Heat-stable measles vaccine produced by spray drying.
A combination of unique stabilizers and mild spray drying process conditions was employed to produce heat-stable measles vaccine powder. Live attenuated measles vaccine from Serum Institute of India was formulated with pharmaceutically approved stabilizers, including sugars, proteins, amino acids, polymers, surfactants, and plasticizers, as well as charged ions. In addition, the effects of buffer salt and pH on the storage stability of measles virus were examined. The potency of the dried vaccine stored at several temperatures was quantified by TCID(50) assay on Vero cells. As a comparison to other process methods, lead formulations were also subjected to freeze drying and foam drying. The optimized measles vaccine formulation tested at 37 degrees C was stable for approximately 8 weeks (i.e. time for 1 log TCID(50) loss). The measles titer decreased in a bi-phasic manner, with initial rapid loss within the first week but relative stability thereafter. Key stabilizers identified during the formulation screening processes were L-arginine, human serum albumin, and a combination of divalent cations. Spray drying was identified as the optimal processing method for the preparation of dried vaccine, as it generally resulted in negligible process loss and comparable, if not better storage stability, with respect to the other processes. Processing methods and formulation components were developed that produced a measles vaccine stable for up to 8 weeks at 37 degrees C, which surpassed the WHO requirement for heat stability of 1 week at that temperature.
Ohtake
Satoshi
S
Aridis Pharmaceuticals, 5941 Optical Court, San Jose, CA 95138, USA.
Martin
Russell A
RA
Yee
Luisa
L
Chen
Dexiang
D
Kristensen
Debra D
DD
Lechuga-Ballesteros
David
D
Truong-Le
Vu
V
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D002522:Chlorocebus aethiops; D004355:Drug Stability; D005612:Freeze Drying; D006358:Hot Temperature; D006801:Humans; D008458:Measles Vaccine / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D014709:Vero Cells
D008458:Measles Vaccine; D012709:Serum Albumin; D001120:Arginine