In Vitro Characterisation of Octreotide Microspheres Formulated for Nose to Brain Delivery
Reanne Beaird1, Elisavet Dimosthenous1, Katie Bamsey2, Zoe Rees2, Rhian Davies2, Irene Rossi1
1Nanopharm Ltd, an Aptar Pharma Company, Grange Road, Cwmbran, NP44 3WY, United Kingdom
2Biodexa Pharmaceuticals, Caspian Way, Cardiff, CF10 4DQ, United Kingdom
Summary
Octreotide is a metabolically stable analogue of a somatostatin, a potent inhibitor of secretory processes, and has promising results against the neurological condition idiopathic intracranial hypertension when delivered subcutaneously. Delivery of octreotide intranasally to the brain by bypassing the blood brain barrier and targeting the central nervous system through the olfactory region of the nasal cavity can increase its efficacy. Biodexa Pharmaceuticals have developed Q-SpheraTM octreotide loaded poly(lactic-co-glycolic acid) (PLGA) microspheres that could be promising for nose-to-brain delivery by increasing residence time, controlling the release of the encapsulated drug and reducing systemic side effects. The aim of this study was to formulate and assess the suitability of delivering the Q-SpheraTM for nose-to-brain with Aptar VP7 coupled with 232-NE actuator. A suitable formulation for nasal delivery was prepared as indicated by the pH value of 5.05 and osmolality value of 491 mOsm/kg. No effect of shear stress on the microspheres was observed with the same PSD obtained before and after spraying. The microsphere formulation displayed a large median droplet size (134 µm) due to its higher viscosity (3.7 cps) in comparison to an octreotide nasal solution (66 µm). Despite the larger droplet size, the in vitro nasal cast deposition study indicated a significantly higher deposition in the nasal region of interest, the olfactory area, for the microspheres’ nasal formulation, due to the narrower plume emitted. These results indicate that the microspheres can be successfully formulated for nasal administration showing spray characteristics that are suitable for nose-to-brain delivery.