Release characteristics of microspheres prepared by co-spray dryingActinobacillus pleuropneumoniaeantigens and aqueous ethyl-cellulose dispersion

Abstract

Using formalin inactivated Actinobacillus pleuropneumoniae antigens and aqueous ethylcellulose dispersions, microspheres of oral vaccines were developed by a co-spray drying process. The present study attempted to determine whether the dosage formulations of microspheres could form enteric matrices. To assess the enteric characteristics, an in vitro dissolution test was performed with the AQ6-AP microspheres; 95% of the A. pleuropneumoniae protein was released within 3 h at pH 7, but there was no release at pH 1.5. The scanning microscopy revealed that the surface structure of AQ6-AP microspheres became porous at neutral pH. The SDS-PAGE analysis showed that the release rate of proteins from the microspheres was pH dependent not only for the AQ6-AP formulation but also when antigens of A. pleuropneumoniae were replaced with porcine serum. The results suggest that the A. pleuropneumoniae antigens were entrapped in the AQ6 microspheres under the acidic conditions. In a mouse model, oral immunization with AQ6-AP microspheres containing A. pleuropneumoniae evoked systemic IgG and mucosal IgA responses against A. pleuropneumoniae antigens. Thus, the present method may further provide an opportunity to develop oral vaccines and mucosal immunity.

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

“…For this, it is not surprising that the spray-drying of diverse types of vaccines has gathered the deep interest of various research groups. [71,[117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135] In Figure 3, we present the chronological trends of the studies in the spray-drying of protein pharmaceuticals. We can observe an extensive research of peptide hormones during 2002-2011, and their numbers dwindling slightly in recent years.…”

“…[132] Ammonium carbonate, a known pore former agent, has been used to produce aerosolisable particles of octreotide acetate. [85] Finally, magnesium stearate has been applied to the production of microspheres of an oral vaccine of Actinobacillus pleuropneumoniae, [124] probably as agglomeration preventing agent. [167]…”

“…Ethyl cellulose and HPMCAS have been used in combination to investigate the possible production of oral vaccines for melanoma and Actinobacillus pleuropneumoniae. [122][123][124] Particularly HPMC, that has been studied in-depth, showed that when used alone, it can migrate to the surface of spray-dried droplets, coating proteins in-situ and exerting a beneficial protective effect on biomolecules. [106] Moreover, the same study also showed that HPMC produced irregularly surfaced particles that could have an advantage in terms of powder flowability and provide the sustained release of a drug.…”

“…[188,189] Rotatory atomization nozzles have been used at larger scales to evaluate the drying behavior of alcohol dehydrogenase encapsulated in trehalose matrices [75] and to successfully produce microspheres of Actinobacillus pleuropneumoniae antigens intended for oral vaccination. [124] 6.1.5. Low-pressure ultrasonic nozzle These types of nozzle use a hybrid principle between ultrasonic and twin-fluid atomization.…”

“…Nonetheless, it is important to understand if the processes developed at smaller scales are transferable to larger ones. Obviously, the commercialization of products such as Exubera V R , Trelstar V R LA, Somatuline V R LA, and Raplixa V R , as well as other additional evidence in literature show that dry powder inhalers, wound therapies, vaccines [124,144] and injectables [34,36,82] of proteins can be successfully produced at larger scales. A potential difference between spraydryers across scales, due to differences in equipment and throughput, is the particle size of the obtained powders.…”