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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
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815322/ https://www.ncbi.nlm.nih.gov/pubmed/33035539 http://dx.doi.org/10.1016/j.xphs.2020.09.047 |
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author | Kumar, Prashant Pullagurla, Swathi R. Patel, Ashaben Shukla, Ravi S. Bird, Christopher Kumru, Ozan S. Hamidi, Ahd Hoeksema, Femke Yallop, Christopher Bines, Julie E. Joshi, Sangeeta B. Volkin, David B. |
author_facet | Kumar, Prashant Pullagurla, Swathi R. Patel, Ashaben Shukla, Ravi S. Bird, Christopher Kumru, Ozan S. Hamidi, Ahd Hoeksema, Femke Yallop, Christopher Bines, Julie E. Joshi, Sangeeta B. Volkin, David B. |
author_sort | Kumar, Prashant |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7815322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78153222021-02-01 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 Kumar, Prashant Pullagurla, Swathi R. Patel, Ashaben Shukla, Ravi S. Bird, Christopher Kumru, Ozan S. Hamidi, Ahd Hoeksema, Femke Yallop, Christopher Bines, Julie E. Joshi, Sangeeta B. Volkin, David B. J Pharm Sci Research Article 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. Elsevier 2021-02 /pmc/articles/PMC7815322/ /pubmed/33035539 http://dx.doi.org/10.1016/j.xphs.2020.09.047 Text en http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Kumar, Prashant Pullagurla, Swathi R. Patel, Ashaben Shukla, Ravi S. Bird, Christopher Kumru, Ozan S. Hamidi, Ahd Hoeksema, Femke Yallop, Christopher Bines, Julie E. Joshi, Sangeeta B. Volkin, David B. 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815322/ https://www.ncbi.nlm.nih.gov/pubmed/33035539 http://dx.doi.org/10.1016/j.xphs.2020.09.047 |
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