Chapter 27
Thin-Film Freeze-Drying Is a Viable Method to Convert
Vaccines Containing Aluminum Salts from Liquid to Dry
Powder
Riyad F. Alzhrani, Haiyue Xu, Chaeho Moon, Laura J. Suggs,
Robert O. Williams III, and Zhengrong Cui
Abstract
Aluminum salts are used as an adjuvant in many human and veterinary vaccines. However, aluminum saltadjuvanted vaccines are sensitive to temperature change and must be stored at 2–8
C. Inadvertently
exposing them to slow freezing temperatures can cause irreversible aggregation of aluminum salt microparticles and loss of potency and/or immunogenicity of the vaccines. There have been efforts to overcome
this limitation by either adding stabilizing agents to the liquid vaccine or converting the vaccine from a
liquid to a dry powder. Thin-film freeze-drying (TFFD) has proven to be an effective process to convert
aluminum salt-adjuvanted vaccines from liquid to dry powder without causing particle aggregation or loss
of immunogenicity upon reconstitution. This chapter provides a review of the TFFD process and examples
for preparing stable aluminum salt-adjuvanted vaccine dry powders using TFFD.
Key words Aluminum salts, Vaccine, Thin-film freezing, Lyophilization, Dry powder
1 Introduction
Insoluble aluminum salt-adjuvanted vaccines make up more than
half of the vaccines approved for human use [1–3]. Vaccines including hepatitis B, human papillomavirus, and diphtheria–tetanus–
pertussis vaccines are adjuvanted with aluminum salts [2–4]. The
World Health Organization (WHO) recommends that all vaccines
(a total of 16), except oral polio vaccine, must to be stored at
2–8
C, especially the ones containing aluminum salts [5]. Aluminum salt-adjuvanted vaccines are known to be sensitive to slow
freezing [5]. Vaccines adjuvanted with aluminum salts are suspensions of aluminum salt microparticles with antigens adsorbed on
them [6]. When aluminum salt-adjuvanted vaccines are exposed to
freezing temperatures, the aluminum salt particles aggregate, and
the extent of aggregation is dependent on parameters such as the
Blaine A. Pfeifer and Andrew Hill (eds.), Vaccine Delivery Technology: Methods and Protocols, Methods in Molecular Biology,
vol. 2183, https://doi.org/10.1007/978-1-0716-0795-4_27, © Springer Science+Business Media, LLC, part of Springer Nature 2021
489
Thin-Film Freeze-Drying Is a Viable Method to Convert
Vaccines Containing Aluminum Salts from Liquid to Dry
Powder
Riyad F. Alzhrani, Haiyue Xu, Chaeho Moon, Laura J. Suggs,
Robert O. Williams III, and Zhengrong Cui
Abstract
Aluminum salts are used as an adjuvant in many human and veterinary vaccines. However, aluminum saltadjuvanted vaccines are sensitive to temperature change and must be stored at 2–8
C. Inadvertently
exposing them to slow freezing temperatures can cause irreversible aggregation of aluminum salt microparticles and loss of potency and/or immunogenicity of the vaccines. There have been efforts to overcome
this limitation by either adding stabilizing agents to the liquid vaccine or converting the vaccine from a
liquid to a dry powder. Thin-film freeze-drying (TFFD) has proven to be an effective process to convert
aluminum salt-adjuvanted vaccines from liquid to dry powder without causing particle aggregation or loss
of immunogenicity upon reconstitution. This chapter provides a review of the TFFD process and examples
for preparing stable aluminum salt-adjuvanted vaccine dry powders using TFFD.
Key words Aluminum salts, Vaccine, Thin-film freezing, Lyophilization, Dry powder
1 Introduction
Insoluble aluminum salt-adjuvanted vaccines make up more than
half of the vaccines approved for human use [1–3]. Vaccines including hepatitis B, human papillomavirus, and diphtheria–tetanus–
pertussis vaccines are adjuvanted with aluminum salts [2–4]. The
World Health Organization (WHO) recommends that all vaccines
(a total of 16), except oral polio vaccine, must to be stored at
2–8
C, especially the ones containing aluminum salts [5]. Aluminum salt-adjuvanted vaccines are known to be sensitive to slow
freezing [5]. Vaccines adjuvanted with aluminum salts are suspensions of aluminum salt microparticles with antigens adsorbed on
them [6]. When aluminum salt-adjuvanted vaccines are exposed to
freezing temperatures, the aluminum salt particles aggregate, and
the extent of aggregation is dependent on parameters such as the
Blaine A. Pfeifer and Andrew Hill (eds.), Vaccine Delivery Technology: Methods and Protocols, Methods in Molecular Biology,
vol. 2183, https://doi.org/10.1007/978-1-0716-0795-4_27, © Springer Science+Business Media, LLC, part of Springer Nature 2021
489