dc.contributor.author | Kumar, Prashant | |
dc.contributor.author | Pullagurla, Swathi R. | |
dc.contributor.author | Patel, Ashaben | |
dc.contributor.author | Shukla, Ravi S. | |
dc.contributor.author | Bird, Christopher | |
dc.contributor.author | Kumru, Ozan S. | |
dc.contributor.author | Hamidi, Ahd | |
dc.contributor.author | Hoeksema, Femke | |
dc.contributor.author | Yallop, Christopher | |
dc.contributor.author | Bines, Julie E. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Volkin, David B. | |
dc.date.accessioned | 2022-01-11T17:25:47Z | |
dc.date.available | 2022-01-11T17:25:47Z | |
dc.date.issued | 2020-10-06 | |
dc.identifier.citation | Kumar, P., Pullagurla, S. R., Patel, A., Shukla, R. S., Bird, C., Kumru, O. S., Hamidi, A., Hoeksema, F., Yallop, C., Bines, J. E., Joshi, S. B., & Volkin, D. B. (2021). Effect of Formulation Variables on the Stability of a Live, Rotavirus (RV3-BB) Vaccine Candidate using in vitro Gastric Digestion Models to Mimic Oral Delivery. Journal of pharmaceutical sciences, 110(2), 760–770. https://doi.org/10.1016/j.xphs.2020.09.047 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32390 | |
dc.description.abstract | In this work, two different in vitro gastric digestion models were used to evaluate the stability of a live attenuated rotavirus vaccine candidate (RV3-BB) under conditions designed to mimic oral delivery in infants. First, a forced-degradation model was established at low pH to assess the buffering capacity of formulation excipients and to screen for RV3-BB stabilizers. Second, a sequential-addition model was implemented to examine RV3-BB stability under conditions more representative of oral administration to infants. RV3-BB rapidly inactivated at < pH 5.0 (37 °C, 1 h) as measured by an infectivity RT-qPCR assay. Pre-neutralization with varying volumes of infant formula (Enfamil®) or antacid (Mylanta®) conferred partial to full protection of RV3-BB. Excipients with sufficient buffering capacity to minimize acidic pH inactivation of RV3-BB were identified (e.g., succinate, acetate, adipate), however, they concomitantly destabilized RV3-BB in accelerated storage stability studies. Both effects were concentration dependent, thus excipient optimization was required to design candidate RV3-BB formulations which minimize acid-induced viral inactivation during oral delivery while not destabilizing the vaccine during long-term 2–8 °C storage. Finally, a statistical Design -of-Experiments (DOE) study examining RV3-BB stability in the in vitro sequential-addition model identified key formulation parameters likely affecting RV3-BB stability during in vivo oral delivery. | en_US |
dc.publisher | Wiley | en_US |
dc.rights | Published by Elsevier Inc. on behalf of the American Pharmacists Association. This is an open access article distributed under the terms of the Creative Commons CC-BY license. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Rotavirus | en_US |
dc.subject | RV3-BB | en_US |
dc.subject | Live virus vaccine | en_US |
dc.subject | Formulation | en_US |
dc.subject | Stability | en_US |
dc.subject | Oral delivery | en_US |
dc.title | Effect of Formulation Variables on the Stability of a Live, Rotavirus (RV3-BB) Vaccine Candidate using in vitro Gastric Digestion Models to Mimic Oral Delivery | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Kumar, Prashant | |
kusw.kuauthor | Pullagurla, Swathi R. | |
kusw.kuauthor | Patel, Ashaben | |
kusw.kuauthor | Shukla, Ravi S. | |
kusw.kuauthor | Bird, Christopher | |
kusw.kuauthor | Kumru, Ozan S. | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kuauthor | Volkin, David B. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1016/j.xphs.2020.09.047 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7815322 | en_US |
dc.rights.accessrights | openAccess | en_US |