Current global vaccination programs are challenged by costs associated with vaccine cold chain storage and administration. A solid, thermally stable oral dosage form for vaccines would alleviate these costs but is difficult to produce due to general vaccine instability and the complication of bypassing the gastric barrier. We developed a novel consecutive spray drying method that is suitable for use with biologics and employs Eudragit L100 polymer as the enteric coating. More specifically, in step 1, recombinant replication deficient human type-5 adenovirus and vesicular stomatitis virus were encapsulated by spray drying with sugars from a water solution, and in step 2, the microparticles from step 1 were suspended in ethanol with Eudragit and spray dried again. Up to 25% of the starting material was fully encapsulated within the enteric coating, and encapsulation efficiency was largely dependent on spray gas flow rate and the solids concentration in the feed. After step 2, the coated vaccine–sugar particles maintained their thermostability and were slightly larger in size with a rugous surface morphology compared to the particles produced in step 1. The coated particles retained viral vector activity in vitro after 15 min incubation in 1 M HCl (simulating the stomach environment) and anhydrous ethanol (to dissolve the Eudragit outer shell). The production of dry, orally administered vaccine particles from consecutive spray drying offers the potential to remedy a number of vaccine storage, transportation, and administration limitations.

Conclusions

Consecutive spray drying was used to prepare a thermally stable dry powder vaccine with an enteric coating; two viral vectors in separate excipient matrices were demonstrated. SEM, fluo- rescence microscopy, and particle sizing showed that after coating, the particles were larger and contained multiple vaccine−sugar microparticles in an uneven coating. Smaller Eudragit-only particles were a byproduct of the processing method, though future optimization may reduce their numbers. The overall encapsulation efficiency was low but could be improved by adjusting the spray drying process parameters. For example, faster drying and adding more coating material led to better encapsulation. Most importantly, retained viral activity was demonstrated for these coated vaccine powders after incubation in acidic conditions that simulated the gastric barrier. The potential for dried vaccine powders to alleviate cold chain storage needs is already notably promising in the literature, and introducing new coating methods such as the consecutive approach opens up the possibility of moving away from injection-based vaccine administration toward a new class of orally administrated vaccines.

More