Aluminum hydroxide adjuvant

Alhydrogeh, aluminium hydroxide adjuvant aluminium oxy-hydroxide poorly crystalline boehmite pseudoboehmite Rehydragel. 

Aluminum hydroxide adjuvant is used in parenteral human and veterinary vaccines. It activates Th2 immune responses, including IgG and IgE antibody responses. It is also used for the isolation of certain serum components such as blood clotting factors.  

Particle size distribution primary particles are fibrous with average dimensions of 4.5 x 2.2 x lOnm. The primary particles form aggregates of 1-10 pm. 

Solubihty soluble in alkali hydroxides and mineral acids. Heat may be required to dissolve the aluminum hydroxide adjuvant. 

X-ray diffractogram exhibits characteristic x-ray diffraction pattern having diffraction bands at 6.46, 3.18, 2.35, 1.86, 1.44 and 1.31 A. 

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Table I Pharmacopeial specifications for aluminum hydroxide adjuvant.

Aluminum hydroxide adjuvant is stable for at least two years when stored at 4—30°C in well-sealed inert containers. It must not be allowed to freeze as the hydrated colloid structure will be irreversibly damaged. 

Aluminum hydroxide adjuvant is a white hydrogel that sediments slowly and forms a clear supernatant. 

When exposed to phosphate, carbonate, sulfate, or borate anions, the point of zero charge for aluminum hydroxide adjuvant decreases. 

Aluminum hydroxide adjuvant is prepared by the precipitation of a soluble aluminum salt by an alkali hydroxide, or the precipitation of an alkali aluminate by acid. 

Different grades of aluminum hydroxide adjuvant with various concentrations, protein binding capacities, and points of zero charge are available. 

Johnston CT, Wang JL, Hem SL. Measuring the surface area of aluminum hydroxide adjuvant. / Pharm Sci 2002 91 1702-1706. 

Table 2 lists various types of biopharmaceutical products from animal cell cultures. Viral vaccines are usually produced by first culturing the host cells (e.g., MRC-5 and WI-38) to form a cell layer on the surface of substratum. Seed virus is then added and incubated for about 3 weeks for replication in the host cells without killing them. After washing to remove the medium components, the cells are lysed to release the virions for harvesting and purification. The inactivated viral vaccine is produced by inactivation with formaldehyde and adsorption onto aluminum hydroxide adjuvant. 

Wittayanukulluk, A. et al.. Effect of microenvuonment pH of aluminum hydroxide adjuvant on the chemical stability of adsorbed antigen, Vaccine. 22, 1172, 2004. 

Diffuse reflectance spectroscopy was used to screen the possible interactions between a large number of adjuvants and several dyes [23]. It was concluded that supposedly inert excipients (such as starch or lactose) were capable of undergoing significant reactions with the dyes investigated (Red No. 3, Blue No. 1, and Yellow No. 5). For adjuvants containing metal ions (zinc oxide, or calcium, magnesium, and aluminum hydroxides), the degree of interaction could be considerable. It was concluded from these studies that dye-excipient interactions could also be responsible for the lack of color stability in certain tablet formulations. 

Kreuter and Speiser [77] developed a dispersion polymerization producing adjuvant nanospheres of polymethylmethacrylate) (PMMA). The monomer is dissolved in phosphate buffered saline and initiated by gamma radiation in the presence and absence of influenza virions. These systems showed enhanced adjuvant effect over aluminum hydroxide and prolonged antibody response. PMMA particles could be distinguished by TEM studies and the particle size was reported elsewhere to be 130 nm by photon correlation spectroscopy [75], The particle size could be reduced, producing monodisperse particles by inclusion of protective colloids, such as proteins or casein [40], Poly(methylmethacrylate) nanoparticles are also prepared... 

Very often, vaccines are formulated with certain substances to enhance the immune response. These substances are called adjuvants (from the Latin adju-vare, which means to help ). The most common adjuvants for human use are aluminum hydroxide, aluminum phosphate, and calcium phosphate. Other adjuvants being used include bacteria and cholesterol. Mineral oil emulsions are normally the adjuvants used in animal studies. The adjuvant known as Freund s complete adjuvant consists of killed tubercle bacilli in water-inmineral oil emulsion, and Freund s incomplete adjuvant is a water-in-oil emulsion. Both these adjuvants are effective in stimulating an immune response, but they cause unacceptable side effects in humans (see Table 4.2). 

Very often whole-killed vaccines are formulated with adjuvants, which are designed to enhance vaccine persistence and induction of immune responses. However, the only adjuvant currently approved by FDA for clinical use is alum, in the form of vaccines complexed with aluminum hydroxide or aluminum sulfate. Even with the help of alum adjuvants, inactivated vaccine antigens are presented to APC extracellularly, as opposed to intracellularly, leading to a bias toward antibody-mediated responses. Little or no cell-mediated response to whole-killed vaccines with alum adjuvant renders some vaccines ineffective. 

Following intramuscular administration of aluminum hydroxide or aluminum phosphate vaccine adjuvants in rabbits, increased levels of26Al were found in the kidney, spleen, liver, heart, lymph nodes, and brain (in decreasing order of aluminum concentration) (Flarend et al. 1997). 

Kato H, Shibano M, Saito T, et al. 1994. Relationship between hemolytic activity and adsorption capacity of aluminum hydroxide and calcium phosphate as immunological adjuvants for biologicals. Microbiol Immunol 38 543-548. 

Aluminum, in the form of aluminum hydroxide, aluminum phosphate or aluminum potassium sulfate, is used as adjuvant in various vaccine formulations to elicit an increased immunogenic response. 

Aluminum adjuvants in human vaccines are either aluminum hydroxyphosphate (commonly referred to as aluminum phosphate) or aluminum oxyhydroxide (aluminum hydroxide). Aluminum-based vaccines are prepared by adsorption of antigen to commercial aluminum hydroxide or aluminum phosphate gels or by mixing antigen with alum (potassium aluminum sulfate),... 

Jankovic, D. Caspar, P. Zweig, M. Garcia-MoU, M. Showalter, S.D. Vogel, F.R. Sher, A. Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant for antibody as well as type 1 cytokine responses to HIV-1 GP120. J. Immunol. 1997,159, 2409-2417. 

The aluminum hydroxide gel referred to in the USP 28 is used in cosmetics as an emollient, filler, humectant, a mild astringent, and viscosity controlling agent. In pharmaceutical preparations it is used as an adsorbent, and as a protein binder. It is also used therapeutically as an antacid, and as an abrasive in dentrifrices. It is not, however, used as a vaccine adjuvant. 

Aluminum phosphate adjuvant is formed by the reaction of a solution of aluminum chloride and phosphoric acid with alkali hydroxide. 

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