Inhibition of Aggregation of Aluminum Hydroxide Adjuvant During Freezing and Drying

Selection of Adjuvants for Enhanced Vaccine Potency

“…Freeze-thawing (to -40C) of 0.2% Alhydrogel at pH 4.0 caused particle aggregation, which is inversely related to the cooling or thawing rate [61]. Freeze-thawing of aluminum hydroxycarbonate gel caused coagulation, leading to formation of visible aggregates without changing the point of zero charge [62].…”

“…The protective effect seems attributable to their general lyoprotective effect rather than reduction in freezing temperature. Other excipients are also found to be effective in inhibiting freezing-reduced aggregation, such as adsorbable polymers or surface-active agents [62], and trehalose [61].…”

“…It has been shown that freeze-drying of 0.2% Alhydrogel caused particle aggregation with bigger median diameter than that caused by the freeze-thawing process alone [61]. Lyophilization of a model antigen, bovine intestinal alkaline phosphatase adsorbed on aluminum hydroxide, induced adjuvant aggregation and reduced the antigen's enzymatic activity (up to 50% drop in activity) [65].…”

Influence of Formulation pH and Suspension State on Freezing-Induced Agglomeration of Aluminum Adjuvants

“…[1][2][3][4][5] Most of the published findings on freezethawing of aluminum adjuvant suspensions focused on aluminum-hydroxycarbonate-or aluminumhydroxide-containing suspensions at one pH without a clearly specified settlement state for the suspension. 3,4 We hypothesize that the state of a suspension (dispersed, flocculated, settled) that is influenced by both the magnitude of the zeta potential of aluminum adjuvant (or vaccine) particles and the formulation pH will influence aggregation damage from freeze-thaw. To further our knowledge in this area, we studied the effect of freeze-thawing of two aluminum adjuvants (Alhydrogel TM and Adjuphos TM ) at three pH levels (4, 6.5, and 7.2).…”

Self‐Healing Microencapsulation of Biomacromolecules without Organic Solvents

“…[20] We investigated similar active loading strategies with two vaccine antigens (ovalbumin (OVA) and tetanus toxoid (TT)). OVA or TT protein antigens were loaded into SM PLGA containing lyophilization-stabilized Al(OH) 3 adjuvant [21] (ASM, Table S1 in Supporting Information), which absorbed and stabilized the antigen in the polymer matrix from surrounding 0.5-1 mg/mL antigen solution, with up to 87-98 % EE and 1.0-1.6 % OVA (ASM-3, Tables S3 and S4 in Supporting Information) and TT (ASM-2, Table S5 in Supporting Information). Extent of self-healing of polymer pores was also easily enhanced by addition of common plasticizers, e.g., diethyl phthalate (DEP) ( Figure S4, Supporting Information).…”