PMID- 28506515
OWN - NLM
STAT- MEDLINE
DCOM- 20190201
LR  - 20190201
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 36
IP  - 22
DP  - 2018 May 24
TI  - Combined semi-empirical screening and design of experiments (DOE) approach to 
      identify candidate formulations of a lyophilized live attenuated tetravalent 
      viral vaccine candidate.
PG  - 3169-3179
LID - S0264-410X(17)30602-3 [pii]
LID - 10.1016/j.vaccine.2017.04.086 [doi]
AB  - A combination experimental approach, utilizing semi-empirical excipient screening 
      followed by statistical modeling using design of experiments (DOE), was 
      undertaken to identify stabilizing candidate formulations for a lyophilized live 
      attenuated Flavivirus vaccine candidate. Various potential pharmaceutical 
      compounds used in either marketed or investigative live attenuated viral vaccine 
      formulations were first identified. The ability of additives from different 
      categories of excipients, either alone or in combination, were then evaluated for 
      their ability to stabilize virus against freeze-thaw, freeze-drying, and 
      accelerated storage (25 degrees C) stresses by measuring infectious virus titer. An 
      exploratory data analysis and predictive DOE modeling approach was subsequently 
      undertaken to gain a better understanding of the interplay between the key 
      excipients and stability of virus as well as to determine which combinations were 
      interacting to improve virus stability. The lead excipient combinations were 
      identified and tested for stabilizing effects using a tetravalent mixture of 
      viruses in accelerated and real time (2-8 degrees C) stability studies. This work 
      demonstrates the utility of combining semi-empirical excipient screening and DOE 
      experimental design strategies in the formulation development of lyophilized live 
      attenuated viral vaccine candidates.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Patel, Ashaben
AU  - Patel A
AD  - Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization 
      Center, University of Kansas, Lawrence, KS 66047, United States.
FAU - Erb, Steven M
AU  - Erb SM
AD  - Takeda Vaccines Inc., Cambridge, MA 02139, United States.
FAU - Strange, Linda
AU  - Strange L
AD  - Takeda Vaccines Inc., Cambridge, MA 02139, United States.
FAU - Shukla, Ravi S
AU  - Shukla RS
AD  - Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization 
      Center, University of Kansas, Lawrence, KS 66047, United States.
FAU - Kumru, Ozan S
AU  - Kumru OS
AD  - Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization 
      Center, University of Kansas, Lawrence, KS 66047, United States.
FAU - Smith, Lee
AU  - Smith L
AD  - GreyRigge Associates Limited, UK.
FAU - Nelson, Paul
AU  - Nelson P
AD  - PRISM Training and Consultancy Limited, UK.
FAU - Joshi, Sangeeta B
AU  - Joshi SB
AD  - Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization 
      Center, University of Kansas, Lawrence, KS 66047, United States.
FAU - Livengood, Jill A
AU  - Livengood JA
AD  - Takeda Vaccines Inc., Cambridge, MA 02139, United States. Electronic address: 
      jill.livengood@takeda.com.
FAU - Volkin, David B
AU  - Volkin DB
AD  - Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization 
      Center, University of Kansas, Lawrence, KS 66047, United States. Electronic 
      address: volkin@ku.edu.
LA  - eng
PT  - Journal Article
DEP - 20170512
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Excipients)
RN  - 0 (Vaccines, Attenuated)
RN  - 0 (Viral Vaccines)
SB  - IM
MH  - Excipients/*chemistry
MH  - Flavivirus
MH  - Freeze Drying
MH  - Vaccines, Attenuated/*chemistry
MH  - Viral Vaccines/*chemistry
OTO - NOTNLM
OT  - Dengue
OT  - Design of experiments
OT  - Excipients
OT  - Flavivirus
OT  - Formulation
OT  - Live attenuated vaccine
OT  - Lyophilization
OT  - Stability
OT  - Vaccine
OT  - Virus
EDAT- 2017/05/17 06:00
MHDA- 2019/02/02 06:00
CRDT- 2017/05/17 06:00
PHST- 2016/12/23 00:00 [received]
PHST- 2017/04/17 00:00 [revised]
PHST- 2017/04/24 00:00 [accepted]
PHST- 2017/05/17 06:00 [pubmed]
PHST- 2019/02/02 06:00 [medline]
PHST- 2017/05/17 06:00 [entrez]
AID - S0264-410X(17)30602-3 [pii]
AID - 10.1016/j.vaccine.2017.04.086 [doi]
PST - ppublish
SO  - Vaccine. 2018 May 24;36(22):3169-3179. doi: 10.1016/j.vaccine.2017.04.086. Epub 
      2017 May 12.