drug and excipient and, especially, allow for room temperature storage bypassing cold chain.
Even though micronization and blending can be employed to product intranasal powders, spray drying and freeze drying are the most used techniques when it comes to biopharmaceuticals.
An example of this is the commercialized glucagon intranasal powder where the 29 amino acid peptide was freeze-dried to overcome stability issues of the liquid injectable formulation. The addition of enhancing excipients improved glucagon bioavailability by intranasal delivery to 28% from negligible bioavailability of glucagon alone. In this presentation, we will firstly discuss the reformulation of leuprolide, a 9-residue peptide analogue of gonadotropin-releasing hormone that is used to treat central precocious puberty, from its injectable form to an intranasal powder. Freeze drying and spray drying were both investigated as manufacturing processes, following a similar strategy to that used to produce the marketed product. The powders manufactured were then tested to assess their processability, suitability for intranasal administration and their delivery performance from a nasal device.
Other two examples will be then discussed on the use of alternative manufacturing technologies to produce intranasal powders. Particularly, thin-film-freezing was evaluated for the development of a mucoadhesive vaccine powder and for the intranasal delivery of a human-derived monoclonal antibody (mAb). In detail, a model vaccine that contains liposomal monophosphoryl lipid A, QS-21 adjuvant and ovalbumin (OVA) as a model antigen was dried in the presence of a mucoadhesive agent. Different powders were manufactured and the lead candidate was then selected for integrity, in vitro mucoadhesion and spray properties characterization. The final example will show the formulation of a mAb as nasal powder and its in vitro deposition pattern using 3D-printed nasal casts.
These case studies report concrete examples of how a nasal powder comprising a biomolecule can be developed, manufactured and processed and which in vitro/in vivo testing are carried out to assess the delivery.